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 INDEX

VOLUME 48 • NUMBER 1 • 2021

Original articles
The Impact of Visceral Adipose Tissue on the Severity of Anxiety and Depression ................................................ 1
Sengul Kocamer Sahin, Bahadır Demir, Gülcin Elboga, Abdurrahman Altındağ, Ünzile Meryem Atalay, Ayşegül Şahin Ekici,

The relationship between childhood traumas and stressors of recent year with suicide attempt and general
health in adulthood................................................................................................................................................................. 6
Hourivash Ghaderi, Mohsen Khosravi, Ali Hasanpour Dehkordi,

Brief Symptom Inventory: reporting Brazilian populational parameters during COVID-19 pandemics ............... 12
Alexandre Luiz de Oliveira Serpa, Debora Marques de Miranda, Danielle de Souza Costa, Jonas Jardim de Paula, Mayra Isabel
C. Pinheiro, Alexandre Paim Diaz, Antônio Geraldo Silva, Leandro Fernandes Malloy-Diniz

Increased serum nesfatin-1 levels among adolescents diagnosed with major depressivebdisorder ................. 16
S. Burak Acikel, Esra Hosoglu, Abdulbaki Artik, Fatma Humeyra Yerlikaya Aydemir

Comparison of prolactin level in schizophrenia patients treated with risperidone oral or long-acting injections
– preliminary report ............................................................................................................................................................... 20
Anna Skowrońska, Dominik Strzelecki, Adam Wysokiński

Relationship between mobile phone addiction and Narcissistic personality disorder among medical students ...
................................................................................................................................................................................................... 24
Roya Vaziri-Harami, Fatemeh Heidarzadeh, Ali Kheradmand

Personality, cognitive emotion regulation and insomnia............................................................................................... 29

Ana Paula Amaral, Sandra Carvalho Bos, Maria João Soares, Ana Telma Pereira, Mariana Marques, Nuno Madeira, Vasco
Nogueira, Miguel Bajouco, António Macedo

Religiosity/spirituality, motivation and self-efficacy in the treatment of crack users ............................................ 36

Amanda Ely, Bruno Paz Mosqueiro

Personality structure evaluation: differences between clinical and non-clinical samples using the Inventory of
Personality Organization (IPO) .......................................................................................................................................... 45
Carolina Rabello Hessel, Sergio Eduardo Silva Oliveira, Vânia Silva Lugo, Vanessa Volkmer, Rochelle Affonso Marquetto

Factors influencing self-esteem in Tunisian adolescents with prosocial behavior ............................................... 51

Charfi Nada, Kammoun Wiem, Maâlej Bouali Manel, Omri Sana, Feki Rim, Smaoui Najeh, Zouari Lobna, Moalla Yosr, Ben
Thabet Jihene, Maâlej Mohamed

Review articles
Pharmacologic Treatment of Antidepressant-Induced Excessive Sweating: A SystematicReview ... 57
Summer R. Thompson, Laura E. Compton, Min-Lin Fang, Jyu-Lin Chen

Brief reports
Prophylactic laxatives in clozapine-treated patients: a long road ahead ................................................................ 66
Raúl Alberto Estevez-Cordero, Teresa Morera-Herreras, Rafael Hernandez, Juan Medrano, Susanna Every-Palmer, Unax
Lertxundi
Letter to the editor
Exacerbation of anxiety symptoms in the setting of COVID-19 pandemic: An overview and clinically-useful
recommendations ................................................................................................................................................................ 69
Gustavo C Medeiros, Scott R. Beach

Plasma paroxetine level is independent of the change in plasma interleukin-6 level in remitted patients with
major depressive disorder ................................................................................................................................................. 71
Reiji Yoshimura, Naomichi Okamoto, Yuki Konishi, Atsuko Ikenouchi

Opercular syndrome in childhood with manic symptoms: a case report ................................................ 73

Lee Fu-I, Miguel Angelo Boarati, Gustavo Nogueira Lima
 Original article

The Impact of Visceral Adipose Tissue on the Severity of Anxiety and Depression
Sengul Kocamer Sahin*
https://orcid.org/0000-0002-5371-3907
Bahadır Demir
https://orcid.org/0000-0003-2798-6255
Gülcin Elboga
https://orcid.org/0000-0003-3903-1835
Abdurrahman Altındağ
https://orcid.org/0000-000-5531-4419
Ünzile Meryem Atalay
https://orcid.org/0000-0001-5623-2351
Ayşegül Şahin Ekici
https://orcid.org/0000-0001-5788-1484

Gaziantep University, Faculty of Medicine, Department of Psychiatry, Gaziantep, Turkey

Received: 02-05-2020 – Accepted: 01-10-2020

DOI: 10.1590/0101-60830000000269

ABSTRACT
Background: There is a reciprocal relationship between psychopathologies and visceral adiposity. A few studies reviewed the relationship
between visceral adiposity and major depressive disorder (MDD) and/or particularly anxiety disorders (ADs).
Objective: This study aimed to investigate the relationship between dysfunctional visceral adipose tissue (VAT) and severity of anxiety/
depression in two patient groups diagnosed with MDDs and ADs that are non-responders to antidepressants.
Methods: The Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS) were used for the assessment.
This cross-sectional study included 89 patients, of which 44.9% had MDD, and 55.1% had ADs and 40 healthy individuals as control group.
VAT was calculated using the visceral adiposity index (VAI) formula.
Results: Although VAI was significantly higher in patients with MDD than control group (p=0.008), there was no difference between
patients with ADs and the control group (p=0.072). There was a positive correlation between VAI and HDRS in patients with MDD (P =
0.034 r: 0.336), while there was no significant correlation between VAI and HARS in patients with ADs. Multiple regression analysis revealed
significant associations between HDRS and VAI after adjusting for age, gender, and educational levels (P = 0.042).
Conclusion: This study suggests that VAT, which may have an important role in the physiopathology and severity of depression in patients
with MDD, may not play a similar role in the physiopathology and severity of anxiety in patients with ADs.

Sahin SK / Arch Clin Psychiatry. 2021;48(1):01-05.

Keywords: Visceral adiposity, anxiety, depression

Introduction which is calculated using the waist circumference, body mass

Major depressive disorder (MDD) and anxiety disorders (ADs)
and are the most prevalent psychiatric disorders associated with
a high burden of disease. ADs are classified as panic disorder,
agoraphobia, generalized AD, social AD, selective mutism, specific
phobias, and separation AD, according to the DSM-51. In patients
with any of the ADs, anxiety is excessive and unreasonable and
also disproportionate to the real danger posed by the situation (1).
MDD is defined as the presence of five of the following criteria: not
enjoying life for a period of at least two weeks, depression, fatigue,
psychomotor retardation, changes in sleep patterns and appetite,
thoughts of self-worthlessness, distraction, and suicidal thoughts
according to the DSM-52.
Increased visceral adipose tissue (VAT) is a risk indicator for
cardiovascular diseases, metabolic disorders, malignancy, and
visceral adipose dysfunction (VAD) that appears to be associated
with cardiometabolic risks3-5. The visceral adiposity index (VAI),
index (BMI), and lipid values for VAT analysis, is developed to
calculate the dysfunctional VAT of an individual and was found to
be significant in the risk assessment for cardiovascular diseases3-5.
This scale can be considered as a simple VAD indicator that assesses
cardiometabolic risk. VAT may also be increased in patients with
normal weight; therefore, it may help with early diagnosis and
could protect the patient with regard to the metabolic syndrome
that is considered as the cause of obesity6.
VAT secretes cytokines and adipokines and creates a pro-
inflammatory condition in obesity7,8. Some of these secreted factors
are also considered as potential factors for some mental disorders8.
For example, inflammatory genes in the VAT were found to be
significantly higher in patients with anxiety or mood disorders than
in subjects without mental disorders9. Although there have been
numerous studies about the relationship between increased visceral
adiposity and schizophrenia and/or mood disorder10,11, there are few
studies that reviewed the relationship between visceral adiposity

Address for correspondence: Sengül Sahin, Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey; Fax: +90 (342) 360 60 60; , E-mail: snglkcmr@hotmail.com
2 Sahin SK / Arch Clin Psychiatry. 2021;48(1):01-05
and major depression and/or particularly Ads12,13; however, the
reciprocal relationship between these psychopathologies and
visceral adiposity is not fully understood. In the general population,
overall and abdominal adiposity measurements were found to be
associated with a depressive mood14 Increased BMI was speculated
to lead to anxiety, which is found to be more frequently in obese/
overweight people15. Another issue is the lack of response to
treatments for depression and/or anxiety in overweight patients.
Studies confirmed the significance of body weight and BMI in
treating MDD16. For example; a study found that a greater body
weight without obesity predicted the lack of response to fluoxetine
which is selective serotonin reuptake inhibitor17. So, increased
visceral adiposity may be a reason for this unresponsiveness.
This study aims to analyze 1) VAI in patients with MDD and
ADs and 2) the relationship between anxiety/depression and VAI
in two groups of patients with MDDs and ADs who are non-
responders to SSRI/SNRI to determine if high VAI is associated
with non-response to treatment in MDDs and/or ADs.
METHODS
In this study, we compared three groups; patients with ADs, patients
with MDD, and healthy individuals. We compared the difference
between groups in terms of dysfunctional visceral adipose tissue
using VAI. We also examined the relationships between the severity
of depression and VAI in patients with MDD and between the
severity of anxiety and VAI in patients with ADs.
Study population
Patients admitted to the psychiatry outpatient clinic at the Gaziantep
University Faculty of Medicine, Gaziantep, Turkey diagnosed with
MDD or ADs according to the DMS 5 were included in this cross-
sectional study. The diagnosis for MDD and ADs was made by two
psychiatrists. Of the 89 patients, 44.9% had MDD, and 55.1% had
ADs. Of the 49 patients with ADs, 24 had generalized AD, six had
panic disorder, four had social AD, and 15 had unspecified AD. Of
the 40 patients with MDD, 40% were males, 65% were married, and
their mean age was 43.4 ± 14.5. Of the 49 patients with ADs, 20.4%
were males, 77.6% were married, and their mean age was 36.1 ± 13.2
(Table 1). The control group was selected from a total of 40 healthy
individuals who came to the hospital for general screening after
applying to the Health Commission to get a clean bill of health in
the preceding 6 months and who were found to have no disabilities.
The study was approved by the Clinical Trials Ethics Committee of
Gaziantep University. All participants filled out a written consent
form. Non-response is described as a less than 50% improvement
in the total score of a commonly used anxiety rating scale or a non-
response to an adequate dose of first-line pharmacological Selective
serotonin reuptake inhibitor SSRI/ serotonin noradrenalin
reuptake inhibitors (SNRI) treatment for 4–6 weeks, compatible
with previous studies18.
Procedure
In this study, we compared three groups; patients with ADs, patients
with MDD, and healthy individuals. We compared the difference
between groups in terms of dysfunctional visceral adipose tissue
using VAI. We also examined the relationships between the severity
of depression and VAI in patients with MDD and between the
severity of anxiety and VAI in patients with ADs.
The metabolic parameters of the patients were monitored every
six months in the outpatient clinic for anxiety and mood disorders.
After determining the patients, the required new parameters and
results were recorded for 6 months. Patients with severe neurological
diseases, diabetes mellitus, and other endocrinopathies, liver
disease, malignant diseases, mental retardation, alcohol, substance
use disorder, or a history of addiction were not included in the study.
Anxious depressions were also excluded so that the results are not
affected. In addition, we used the Hamilton Depression Rating Scale
(HDRS) and the Hamilton Anxiety Rating Scale (HARS) in both
patient groups. We excluded patients with an anxiety score above 7
for the MDD group and those with a depression score above 7 for
the ADs group. The sociodemographic data of all patients, such as
age and gender, were recorded.
Assessment Tools
Visceral Adiposity Index (VAI)
The heights and weights of each subject were measured using the
same calibrated weight scale with bare feet and light clothing. The
waist circumference of subjects was measured at the middle level
between the inferior costal margin and the upper iliac crest while
they were standing. Peripheral venous blood samples were obtained
after 12 hours of fasting, and the blood samples were analyzed on
the same day. High-density lipoprotein (HDL) and triglyceride
(TG) were analyzed using the spectrophotometric method on a
Beckman device.
The VAI of female patients was calculated with the Waist
circumference / [36.58 + (1.89 x BMI)] x (TG / 0.81) x (1.52 / HDL)
formula, while the Waist circumference / [39.68 + (1.88 x BMI)]
x (TG / 1.03) x (1.31 / HDL) formula was used in male patients3,5.
Hamilton Depression Ratind Scale (HDRS)
The HDRS, developed by Hamilton in 1960, measures the level and
severity of depression in the patient19. It consists of 21 items. Items
on the HDRS scale are marked between 0–4 and 0–2. The Turkish
validity and reliability study was done by Akdemir et al. in 199620.
Hamilton Anxiety Rating Scale (HARS)
This is a rating scale developed to measure the severity of anxiety
symptoms. It was developed by Hamilton to determine the level
of anxiety and symptom distribution in individuals21. The Turkish
validity and reliability study was performed by Yazıcı et al22.
Statistical Analysis
Descriptive statistics were used to evaluate the demographic
characteristics with the data acquired from the 49 patients with
MDD and 40 patients with ADs. The Chi-square test was used in
the comparison of categorical variables. Kruskal–Wallis followed by
post hoc tests uses to compare groups. Multiple regression analysis
was performed to correct the effect of age, gender, and education on
the severity of anxiety/depression. Windows version of SPSS 22.0
package software was used in the analyses. P < 0.05 was considered
as significant.
RESULTS
There were no significant differences between groups in terms of
age, sex, marital status and education. Patients’ sociodemographic
data is shown in Table 1. The most used drug in both patient groups
was Sertraline followed by paroxetine, fluoxetine and others. Table
2 shows the distribution of drugs that patients in both groups used.
The HDRS total score mean value was determined as 25.25 + 7.95
for patients with MDD. The HARS total score mean value was
determined as 21.14 + 5.75 for patients with ADs. The VAI score
mean value was determined as 8.18 ± 8.46 for patients with MDD
and 4.90 ± 2.85 for patients with ADs. There were significant
differences between groups in terms of Thyrigliceride levels and
VAI. When we examined the ADs and MDD groups in post hoc
 Sahin SK / Arch Clin Psychiatry. 2021;48(1): 01-05 3

analysis, we found that there was no difference between patients
with ADs and the control group in terms of VAI (0.072). However
VAI was significantly higher in patients with MDD than control
group (p=0.008). There was no difference between ADs and MDD
(0.068). Also Thyrigliceride level was higher both in patient groups
with MDD (p=0.012) and ADs (p=0.010) than control. Table 3
shows the metabolic parameters that use the VAI formulation in
both patient groups and control group.
There was a positive correlation between VAI and HDRS in
patients with MDD (P = 0.034 r: 0.336), whereas there was no
significant correlation between VAI and HARS in patients with
ADs (P = 0.610 r: −0.075).
BMI classified as normal weight (BMI 19 - <25 kg/m2),
overweight (BMI 25 - <30 kg/m2) and obese (BMI ≥30 kg/m2). 59
% (29/49) patients with ADs had a normal weight.
In the multiple linear regression analysis model for MDD and
ADs, ANOVA results were p = 0.05 and p = 0.88, respectively. Age
and VAI were found to be statistically significant factors influencing
the HDRS. Multiple regression analysis revealed significant
associations between HDRS and VAI after adjusting for age, gender,
and educational levels (p = 0.042) (Table 4).

Table 1: Sociodemographic data of Patients

MAJOR ANXIETY CONTROL P
DEPRESSIVE DISORDERS
DISORDER
Male 16 (40%) 10 (20.4%) 13(20.4%)
Sex 0.12
Female 24 (60%) 39 (79.6%) 27 (67%)
Age 43.4±14.5 36.1±13.2 37.1±0.89 0.051
Education (years) 8.9±3.2 9.4±3.3 9.49±2.3 0.78
Single 14 (%35) 11 (%22.4) 7(17%)
Marital Status 0.84
Married 26 (%65) 38 (%77.6) 33(83%)

Table 2: Pharmacotherapy data of patients

MAJOR DEPRESSIVE DISORDER ANXIETY DISORDERS
Frequency Percent Frequency Percent
Fluoxetine 6 15,0 7 14,3
Sertraline 13 32,5 16 32,7
Escitalopram 3 7,5 11 22,4
Citalopram 2 5,0 2 4,1
Valid Paroxetine 7 17,5 8 16,3
Duloxetine 3 7,5 2 4,1
Venlafaxine 3 7,5 2 4,1
Vortioxetine 3 7,5 1 2,0
Total 40 100,0 49 100,0

Table 3: Metabolic parameters that use in VAI formulation and VAI mean scores of Patients and Control group
MAJOR DEPRESSIVE ANXIETY DISORDERS Control p
DISORDER
HDL mg/dL 45.79±14.81 49.10±10.38 51.8±8.6 0.164
Thyrigliceride mg/dL 168.66±135.27 133.40±65.86 102.5±23.8 0.028*
VAI 8.18 ± 8.46 4.90±2.85 3.85±1.33 <0.001*
*p<0.05

Table 4: Linear Regression Model for Prediction of HamD Scores in Patients with MDD
Variable B %95 CI p
VAI 0.315 0.011 0.581 0.042*
Age 0.350 0.015 0.427 0.036*
Sex -0.192 -8.25 2.11 0.237
Education -0.097 -0.990 0.52 0.534
CI: Confidence interval, B Standardized coefficient for the constant*p<0.05
:
4 Sahin SK / Arch Clin Psychiatry. 2021;48(1):01-05
DISCUSSION
In this study, the relationships between depression/anxiety
symptom levels and VAI were examined for patients with MDD
and ADs who are non-responders to first-line SSRI/SNRI. First we
found that VAI was higher in patients with MDD not in Patients
with ADs than controls. While there was no significant correlation
between VAI and anxiety scores in patients with ADs, there was a
positive significant correlation between VAI and depression scores
in patients with MDD.
In the regression analysis, it was determined that VAI
predicted the severity of depression according to the HDRS
scale. In similar studies; Rose et al. found a strong association
between depressive symptoms and VAT in middle-aged women23.
Lee et al. found that depressive mood is associated with VAT in
overweight premenopausal women. However, in both studies, the
participants did not suffer from MDDs. Coryell et al. found that
MDD was associated with increased fat mass among overweight/
obese adolescences (24), and Alshehri et al. found that measures
of adiposity were associated with a depressive mood in a graded
fashion14. Our study supports those findings in patients with MDD
who are non-responders to SSRI/SNRI. Similarly, Papakostas et al.
found that a greater body weight without obesity predicted non-
response to SSRI17.
In our study, the significance of visceral adiposity in mood
disorders such as major depression is, again, noticeable. How might
visceral adiposity contribute to the severity of depression? VAT
and mood disorders are interconnected with the inflammation of
the biological roots of depression25. As there are too many studies
that support the subclinical inflammation in mood disorders,
many studies found higher levels of obesity, abdominal obesity,
metabolic syndrome, and BMI which are related to increased
visceral adiposity in patients with mood disorders9,14,26. Also higher
Thyrigliceride level in patients with MDD may be contributed
metabolic breakdown. These results are not surprising, considering
VAT secretes cytokines and adipokines and may be creating a pre-
inflammatory condition in mood disorders. Another issue is that
depression may lead to an increase in VAT. Depression often causes
an increase in cortisol, and this chronic stimulation can lead to an
increase in VAT.
There were no significant differences between patients with
ADs and control group in terms of VAI scores, and there was no
association between VAI and anxiety scores in patients with ADs.
A meta-analysis by Amiri showed a higher frequency of anxiety
in obese/overweight groups than normal weight in terms of
some subgroups (sex, obesity and anxiety assessment, adjusted/
unadjusted, anxiety duration and age)15. Anxiety was found to
be associated with excess adiposity when controlling for other
emotional factors as depression and hostility/anger27. Diagnoses
of social phobia, panic disorder, or dysthymia were found to
have led to significantly increased weight circumferences and/
or BMI in boys28. Hillman et al. found that symptoms of anxiety
were associated with percentage body fat among adolescent
females using another objective measure of adiposity with body fat
percentage using dual-energy X-ray absorptiometry. In our study,
no significant relationship was observed in the measurement of
patients’ adiposity diagnosed with ADs, unhealthy adolescents/
adults, or non-obese groups. However, in our study, most of the
patients (29/49) with ADs had a normal weight (BMI: 19−25). Low
numbers of obese or overweight patients may have affected the
results.
The most important limitations of this current study are the
small number of patients and the lack of control groups with a
similar number of subjects. Since the VAI values of the patients
were not known before drug treatment, the change after treatment
with antipsychotics is not known. Another limitation of this study
is the lack of data on the illness duration and all the treatment
history of patients enrolled in our study to clarify the effects on
the severity of symptoms. Anxiety is frequently comorbid with
depression; therefore, we could not assert that patients with MDD
had no anxiety symptoms.
Conclusion
In conclusion, it was observed that there was a positive relationship
between VAI and depression severity in patients with MDD who
did not respond to SSRI and/or SNRI treatment, but there was no
similar relationship between anxiety symptom severity and VAI in
patients with ADs. It may be thought that VAT, which may have an
important role in the physiopathology and severity of depression,
may not play a similar role in the physiopathology and severity
of anxiety in patients with ADs. Large-scale prospective studies
are needed to clarify the relationship between depression/anxiety
severity and VAT and their relationship with the response to
treatment.
Conflict of Interest Statement
There is no conflict of interest
Acknowledgements
Authors would like to thank Enago for English language review
All of the authors declare that there are no conflicts of interest in
connection with this paper. Authors would like to thank Enago for
English language review.
REFERENCES
1. Bandelow B. Comparison of the DSM–5 and ICD–10: panic and other
anxiety disorders. CNS spectrums. 2017;22(5):404-6.
2. Uher R, Payne JL, Pavlova B, Perlis RH. Major depressive disorder in
DSM‐5: Implications for clinical practice and research of changes from
DSM‐IV. Depression and anxiety. 2014;31(6):459-71.
3. Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M,
et al. Visceral Adiposity Index: a reliable indicator of visceral fat function
associated with cardiometabolic risk. Diabetes care. 2010;33(4):920-2.
4. Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox
CS. Body fat distribution, incident cardiovascular disease, cancer, and
all-cause mortality. Journal of the American College of Cardiology.
2013;62(10):921-5.
5. Biswas E, Choudhury A, Amin M, Khalequzzaman M, Chowdhury
S, Kabir F, et al. Visceral Adiposity Index Score is the Better Predictor
of Clinical and Coronary Angiographic Severity Assessment than
Other Adiposity Indices in Patients with Acute Coronary Syndrome.
Mymensingh medical journal: MMJ. 2019;28(2):382-8.
6. Wang J, Liu EY, Freudenreich O, Goff D, Henderson DC, Fan X.
Phenotypic characteristics in metabolically obese but normal weight
non-diabetic patients with schizophrenia. Schizophrenia research.
2010;124(1-3):49-53.
7. Fain JN. Release of inflammatory mediators by human adipose tissue
is enhanced in obesity and primarily by the nonfat cells: a review.
Mediators of inflammation. 2010;2010.
8. Kahl KG, Deuschle M, Stubbs B, Schweiger U. Visceral adipose tissue
in patients with severe mental illness. Hormone molecular biology and
clinical investigation. 2018;33(1).
9. Coín-Aragüez L, Pavón FJ, Contreras A, Gentile A-M, Lhamyani S, De
Diego-Otero Y, et al. Inflammatory gene expression in adipose tissue
according to diagnosis of anxiety and mood disorders in obese and non-
obese subjects. Scientific reports. 2018;8(1):1-10.
10. Konarzewska B, Stefańska E, Wendołowicz A, Cwalina U, Golonko A,
Małus A, et al. Visceral obesity in normal-weight patients suffering from
chronic schizophrenia. BMC psychiatry. 2014;14(1):35.
 Sahin SK / Arch Clin Psychiatry. 2021;48(1): 01-05
11. Cho SJ, Lee HJ, Rhee SJ, Kim EY, Kim K-N, Yoon DH, et al. The
relationship between visceral adiposity and depressive symptoms in the
general Korean population. Journal of affective disorders. 2019;244:54-9.
12. Murabito JM, Massaro JM, Clifford B, Hoffmann U, Fox CS. Depressive
symptoms are associated with visceral adiposity in a community‐based
sample of middle‐aged women and men. Obesity. 2013;21(8):1713-9.
13. Hillman JB, Dorn LD, Huang B. Association of anxiety and depressive
symptoms and adiposity among adolescent females, using dual energy
X-ray absorptiometry. Clinical pediatrics. 2010;49(7):671-7.
14. Alshehri T, Boone S, de Mutsert R, Penninx B, Rosendaal F, le Cessie
S, et al. The association between overall and abdominal adiposity
and depressive mood: A cross-sectional analysis in 6459 participants.
Psychoneuroendocrinology. 2019;110:104429.
15. Amiri S, Behnezhad S. Obesity and anxiety symptoms: A systematic
review and meta-analysis. neuropsychiatrie. 2019;33(2):72-89.
16. Jantaratnotai N, Mosikanon K, Lee Y, McIntyre RS. The interface
of depression and obesity. Obesity research & clinical practice.
2017;11(1):1-10.
17. Papakostas GI, Petersen T, Iosifescu DV, Burns AM, Nierenberg AA,
Alpert JE, et al. Obesity among outpatients with major depressive
disorder. International Journal of Neuropsychopharmacology.
2005;8(1):59-63.
18. Patterson B, Van Ameringen M. Augmentation Strategies for Treatment-
Resistant Anxiety Disorders: A Systematic Review and Meta-Analysis.
Focus. 2017;15(2):219-26.
19. Hamilton M. A rating scale for depression. Journal of neurology,
neurosurgery, and psychiatry. 1960;23(1):56.
5
20. Akdemir A, Örsel S, Dağ İ, Türkçapar H, İşcan N, Özbay H. Hamilton
Depresyon Derecelendirme Ölçeği (HDDÖ)’nin geçerliği, güvenirliği
ve klinikte kullanımı. Psikiyatri Psikoloji Psikofarmakoloji Dergisi.
1996;4(4):251-9.
21. Hamilton M. The assessment of anxiety states by rating. British journal
of medical psychology. 1959;32(1):50-5.
22. Yazıcı M, Demir B, Tanrıverdi N, Karaağaoğlu E, Yolaç P. Hamilton
Anksiyete Değerlendirme Ölçeği, değerlendiriciler arası güvenirlik ve
geçerlik çalışması. Türk Psikiyatri Dergisi. 1998;9(2):114-7.
23. Everson-Rose SA, Lewis TT, Karavolos K, Dugan SA, Wesley D, Powell
LH. Depressive symptoms and increased visceral fat in middle-aged
women. Psychosomatic medicine. 2009;71(4):410.
24. Coryell WH, Butcher BD, Burns TL, Dindo LN, Schlechte JA, Calarge
CA. Fat distribution and major depressive disorder in late adolescence.
The Journal of clinical psychiatry. 2016;77(1):84.
25. Milaneschi Y, Simmons WK, van Rossum EF, Penninx BW. Depression
and obesity: evidence of shared biological mechanisms. Molecular
psychiatry. 2019;24(1):18-33.
26. Sahin SK, Elboga G, Kilic OHT, Sahin AZ, Unal A, Altindag A. Metabolic
syndrome in patients with schizoaffective disorder and relationship with
the antipsychotics. Acta medica mediterranea. 2018;34(1):133-7.
27. Hawkins MA, Stewart JC. Do negative emotional factors have
independent associations with excess adiposity? Journal of
psychosomatic research. 2012;73(4):243-50.
28. Aparicio E, Canals J, Voltas N, Hernández-Martínez C, Arija V.
Emotional psychopathology and increased adiposity: Follow-up study
in adolescents. Journal of adolescence. 2013;36(2):319-30.
 Original article

The relationship between childhood traumas and stressors of recent year with suicide
attempt and general health in adulthood
Hourivash Ghaderi1*
https://orcid.org/0000-0002-1177-1922
Mohsen Khosravi2*
https://orcid.org/0000-0001-5937-6035
Ali Hasanpour Dehkordi3
https://orcid.org/0000-0003-4285-8497

1Assistant Professor, Department of Psychiatry, Shahrekord University of Medical Sciences, Shahrekord, Iran
2General Practitioner, Shahrekord University of Medical Sciences, Shahrekord, Iran
3Associated Professor, Social Determinants of Health Research Center, School of Allied Medical Sciences, Shahrekord University of Medical Sciences, Shahrekord, Iran

*Both authors contributed equally to this work.

Received: 01-01-2019 – Accepted: 31-08-2020

DOI: 10.1590/0101-60830000000270

ABSTRACT
Background and Objective: Suicide is a major health problem in adult, and it is estimated that by 2020 every 20 seconds, a death due to
suicide occurs on average every 20 seconds. Therefore, by comprehensive investigating of this social problem and finding ways to cope,
the deaths from suicide should be minimized. Since base of adulthood has been built in childhood, this study aimed to investigate the
relationship between childhood injuries and stressors of a recent year with suicidal attempts and general health in adulthood.
Materials and Methods: This is a case-control study. The sample of this study was 156 people referred and hospitalized to Kashani Hospital
in Shahrekord city. The samples were randomly divided into two groups: control (78) and case (experiment) (78). Data were collected
by Childhood Trauma questionnaire (CTQ: physical neglect, emotional neglect, sexual abuse, physical abuse, emotional abuse), General
Health Questionnaire (GHQ), Holmes and Rahe Stress Scale Questionnaire and were analyzed using SPSS 20 software. In this study, Chi-
square, T test, Mann-Whitney, Scheffe and variance analysis were used.
Results: GHQ scores in case and control groups were 45.47 and 35.34 respectively. In CTQ items results show that only emotional neglect
has higher score in case group (16.33 versus 14.32 in control group). Scores of Holms and Rahe Questionnaire were 180.20 and 173.88 in
case and control groups respectively. According to these results there was a significant difference between general health (p=0.006) and
emotional neglect (p=0.012) in two groups. But there was no significant difference between two groups in terms of stressors (P =0.701).
Conclusion: According to the results of this study, general health and childhood traumas especially emotional neglect are effective on
attempt to suicide in adulthood.

Ghaderi H / Arch Clin Psychiatry. 2021;48(1):06-11

Keywords: suicide, stressors, psychological traumas, childhood injuries

Introduction
Suicide is among the top ten causes of death in different countries of
the world, and annually more than 1 million people per year suicide1.
The suicide rate in Iran, though lower than that of other countries,
but a survey conducted in the country shows that it has increased
by 6 times in the years 1986-1997, regardless of population growth
over recent years2. The number of people who commit suicide in
Iran is about 5,000 in a year, in addition to the number of people who
commit suicide in different parts of the country, but are not included
in the annual statistics. Since every person who commits suicide
is a member of a six-member Iranian household, at least 30,000
people in our country somehow deal with the problem of suicide
and its psychological and social consequences. Suicide prevention
has always been a health issue and has always been a concern of
the Ministry of Health. Therefor Plans are currently underway to
"Prevent Suicide by treatment of Depression “and” Develop an
Integrated Suicide Prevention Program" at PHC since 2007 with the
aim of planning to reduce suicide rate through national planning.
According to published statistics, the rate of suicide has increased
Address for correspondence: Hourivash Ghaderi, Assistant Professor, Department of Psychiatry, Shahrekord University of Medical Sciences, Shahrekord, Iran, E-mail:ghaderi.
houri@gmail.com
from 1.3 in 100,000 in 1986 to 6.4 in 2005. Suicide was the ninth
leading cause of death in men with 7.6 per 100,000 populations
and tenth in mortality rate of 1.5 per 100,000. In recent years, due
to the increase in suicide attempt and other social problems that
have caused it, it has become necessary to pay more attention to
suicide prevention planning and to implement a suicide prevention
integration plan in the health network2. Investigations, had detected
that people with various chronic diseases such as diabetics, chronic
renal failure and cancer patients are more prone to suicide3-7.
Prevention of suicide has always been a health problem8. Although
the rate of suicide in Iran is very low compared to other advanced
(developed) industrial countries, studies from the past two decades
have shown that this problem is rising9. According to data from
53 countries in 1996, the standardized suicide rate according to
age was 15.1 per 100,000 people. This rate was reported 24 per
100000 in men and 6.8 per 100,000 in women10. Today, population
density in cities, heterogeneity of people together, feeling homesick,
loneliness, decreasing the number of families and decreasing
family affection, are among the factors of suicide attempt11. Many
suicidal behaviors, especially in adolescents, are related to social
7 Ghaderi H / Arch Clin Psychiatry. 2021;48(1): 06-11
factors, and these are more common in people whose family life has
been stressed for a long time12-15. According to the World Health
Organization (WHO), about 1 million people died due to suicide
in 2000, and it is estimated that 1,530,000 people would commit
suicide in 202016. Considering the increasing rate of suicide in the
world as well as in Iran, and considering the social, economic and
psychological consequences of suicide, the study of the underlying
causes of this problem seems necessary to prevent this global crisis.
Studies conducted in other countries attest to the relationship
between childhood traumatic and suicide attempts, but so far this
relationship has not been studied in Iran. Despite the fact that all
people with severe stressful experiences did not commit suicide,
however, all those who committed suicide had experienced stress17.
Research shows that children's disorders are closely linked to their
parents' psychological problems and their parental practices, and
spirituality affects suicide18. Several studies have also shown that
long-term emotional, physical, and sexual abuse of childhood
lead to cases such as personality disorders19-21. Substance abuse22,
major depression and suicide20-24. These conditions may be due
to previous anomalies or organ dysfunction that leads to major
depression and even suicide25-29. However, there is still no specific
mechanism for explaining the relationship between childhood
abuse and mental health problems in adulthood21,22,24. Studies on
substance abusers have shown that suicide history in the family, as
well as trauma in childhood and adolescence, have been correlated
with suicidal attempts in adulthood30,31. Severe traumas increase
impulsivity, which results in a reduction in brain capacity to inhibit
activities and control negative emotions. This impulsivity and
not inhibiting negative emotions increases self-harm behaviors
and suicide attempts23. The results of the studies show that in the
individuals who attempted suicide several times, the family history
of suicidal behavior and the rate of childhood and adolescence
abuse are higher32. Child abuse is a widespread international
problem and the consequences of it are different33. Emotional stress,
viral, malignancy, neural and endocrine organ malfunctions may
be the consequences of child abuse34-38. Child abuse is a general
term used to describe all forms of abuses: negligence, physical
abuse, sexual harassment, neglect and emotional harassment and,
more recently, domestic violence39. Child abuse affects children
of any race, color, social class, and religion, for all ages40. Of all 43
American children, one person is physically abused, particularly
in the first week of life, are neglected by parents. Approximately,
500 American children in each age group will be victimized
by unhealthy parenting behaviors41. The relationship between
childhood traumas and increased risk of suicidal behavior has been
seen in both general and clinical populations42. Childhood traumas
are significantly associated with early onset of suicide attempts32.
Unsafe attachment and childhood traumas are related to suicidal
behavior43. In a research on people with substance abuse, it was
found that the history of suicide in the family, as well as childhood
and adolescent trauma, led to the prevalence of suicidal behaviors
in adulthood24,30,31,41. Therefore, with the increasing rate of suicide
in the world as well as in Iran, and given that suicide because of
its social, economic and psychological consequences imposes
abundant losses to society, studying the underlying factors in this
regard in order to prevent the world crisis seems indispensable.
Therefore, factors that can predict suicide behavior are very
important. For this, the aim of this study was to determine the
relationship between childhood traumas and stressors of a recent
year with suicide attempt and general health in patients referred to
Kashani Hospital in Shahrekord, Iran.
Materials and methods
The present study is a case-control one. This project was approved
at the Ethics Committee of the Research and Technology Dept.
of Shahrekord University of Medical Sciences. 156 subjects (in
two groups of case and control) referred to Hospital by using
convenience sampling method participated in this study. The case
group included individuals who were hospitalized for attempted
to suicide, and the control group were patients who were admitted
for another reason in the general department of hospital. The
participants were matched in age and gender.
In this study, standard questionnaires were used for data
collection. They included demographic information, Childhood
Trauma questionnaire (CTQ), General Health Questionnaire
(GHQ), Holmes and Rahe Stress Scale. Childhood Traumatic
Inventory (CTQ) with Cronbach's alpha between 0.79 and 0.9444,45,
the mental health status questionnaire (GHQ) with Cronbach's
alpha 0.90 (46, 47) and Holmes and Rahe Stress Scale with
Cronbach's alpha of 0.7248. CTQ is a 28-item self-report measure
which inquires about five types of maltreatment: 1) emotional
abuse, 2) physical abuse, 3) sexual abuse, 4) emotional neglect, and
5) physical neglect. A five-point Likert score is used for scoring.
For the never option, the number zero is considered. For the rarely
option number 1, sometimes option number 2, often option number
3 and very often option number 4 is considered. For physical neglect
and emotional neglect subscales. Scoring is reversed.
CTQ subscale scores are noted in Table 144,45.
GHQ-28 (28 item) is a psychometric screening tool that screen
prevalent psychiatric disorders. This instrument covers four main
areas: somatic symptoms, anxiety and insomnia, social dysfunction
and severe depression and each domain have 7 questions.
In this scale using behavioral items with a 4-point scale
indicating the following frequencies of experience: “not at all”, “no
more than usual”, “rather more than usual” and “much more than
usual”. The scoring system applied in this instrument is the Likert
scale 0, 1, 2, 3. The minimum score for the 28 version is 0, and the
maximum is 84. Higher GHQ-28 scores indicate higher levels of
distress. Participants with total scores of 23 or below should be
classified as non-psychiatric, while participants with scores > 24
may be classified as psychiatric46,47.
Holmes and Rahe Stress Scale: Thomas Holmes and Richard
Rahe constructed a social readjustment rating scale after asking
hundreds of persons from varying backgrounds to rank the relative
degree of adjustment required by changing life events. Holmes
and Rahe listed 43 life events associated with varying amounts of
disruption and stress in average persons' lives and assigned each of
them a certain number of units.
Interpretation of unites is as following:
150 unit or less: a relatively low amount of life change and a
low susceptibility to stress-induced health breakdown
150 to 300 unit: 50% chance of health breakdown in the next
2 years
300 unit or more: 90% chance of health breakdown in the
next 2 years, according to the Holmes-Rahe statistical prediction
model48.
Inclusion criteria included age 18-65, lack of psychosis
and physical illness, mental retardation, non-use of drugs or
substances, and informed consent, and the exclusion criteria
were non-cooperation and patients' death. After completing
the questionnaires, the collected data were analyzed using SPSS
software version 20 using Chi-square, T test, Mann-Whitney,
Scheffe and variance analysis.
Results
The results showed that there was no significant difference between
the two groups in terms of sex, education, marital status and place
of residence (Table 2).
 Ghaderi H / Arch Clin Psychiatry. 2021;48(1): 06-11 8

The results of the study regarding the relationship rate of Discussion

childhood trauma in two groups of case and control indicated that
there was a significant difference in emotional negligence between
the two groups (P <0.05). However, there is no significant difference
between the two groups in terms of physical neglect, sexual abuse,
physical abuse and emotional abuse (Table 3).
The results also showed a significant difference between the two
groups regarding general health (P <0.05), so that the case group
had lower general health (Table 4).
The results of the study indicate that there is a significant
difference between the two groups of case and control in terms
of general health components. So, in the case group, physical
symptoms, anxiety, social function and depression were in a worse
situation (Table 5).
In table 6 we show that the comparison of the stressors in the
two case and control groups was not statistically significant, so that
the two groups experienced equal stressors during the past year.
According to Table 6, the components of general health among
the case and control groups are significant based on repeated
suicide (P <0.05).
The results of the study showed that there are significant differences
between childhood traumas in two groups. So that emotional
negligence is most important. The importance of childhood
traumas in suicidal ideation in adulthood in different countries has
been reviewed. Afifi et al. reported that exposure to physical abuse,
sexual abuse, or witnessed domestic violence during childhood
increased by 16 to 50 percent the thoughts and behaviors of
suicidal attempts49. Similarly, clinical studies report that childhood
trauma is associated with suicidal attempts in adolescents with
various psychiatric disorders20. The results of the study by Shams
Alizadeh and colleagues showed that suicidal thoughts and suicide
attempts are prevalent and factors such as previous history of
suicide, education level, field of study, and residence have a direct
and significant relationship with suicidal attempts2. The results of
this study showed that there is a significant relationship between
general health and spiritual health in the two groups. The results
of other studies showed that the general health of people and the
symptoms of depression were significantly associated with an

Tabe 1: subscale scores of CTQ

Severity of abuse Physical neglect Emotional neglect Sexual abuse Physical abuse Emotional abuse
None 7≤ 9≤ 5≤ 7≤ 8≤
Low 8 -9 21 -21 6 -7 8 -9 9 -21
Moderate 21 -21 21 -27 8 -21 21 -21 21 -21
Severe 13≥ 18≥ 13≥ 13≥ 16≥

Table 2: Demographic characteristics of case and control groups

Groups P value
Variable
Group Control Case (experiment)
Number Percent Number Percent
Male 30 38.5 31 7.39 0.87
Gender
Female 48 61.5 47 3.60 0.56
Illiterate 0 0 1 1.3
Elementary 9 11.5 11 14.1
Secondary 17 21.8 18 23.1
High School 30 38.5 26 33.3
Education 0.421
Associate degree 0 0 2 2.6
Bachelor 15 19.2 18 23.1
Master 5 6.4 2 2.6
Ph.d 2 2.6 0 0
Unmarried (single) 37 47.4 44 56.4
Married 30 38.5 20 25.6
Marital status 0.384
Divorced 5 6.4 8 10.3
Widow 6 7.7 6 7.7
Shahrkord 41 51.3 50 64.1
Location (Adress) 0.25
Non-Shahrkord 36 48.8 28 35.9

Table 3: Childhood traumas scores in case and control groups

Childhood traumas Mean± Standard deviation P-value
Control Case
physical neglect 17.47±5.08 18.5±5.46 0.425
emotional neglect 14.32±5.58 16.33±5.7 0.012*
sexual abuse 22.5±4.02 21.41±4.2 0.124
physical abuse 19.66±3.63 18.7±4.71 0.429
emotional abuse 16.35±4.99 17.74±5.8 0.066
*: Indicates a significant difference at the level of p <0.05
9 Ghaderi H / Arch Clin Psychiatry. 2021;48(1): 06-11

Table 4: General health scores in two groups

Group General Health P-value
(mean ± standard deviation)
Case (Experiment) 45.47 ± 22.42
<0.05
Control 35.34±21.07

Table 5: Comparison of general health components scores in case and control groups
General health components Groups mean ± standard deviation p-value
Control 1.2674±1.765
Physical Symptoms 0.00*
Case 1.522±1.08
Control 1.2673±0.779
Anxiety 0.001*
Case 1.60±1.04
Control 1.2839±0.776
Social Function 0.00*
Case 1.6850±1.05
Control 1.2344±0.78
Depression 0.006*
Case 1.6868±1.08
*: Indicates a significant difference at the level of p <0.05

Table 6: Scores of stressors in case and control groups

Group Mean SD p-value
Control 173.88 103.85
0.701
Case (experiment) 180.20 103.56

increase in suicidal thoughts50. General health status and stress
levels of students and university students are significantly related to
suicidal ideation51. The results of this study, like the results of other
studies, show well the relationship between general health and
spiritual well-being with suicide attempt. There are many studies
that report that about one in five people who commit suicide have
contacted psychiatric clinics a month before committing suicide2.
The results of the study by Wile et al showed that providing mental
health services can reduce the suicide rate in the population, and
studying this relationship can help prevent suicide in the future
and improve the mental and spiritual conditions of patients52.
According to Conwell et al., mental illness and spiritual anomalies
are one of the most important risk factors for suicide53.
The results of Joiner et al. showed that general health in people
committing suicide is much lower54. Regarding the fact that there
was no difference between the last year`s stressors in the two
groups. It can be concluded that high stressors in the presence
of good general and mental health have little role in committing
suicide, although the relationship between stressors and suicide
attempts has been noted in various studies, it has even been pointed
out that patients who are being treated in emergency department
for suicide attempt they mention at least one of the stressors in their
lives55,56.
Conclusion
Based on the results, it can be admitted that the role of various factors
such as emotional neglect in childhood and general health in the
attempt to suicide in different societies and individuals is different
and in order to create solutions to prevent this phenomenon in
the community, the role of all these factors must be carefully
examined and steps taken to reduce these factors. Considering the
importance of the role of the childhood, it seems to be necessary
to provide parents with the necessary education for child-rearing
and children's emotional education as well as paying attention to
the spiritual and physical well-being of people of different ages and
creating programs to improve the health status of people, it would
be possible to greatly reduce suicide and its complications. Since in
Iran traditional parenting is dominant in almost families it seems
that classic and academic parenting training should be integrated in
to the health and education systems.
Acknowledgment
We express our thanks to Research and Technology Deputy of the
Shahrekord University of Medical Sciences, Shahrekord, Iran
References
1. Cooper J, Kapur N, Webb R, Lawlor M, Guthrie E, Mackway-Jones K,
et al. Suicide after deliberate self-harm: a 4-year cohort study. American
Journal of Psychiatry. 2005;162(2):297-303.
2. Malakouti SK, Davoudi F, Khalid S, Asl MA, Khan MM, Alirezaei N,
et al. The Epidemiology of Suicide Behaviors among the Countries of
the Eastern Mediterranean Region of WHO: a Systematic Review. Acta
Medica Iranica. 2015;53(5):257-65.
3. Sarokhani D, Parvareh M, Dehkordi AH, Sayehmiri K, Moghimbeigi A.
Prevalence of depression among iranian elderly: systematic review and
meta-analysis. Iranian journal of psychiatry. 2018;13(1):55.
4. Assadi F. Psychological impact of chronic kidney disease among children
and adolescents: Not rare and not benign. Journal of nephropathology.
2013;2(1):1.
5. Huh Y, Kim SM, Lee JH, Nam GE. Associations between the type and
number of chronic diseases and suicidal thoughts among Korean adults.
Psychiatry Research. 2021;296:113694. ( HYPERLINK \l "2)
6. Vasconcelos S. Hopelessness, suicide ideation, and depression in chronic
kidney disease patients on hemodialysis or transplant recipients. CEP.
2015;4023:900
7. Jhee JH, Lee E, Cha M-U, Lee M, Kim H, Park S, et al. Prevalence of
depression and suicidal ideation increases proportionally with renal
function decline, beginning from early stages of chronic kidney disease.
Medicine. 2017;96(44).
8. Organization WH. The world health report 2002: reducing risks,
promoting healthy life: World Health Organization; 2002.
9. Veisani Y, Delpisheh A, Moradi G, Hassanzadeh J, Sayehmiri K.
Inequality in Addiction and Mental Disorders in 6818 Suicide Attempts:
Determine of positive contribution of determinants by Decomposition
Method. Iranian Journal of Public Health. 2017;46(6):796-803.
 Ghaderi H / Arch Clin Psychiatry. 2021;48(1): 06-11
10. Hawton K, Van Heeringen K. The international handbook of suicide and
attempted suicide: John Wiley & Sons; 2000.
11. Mofidi N, Ghazinour M, Salander-Renberg E, Richter J. Attitudes
towards suicide among Kurdish people in Iran. Social psychiatry and
psychiatric epidemiology. 2008;43(4):291-8.
12. Dehkordi AH, Safavi P, Parvin N, Mosayebi B. Effect of methadone
maintenance treatment of opioid-dependent fathers on the mental
health and perceived family functioning of their children in Iran.
Addiction is a treatable disease. 2016:9.
13. Jalali A, Dehkordi AH, Mahvar T, Moradi M, Dinmohammadi M.
Psychological needs of men under methadone maintenance treatment:
A mixed method study. Heroin addiction and related clinical problems.
2015;17(1):23-31.
14. Solati K, Hasanpour-Dehkordi A. Effectiveness of cognitive-behavioural
stress management on self-efficacy and risk of relapse into symptoms of
substance use disorders. Addiction is a treatable disease. 2017.
15. Solati K, Hasanpour-Dehkordi A. Study of Association of Substance Use
Disorders with Family Members’ Psychological Disorders. Journal of
clinical and diagnostic research: JCDR. 2017;11(6):VC12.
16. Xing X-Y, Tao F-B, Wan Y-H, Xing C, Qi X-Y, Hao J-H, et al. Family
factors associated with suicide attempts among Chinese adolescent
students: a national cross-sectional survey. Journal of Adolescent
Health. 2010;46(6):592-9.
17. Sawyer SM, Afifi RA, Bearinger LH, Blakemore S-J, Dick B, Ezeh
AC, et al. Adolescence: a foundation for future health. The Lancet.
2012;379(9826):1630-40.
18. Sadock BJ, Sadock VA. Kaplan and Sadock's synopsis of psychiatry:
Behavioral sciences/clinical psychiatry: Lippincott Williams & Wilkins;
2011.
19. Gratz KL, Latzman RD, Tull MT, Reynolds EK, Lejuez C. Exploring
the association between emotional abuse and childhood borderline
personality features: The moderating role of personality traits. Behavior
Therapy. 2011;42(3):493-508.
20. Milner JS, Thomsen CJ, Crouch JL, Rabenhorst MM, Martens PM,
Dyslin CW, et al. Do trauma symptoms mediate the relationship
between childhood physical abuse and adult child abuse risk? Child
Abuse & Neglect. 2010;34(5):332-44.
21. Powers AD, Thomas KM, Ressler KJ, Bradley B. The differential effects of
child abuse and posttraumatic stress disorder on schizotypal personality
disorder. Comprehensive psychiatry. 2011;52(4):438-45.
22. Oviedo-Joekes E, Marchand K, Guh D, Marsh DC, Brissette S, Krausz
M, et al. History of reported sexual or physical abuse among long-term
heroin users and their response to substitution treatment. Addictive
behaviors. 2011;36(1):55-60.
23. Wingenfeld K, Schaffrath C, Rullkoetter N, Mensebach C, Schlosser N,
Beblo T, et al. Associations of childhood trauma, trauma in adulthood
and previous-year stress with psychopathology in patients with major
depression and borderline personality disorder. Child Abuse & Neglect.
2011;35(8):647-54.
24. Braquehais MD, Oquendo MA, Baca-García E, Sher L. Is impulsivity a
link between childhood abuse and suicide? Comprehensive psychiatry.
2010;51(2):121-9.
25. Ezeonwu BU, Nwafor I, Nnodim I, Ayodeji A, Ajaegbu O, Maduemem
E, et al. Risk factors for chronic kidney disease in children attending
pediatric outpatient clinic in federal medical center Asaba. Journal of
Preventive Epidemiology. 2017;1(2).
26. Fallahzadeh M-H, Fallahzadeh M-A. On the occasion of world kidney
day 2016; renal disease in children. Acta Persica Pathophysiologica.
2016;1(1).
27. Pakniyat A, Yousefichaijan P. Evaluation and management of children
with acute kidney injury in emergency department. Journal of
Nephropharmacology. 2015;4(2):83.
28. Safaei-Asl A, Heydarzadeh A, Karimi A, Maleknejad S. NPJ. Journal of
Nephropharmacology. 2017;6(2).
29. Sebdani AM, Alamdary MP, Abdollahpour N. Depression among
patients undergoing hemodialysis; a narrative review. Journal of
Preventive Epidemiology. 2017;3(1).
30. Elias B, Mignone J, Hall M, Hong SP, Hart L, Sareen J. Trauma and
suicide behaviour histories among a Canadian indigenous population:
an empirical exploration of the potential role of Canada's residential
school system. Social science & medicine. 2012;74(10):1560-9.
10
31. Roy A. Combination of family history of suicidal behavior and childhood
trauma may represent correlate of increased suicide risk. Journal of
Affective Disorders. 2011;130(1):205-8.
32. Mandelli L, Carli V, Roy A, Serretti A, Sarchiapone M. The influence
of childhood trauma on the onset and repetition of suicidal behavior:
An investigation in a high risk sample of male prisoners. Journal of
psychiatric research. 2011;45(6):742-7.
33. Li N, Ahmed S, Zabin LS. Association between childhood sexual abuse
and adverse psychological outcomes among youth in Taipei. Journal of
Adolescent Health. 2012;50(3):S45-S51.
34. Afsar Kazeroni P, Khazaei Z, Mousavi M, Sohrabivafa M, Adineh H,
Vali Esfahani M, et al. .The prevalence of HIV positivity among female
head of household in Shiraz Immunopathol Persa. 2017;3(2):e14.
35. Amiri M. Diabetes mellitus type 2; an international challenge. Annals of
Research in Dialysis. 2016;1(1).
36. Beladi-Mousavi SS, Bashardoust B, Nasri H, Ahmadi A, Tolou-Ghamari
Z, Hajian S, et al. The theme of the world diabetes day 2014; healthy living
and diabetes; a nephrology viewpoint. Journal of Nephropharmacology.
2014;3(2):43.
37. Kazeroni PA, Khazaei Z, Mousavi M, Khazaei S, Sohrabivafa M,
Dehghani SL, et al. Prevalence of human immunodeficiency virus and
tuberculosis among homeless individuals. Immunopathologia Persa.
2017;4(1).
38. Shahreza FD. From oxidative stress to endothelial cell dysfunction.
Journal of Preventive Epidemiology. 2016;1(1).
39. Bücker J, Kapczinski F, Post R, Ceresér KM, Szobot C, Yatham LN, et
al. Cognitive impairment in school-aged children with early trauma.
Comprehensive Psychiatry. 2012;53(6):758-64.
40. Branco BC, Inaba K, Barmparas G, Talving P, David J-S, Plurad D, et
al. Sex-related differences in childhood and adolescent self-inflicted
injuries: a National Trauma Databank review. Journal of pediatric
surgery. 2010;45(4):796-800.
41. Griffin ML, Amodeo M. Predicting long-term outcomes for women
physically abused in childhood: Contribution of abuse severity versus
family environment. Child abuse & neglect. 2010;34(10):724-33.
42. Brodsky BS, Mann JJ, Stanley B, Tin A, Oquendo M, Birmaher B, et
al. Familial transmission of suicidal behavior: factors mediating the
relationship between childhood abuse and offspring suicide attempts.
The Journal of clinical psychiatry. 2008;69(4):584.
43. Grunebaum MF, Galfalvy HC, Mortenson LY, Burke AK, Oquendo MA,
Mann JJ. Attachment and social adjustment: relationships to suicide
attempt and major depressive episode in a prospective study. Journal of
affective disorders. 2010;123(1):123-30.
44. Garrusi B, Nakhaee N. Validity and reliability of a Persian version
of the Childhood Trauma Questionnaire. Psychological reports.
2009;104(2):509-16.
45. O’Connor DB, Green JA, Ferguson E, O’Carroll RE, O’Connor RC.
Effects of childhood trauma on cortisol levels in suicide attempters and
ideators. Psychoneuroendocrinology. 2017.
46. Goldberg DP, Hillier VF. A scaled version of the General Health
Questionnaire. Psychological medicine. 1979;9(1):139-45.
47. Noorbala A, Mohammad K. The validation of general health
questionnaire-28 as a psychiatric screening tool. Hakim Research
Journal. 2009;11(4):47-53.
48. Heydari A, Namjoo Z. Comparison of alexithymia, attachment styles
and stress in men and women employees in Ahvaz. 2011.
49. Afifi TO, Boman J, Fleisher W, Sareen J. The relationship between child
abuse, parental divorce, and lifetime mental disorders and suicidality
in a nationally representative adult sample. Child abuse & neglect.
2009;33(3):139-47.
50. Poursharifi H, Habibi M, Zarani F, Ashouri A, Hefazi M, Hajebi A, et
al. The Role of Depression, Stress, Happiness and Social Support in
dentifying Suicidal Thoughts in Students. Iranian Journal of Psychiatry
and Clinical Psychology. 2012;18(2):99-107.
51. Zeinalzadeh AH, Viitasara E, Bahadori F, Sadeghi-Bazarghani H, Soares
J, Mohammadi R, et al. Suicidal ideation and its correlates among
high school students in Iran: a cross-sectional study. BMC psychiatry.
2017;17(1):147.
11 Ghaderi H / Arch Clin Psychiatry. 2021;48(1): 06-11
52. While D, Bickley H, Roscoe A, Windfuhr K, Rahman S, Shaw J, et al.
Implementation of mental health service recommendations in England
and Wales and suicide rates, 1997–2006: a cross-sectional and before-
and-after observational study. The Lancet. 2012;379(9820):1005-12.
53. Conwell Y, Duberstein PR, Caine ED. Risk factors for suicide in later life.
Biological psychiatry. 2002;52(3):193-204.
54. Joiner TE, Pfaff JJ, Acres JG. A brief screening tool for suicidal symptoms
in adolescents and young adults in general health settings: reliability and
validity data from the Australian National General Practice Youth Suicide
Prevention Project. Behaviour research and therapy. 2002;40(4):471-81.
55. Bolton JM, Cox BJ, Afifi TO, Enns MW, Bienvenu OJ, Sareen J. Anxiety
disorders and risk for suicide attempts: findings from the Baltimore
Epidemiologic Catchment area follow‐up study. Depression and
Anxiety. 2008;25(6):477-81.
56. Yoshimasu K, Kiyohara C, Miyashita K, Hygiene SRGotJSf. Suicidal risk
factors and completed suicide: meta-analyses based on psychological
autopsy studies. Environmental health and preventive medicine.
2008;13(5):243-56.
 Original article

Brief Symptom Inventory: reporting Brazilian populational parameters during COVID-19

pandemics
Alexandre Luiz de Oliveira Serpa1
https://orcid.org/0000-0002-1924-2128

Debora Marques de Miranda2

Danielle de Souza Costa3
Jonas Jardim de Paula4,5
https://orcid.org/0000-0001-5530-2346

Mayra Isabel C. Pinheiro6

Alexandre Paim Diaz7
https://orcid.org/0000-0002-6591-6648

Antônio Geraldo Silva8

Leandro Fernandes Malloy-Diniz9,10
1Social and Cognitive Neuroscience Lab, Mackenzie Presbyterian University, Sao Paulo, Brazil.
2Pediatrics Department, Neuroscience Lab, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
3Neuroscience Lab, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
4Neuroscience Lab, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

5Department of Psychology, Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, MG, Brazil

6Ministério da Saúde – SGETS, Belo Horizonte, MG, Brazil

7Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.

8Brazilian Psychiatry Association, Porto University, Brazil

9Mental Health Department, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

10Universidade FUMEC, Belo Horizonte, Brazil

Received: 21/08/2020– Accepted: 03-09-2020

DOI: 10.1590/0101-60830000000271

Abstract
Background: The Brief Symptoms Inventory is a valid and reliable instrument, and one of the most often used tools to assess mental health.
Despite its translation to Brazilian Portuguese, there are no normative parameters for interpretation of its scores. Objective: This study
provides a normative parameter for interpretation of the performance of a large sample of adults by using a version of BSI adapted to Brazilian
Portuguese. Method: We assessed 2127 adults (57% female) from all of the Brazilian regions. Normative data and Internal consistencies
and performance data were calculated for the general score index and the nine factors. Results: The associations between gender and BSI
scores present a significant effect size. Therefore, we provided a percentile rank parameter for the different BSI subscores, considering the
whole sample and gender division. Internal consistency varies from omega equal .87 – .98 and alpha equal .86-.98, which suggests that both
GSI and the nine factors have excellent reliability. Discussion: Our results support the use of the Brazilian adaptation of BSI in different
regions of the country to measure mental health and its specific factors. During the pandemic of COVID-19, the establishment of normative
parameters is of utmost relevance. The stability of the parameters reported here should be addressed in future studies.

de Oliveira Serpa AL / Arch Clin Psychiatry. 2021;48(1):12-15

Keywords: psychological assessment, psychiatric assessment, normative data, psychometrics, mental health

Introduction The Brief Symptoms Inventory4 is a screening tool used in

mental health practices to assess symptoms of depression, anxiety,
Mental Health is an essential target in clinical practices during
somatization, obsession-compulsion, interpersonal sensitivity,
COVID-19 pandemics1. The outburst of psychiatric symptoms was
phobic anxiety, hostility paranoid ideation, and psychoticism.
reported since the beginning of the pandemics. For example, Wang
Moreover, BSI reports a Global Severity Index (GSI) composed
et al.2 reported the immediate impact of pandemics on Chinese
of all symptoms assessed by the scale. The scale presents some
subjects' mental health, with the increased symptoms of internalizing
alternative versions composed of specific items, and in some studies,
symptoms and stress perception. Similar data were reported in a
its specific subscales are used to assess some of the mental health
Germany sample suggesting that symptoms of generalized anxiety
constructs. For example, during COVID-19 pandemics Wang et
and major depression increased during pandemics3. The impact of
al.,5 used the BSI hostility scale to assess mental health in cancer
pandemics in lifestyle promotes changes in how people deal with
patients. In another study, Ellis et al.,6 used BSI depression items to
work, education, social relationships, nutrition, physical activities, assess depressive symptoms in adolescents and its relationship with
and general health. The impact of life change and fear of disease the distress induced by social distancing measures adopted during
reinforces the need to monitor population mental health during pandemics.
this period.
Address for correspondence: Alexandre Luiz de Oliveira Serpa, Social and Cognitive Neuroscience Lab, Mackenzie Presbyterian University, Sao Paulo, Brazil.
13 de Oliveira Serpa AL / Arch Clin Psychiatry. 2021;48(1): 12-15
During Covid-19 pandemics, mental health assessment scales
have been used to assess many people. This strategy provides an
economical and efficient resource in monitoring mental health
throughout time and providing an opportunity for mental health
guidelines to professionals, policymakers, and general population6-7.
For example, Tian et al., 7 using the SLC-90 scale (which measures
the same constructs assessed by BSI) during pandemics, found an
increase of obsessive-compulsive symptoms, phobic anxiety, and
psychoticism. In this paper, authors provide specific suggestions
derived from the scales results, considering age, educational level,
and specificities concerning risk groups.
BSI was translated to Portuguese, but there is no normative data
to interpretation of its scores considering Brazilian populational
parameters. This lack of norms hinder its potential to use by
clinicians and policymakers to use the scale for screening and
monitoring population mental health throughout COVID-19
pandemic. This study provides BSI normative data for the adult
Brazilian population.
Methods
An online questionnaire was used, and the data was collected
from May to June 2020. Participants were recruited by online
advertisements in social media of the Brazilian Association of
Psychiatry, Brazilian Association of Dual Pathology and by the
Universidade Federal de Minas Gerais. We included only those
participants from 20-80 years old. The questionnaire was delivered
by the SurveyMonkey platform. The participants agreed with the
informed consent before starting to answer the questionnaire.
The procedures have been approved by the National Commission
on Ethics in Research under the process number CAAE:
30823620.6.0000.5149.
Participants
The participants are 6130 Brazilian adults, with a mean of 42.2 (SD
= 13.2, Min = 20, Max = 90) years old, from all Brazilian regions.
From that, 82% are female, and around 50% had a university degree
and are married or have a stable relationship. In terms of social
class, 71% are in class B2 or superior, according to the Brazilian
Economic Classification Criteria (BECC), and 55% reported never
having been diagnosed with a mental disorder. This initial sample
was submitted to a resampling procedure considering several
criteria. The procedure is detailed in the “data preparation” session
below.
Brief Symptoms Inventory (BSI)
The Brief Symptom Inventory (BSI) is a 53-item instrument
designed to identify relevant psychological symptoms. The BSI is
suitable for adolescents until 13 years old, adults and older adults, for
both clinical and non-clinical groups. The questionnaire provides
scores in nine dimensions, covering several psychiatric symptoms
of Somatization, Obsession-Compulsion, Interpersonal Sensitivity,
Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid Ideation,
and Psychoticism conditions. It is also possible to calculate three
general indexes, the Global Severity Index (GSI), Positive Symptom
Distress Index (PSDI), and Positive Symptom Total (PST). The items
were answered on a 5-points Likert scale from 0 (not at all) to 4
(extremely), and the alpha reliability ranges from .71 (Psychoticism)
to .85 (Depression) according to the original manual. In addition,
test-retest reliability was provided by global indices, ranging from
.87 (PSDI) to .90 (GSI) and for all dimensions that range from .68
(Somatization) to .91 (Phobic Anxiety).
The nine dimensions plus the GSI index were replicated in a
Brazilian sample8, indicating a bifactor structure for the BSI. For
that sample, the omega reliability was slightly better, ranging from
.83 (Paranoid Ideation) to .94 (Anxiety) for the factors and .98 to
GSI.
Procedure
Participants were recruited from the internet by a social media
campaign between May and July/2020. The participants had access
to the questionnaires by the SurveyMonkey platform and should
agree with the informed consent. After that step, they proceed to
the tests and questionnaires. This research was approved by the
National Commission on Ethics in Research under the process
number CAAE: 30823620.6.0000.5149 following the Declaration of
Helsinki.
Data preparation
To ensure that the norms meaning should be generalized for the
population is necessary to create a norm-referenced group that have
a similar variability on the interest variable than the population9. In
that study, three variables have been taken into consideration, and
the reference representatives were based on populational reports
from the Brazilian Institute of Geography and Statistics (IBGE).
Then, it is expected for the norm-reference sample the foresee
characteristics: sex (50.83% female), geographic region (7.8%
North, 26.2% Northeast, 43.4% Southeast, 14.8% South and 7.7%
Middle-West) and the presence or absence of self-reported previous
mental disorder diagnosis (80% absence). To determine the sample
size, we proceed a sample size calculation with an interval of 95%
confidence and a sample error of 2%, which resulted in an estimated
n of 2401. A random selection was made from the primary dataset,
to create the norm-referenced dataset.
Statistical procedures
After the data preparation, the norm-referenced data was exported
to Jamovi10, and the scores were calculated for each of the nine
dimensions and for the Global Severity Index. The score was
based on the original procedure, with calculates the mean of the
answered items that composed each factor or the GSI. The missing
items are not used. Five percentiles of interest were calculated,
the 5th, 25th, 50th, 75th, and 95th percentile. Due to differences
reported for males and females, the norms are also calculated for
each group. Finally, internal consistency (omega and alpha) was
calculated for GSI and each of the nine factors from the bifactor
model with semTools11 and BifactorIndicesCalculator12 packages
from R software13.
Results
After the resampling procedure, our final sample was composed
of 2127 participants (57% female), mainly with a university degree
level of education (49%), residing in the southeast region (48.7%),
and married or living a stable relationship (55%). The age ranges
from 20 throughout 82 years (42.4 ± 13.6 years old). Considering
the presence of a diagnostic of mental health disorder in that
sample, 21.8% of the participants self-reported having at least one
mental health disorder formally diagnosed, and 75% were on B2 or
superior class according to BECC.
The norms are presented in Table 1. In general, the reference
scores for females are systematically higher than those for males.
Considering the 50th percentile, the dimension with higher
reference scores are Obsession-Compulsion, Depression, and
Anxiety for the general population; Obsession-Compulsion and
Anxiety for females; and Obsession-Compulsion, Depression,
and Anxiety for males. For all groups, the lower scores at the
50th percentile were on the Somatization dimension. Internal
consistency varies from omega equal 0.87 – 0.98 and alpha equal
 de Oliveira Serpa AL / Arch Clin Psychiatry. 2021;48(1): 12-15 14

Table 1. Reliability and norming references from a Brazilian sample for BSI.
BSI GSI Somatization Obs-Com Int-Sens Depression
Reliability (omega; alpha) .99; .98 .90; .90 .93; .92 .92; .91 .93; .93
5th percentile General 0,08 0,00 0,00 0,00 0,00
Female 0,09 0,00 0,00 0,00 0,00
Male 0,06 0,00 0,00 0,00 0,00
25th percentile General 0,32 0,00 0,33 0,00 0,33
Female 0,38 0,14 0,50 0,00 0,33
Male 0,26 0,00 0,33 0,00 0,33
50th percentile General 0,67 0,29 0,83 0,50 0,83
Female 0,76 0,43 1,00 0,50 0,83
Male 0,57 0,14 0,67 0,50 0,67
75th percentile General 1,25 0,86 1,67 1,25 1,50
Female 1,36 1,00 1,83 1,25 1,67
Male 1,08 0,57 1,50 1,25 1,33
95th percentile General 2,36 2,00 2,83 3,00 3,17
Female 2,45 2,14 3,00 3,00 3,17
Male 2,18 1,71 2,83 2,75 3,15
BSI Anxiety Hostility Phobic Anxiety Paranoid Psychoticism
Reliability (omega; alpha) .95; .94 .93; .91 .90; .87 .87; .87 .89; .86
5th percentile General 0,00 0,00 0,00 0,00 0,00
Female 0,00 0,00 0,00 0,00 0,00
Male 0,00 0,00 0,00 0,00 0,00
25th percentile General 0,33 0,20 0,20 0,20 0,00
Female 0,50 0,20 0,20 0,20 0,20
Male 0,17 0,20 0,00 0,20 0,00
50th percentile General 0,83 0,60 0,80 0,60 0,40
Female 1,00 0,60 0,80 0,60 0,40
Male 0,67 0,60 0,60 0,60 0,40
75th percentile General 1,50 1,20 1,60 1,20 1,00
Female 1,67 1,20 1,80 1,20 1,20
Male 1,17 1,20 1,20 1,20 1,00
95th percentile General 2,83 2,60 2,80 2,40 2,31
Female 3,00 2,60 3,00 2,40 2,40
Male 2,67 2,40 2,80 2,40 2,20

0.86-0.98, which suggests that both GSI and the nine factors have
excellent reliability.
Discussion
The present data is the first report of Brief Symptoms Inventory
parameters scores in a large Brazilian sample from all regions. We
reported here populational parameters considering mental health
symptoms during the early months of COVID-19 pandemics.
The parameters obtained in this study are different from those
suggested in the original BSI manual adopted in Brazil. Both in
GSI and the specific scales, we found higher scores in our sample
than those reported in Brazilian Manual. Furthermore, comparing
our datacom previously reported by Trucato et al.,14, and we found
the same increasing of mental health symptoms in our sample.
Nonetheless, the results reported in this case-control study are
more like the reported in the present studies compared to those
reported in the BSI manual. Differences between Brazilian and
American samples were reported in other mental health screening
tools15. This could be related to the effect of pandemics due to its
effects on everyday life since, as reported by other recent studies,
there is an increase in mental health symptoms during COVID-19
pandemics. Future studies should address the stability of this
pattern throughout time, assessing if this score represents new
normality.
The reliability is good for the Brazilian sample, been slightly
better for the norm-referenced sample then the magnitudes found
in the first Brazilian study8. The omega reliability found in this
study is like those reported for the Hungarian16-17 and Dutch17
populations, and the alpha reliability is higher than those reported
for Italian18 and Azerbaijani19 populations. The cross-cultural
evidence about the reliability of BSI may indicate that the scale
15 de Oliveira Serpa AL / Arch Clin Psychiatry. 2021;48(1): 12-15
could be a valuable tool for international comparisons on mental
health conditions. However, studies addressing evidence of validity
for the meaningful interpretation of the scores considering different
contexts and groups, like clinical and non-clinical samples, must be
developed to support this intent.
Our results present limitations that should be considered. First, we
did not have previous BSI parameters to verify it there is an increase
of symptoms presentation during this period. The parameter
reported here can be considered because of populational distress
during pandemics or even a cultural difference considering the
original sample. Nonetheless, the increase of symptoms during this
period can require new interpretation parameters since the increase
of symptoms does not necessarily represent a disorder, but a mental
health load related to new challenges and adaptation. Besides,
despite the efforts to adequately represent all the Brazilian regions,
some bias remains, especially regarding male participants in the
Northeast region. The socioeconomic class was not also eligible as
a criterion for the norm-sample reference. Most of the participants
came from the superior socioeconomic strata and will not be able
to have a suitable representation of the overall population for that
characteristic. It should be addressed for future works.
The use of scales assessing mental health symptoms related to
traumatic events is important to monitoring people considering
clinical, research and public policy targets 20. Nonetheless, we
have a new question to address in future researches. Since this
pandemic and its consequences have a probably long duration, new
parameters to old screening tasks should be necessary for clinical
and public policy decisions.
Acknowledgements
This work was supported PAHO - Panamerican Health
Organization [grant number SCON2020-00202] and CNPQ [grant
number 401542/2020-3] in task force with Brazilian Association of
Psychiatry (ABP), Brazilian Association of Impulsivity and Dual
Patology (ABIPD ) and SAMBE Research Group.
The authors address special acknowledgment for Instituto Genus
and Pearson for supporting the study and permission to use BSI.
References
1. da Silva AG, Miranda DM, Diaz AP, Teles ALS, Malloy-Diniz LF, Palha
AP. Mental health: why it still matters in the midst of a pandemic. Braz J
Psychiatry. 2020;42(3):229-231. doi:10.1590/1516-4446-2020-0009
2. Wang C, Pan R, Wan X, Tan Y, Xu L, Ho CS, et al. Immediate
psychological responses and associated factors during the initial stage of
the 2019 coronavirus disease (COVID-19) epidemic among the general
population in china. Int J Environ Res Public Health. 2020;17:1729
3. Bäuerle A, Teufel M, Musche V, Weismüller B, Kohler H, Hetkamp M,
et al. Increased generalized anxiety, depression and distress during the
COVID-19 pandemic: a cross-sectional study in Germany. Journal of
Public Health. 2020;42(4): 672–678.
4. Derogatis LR, Savitz KL. The SCL-90-R and Brief Symptom Inventory
(BSI) in primary care. In Handbook of Psychological Assessment in
Primary Care Settings; Maruish ME., Ed.; Lawrence Erlbaum Associates:
Mahwah, NJ, USA, 2000; pp. 297–334.
5. Wang Y, Duan Z, Ma Z, et al. Epidemiology of mental health problems
among patients with cancer during COVID-19 pandemic. Transl
Psychiatry. 2020;10(1):263.
6. Ellis WE, Dumas TM, Forbes LM. Physically isolated but socially
connected: Psychological adjustment and stress among adolescents during
the initial COVID-19 crisis. Canadian Journal of Behavioural Science /
Revue canadienne des sciences du comportement. 2020;52(3):177-187.
7. Tian F, Li H, Tian S, Yang J, Shao J, Tian C. Psychological symptoms of
ordinary Chinese citizens based on SCL-90 during the level I emergency
response to COVID-19. Psychiatry Res. 2020;288:112992.
8. Malloy-Diniz L, de Oliveira Serpa AL, de Souza Costa D, Pinheiro MIC,
Diaz AP, de Paula JJ, et al. Brief Symptoms Inventory psychometric
properties supports the hypothesis of a general psychopathological
factor. https://doi.org/10.31234/osf.io/7jk2r
9. Reynolds CR, Livingston RB. The meaning of test scores. In C. R.
Reynolds & R. B. Livingston. Mastering Modern Psychological Testing:
Theory & Methods. London: Pearson. 2014. Pp: 75-114.
10. The jamovi project (2020). jamovi (Version 1.2) [Computer Software].
Retrieved from https://www.jamovi.org
11. Jorgensen TD, Pornprasertmanit S, Schoemann AM, Rosseel Y. semTools:
Useful tools for structural equation modeling. R package version 0.5-3.
2020. Retrieved from https://CRAN.R-project.org/package=semTools
12. David Dueber (2020). BifactorIndicesCalculator: Bifactor Indices
Calculator. R package version 0.2.1. https://CRAN.R-project.org/package
=BifactorIndicesCalculator
13. R Core Team (2020). R: A language and environment for statistical
computing. R Foundation for Statistical Computing, Vienna, Austria.
URL https://www.R-project.org/.
14. Turcato TD, Carolina PL, Fernanda BS Obesidade, características de
personalidade e sofrimento psicológico: um estudo de caso controle.
Quaderns de Psicologia. 2017;19(1):59-71.
15. Rescorla LA, Blumenfeld MC, Ivanova MY, Achenbach TM, International
Aseba Consortium. International Comparisons of the Dysregulation
Profile Based on Reports by Parents, Adolescents, and Teachers. J Clin
Child Adolesc Psychol. 2019;48(6):866-880.
16. Urbán R, Kun B, Farkas J, Paksi B, Kökönyei G, Unoka Z, et al. Bifactor
structural model of symptom checklists: SCL-90-R and Brief Symptom
Inventory (BSI) in a non-clinical community sample. Psychiatry
Research. 2014;216(1):146–154.
17. Urbán R, Arrindell WA, Demetrovics Z, Unoka Z, Timman R. Cross-
cultural confirmation of bi-factor models of a symptom distress
measure: Symptom Checklist-90-Revised in clinical samples. Psychiatry
Research. 2016;239:265–274.
18. Adawi M, Zerbetto R, Re TS, Bisharat B, Mahamid M, Amital H, et al.
Psychometric properties of the brief symptom inventory in nomophobic
subjects: Insights from preliminary confirmatory factor, exploratory
factor, and clustering analyses in a sample of healthy italian volunteers.
Psychology Research and Behavior Management. 2019;12:145–154.
19. Kerimova M, Osmanli N The Brief Symptom Inventory: A validity-
reliability Study of a Sample from Azerbaijan. Journal of Education and
Training Studies. 2016;4(12):153–159.
20. Magalhãeas SdS, Miranda DK, de Paula JJ, de Miranda DM, Romano-
Silva MA, Malloy-Diniz LF. Psychometric properties of a Brazilian
Portuguese version of the Children's Revised Impact of Event Scale
(CRIES-8). Arch. Clin. Psychiatry (São Paulo). 2018, 45(2):27-32.
 Original article

Increased serum nesfatin-1 levels among adolescents diagnosed with major depressive
disorder
S. Burak Acikel1
https://orcid.org/0000-0002-8964-9513
Esra Hosoglu2
https://orcid.org/0000-0003-0090-1389
Abdulbaki Artik3
https://orcid.org/0000-0001-7909-9944
Fatma Humeyra Yerlikaya Aydemir4
https://orcid.org/0000-0002-4107-5389

1Department of Child and Adolescent Psychiatry, Konya City Hospital, Konya, Turkey
2Department of Child and Adolescent Psychiatry, Giresun University, School of Medicine, Giresun Turkey
3Department of Child and Adolescent Psychiatry, Kayseri City Hospital, Kayseri Turkey
4Department of Biochemistry, School of Medicine, Selcuk University, Konya, Turkey

Received: 11-06-2020– Accepted: 10-09-2020

DOI: 10.1590/0101-60830000000272

ABSTRACT
Background: Nesfatin-1 is an anorexigenic protein expressed in the hypothalamus. Besides the effect on appetite, nesfatin-1 has some
effect on mood. In this study, we aimed to investigate the relationship between serum nesfatin-1 levels and major depressive disorder in
adolescents diagnosed as major depressive disorder.
Methods: A total of 30 patients between the ages of 12 and 18 with primary diagnosis of major depressive disorder have been included.
Depressive scores of both groups were measured by the Children’s Depression Inventory. Serum nesfatin-1 concentrations were measured
by a commercially available kit based on the enzyme-linked immunosorbent assay (ELISA) method.
Results: The mean serum nesfatin-1 levels in patients with MDD was 40.11±1.62 pg/ml, whereas it was 37.51±5.10 pg/ml in healthy controls.
Mean serum nesfatin-1 levels difference between groups was statistically significant. There is a positive correlation between serum nesfatin-1
levels and CDI scores in the whole sample.
Discussion: This is the first study to examine the relationship between major depressive disorder and serum nesfatin-1 levels in adolescents
diagnosed as major depressive disorder. Further studies are needed to clarify this relationship.

Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1):16-19

Keywords: depression; adolescent; nesfatin-1; depressive disorder

Introduction
Nesfatin-1 is an anorexigenic protein expressed in the hypothalamus
which was discovered in 2006. Its name is an abbreviation of NEFA/
nucleobindin 2 encoded satiety-and fat-influencing protein1.
Nesfatin-1 was previously discovered in the hypothalamus, which
is in the central nervous system, but it also exists in peripheral
tissue. Specifically, it is secreted by peripheral adipose tissue, gastric
mucosa, pancreatic endocrine beta cells, and testis tissue2. In terms
of appetite, nesfatin-1 has an anorexigenic effect and reduces
food intake3. In addition to the effect on appetite, the effect of
nesfatin-1 on mood is also remarkable. It has been shown that the
intracerebroventricular administration of nesfatin-1 can stimulate
the HPA axis4 and increases anxiety, depression-like behavior, and
anhedonia in normal-weight rats5. The relationship between the
nesfatin-1 levels and major depressive disorder, especially among
the adult population, has been mentioned in several studies6.
Depressive disorders in childhood and adolescence have been
characterized by persistent and pervasive anhedonia, sadness,
boredom, or irritability that cause functional impairment7. The
prevalence of depressive disorders is 3-8% in adolescents8. In
Turkey, the prevalence of any mood disorders reported as 2.5%, and
the prevalence of major depressive disorder was reported as 1.7%
in a relatively young sample9. In addition to being a psychiatric
disorder, there has been a lot of evidence that emphasizes the
relationship between major depressive disorder and metabolic
system. The effects of some peptide hormones that affect the
hypothalamus have been studied in recent years. Hypothalamus is
an important target because the areas which are related to mood
(i.e. raphe and arcuate nucleus) exist in the hypothalamus and the
HPA axis is an important factor for depression and anxiety. Leptin
is one of the most studied hormone derived from adipose tissue and
it has effects both on mood and appetite11.
There is a relationship between appetite-related peptide
hormones and major depressive disorder among adolescents.
Nesfatin-1 is a novel candidate molecule in this area. In this study,
we aimed to investigate the relationship between serum nesfatin-1
levels and major depressive disorder among adolescents diagnosed
with major depressive disorder. We hypothesized that there could
be an association between nesfatin-1 and major depressive disorder
among adolescents like adults.

Address for correspondence: S. Burak Acikel MD, Department of Child and Adolescent Psychiatry, Dr. Sami Ulus Maternity and Child Health Hospital, Babur Street No: 44 Altindag Ankara, Turkey, Tel:
+90 544 860 23 16; Fax: +90 312 305 62 36; E-mail: acikel42@gmail.com
17 Burak Acikel S / Arch Clin Psychiatry. 2021;48(1): 16-19

Methods 617.3-50,000pg/mL. The standard curve concentrations used for

the ELISA’s were 50,000pg/mL, 16,666.7pg/mL, 5,555.6pg/mL,
Sample 1,851.9pg/mL, 617.3pg/mL. Samples were assayed in duplicate. The
This study has been conducted at Necmettin Erbakan University, serum nesfatin-1 concentration values are reported in picogram per
Meram School of Medicine, Child and Adolescent Psychiatry milliliter (pg/mL). Blood samples were obtained in empty vacuum
Department outpatient unit. The diagnostic evaluation has been tubes after overnight fasting. Serum samples were obtained after
made according to the DSM 5 diagnostic criteria with the K-SADS- suitable centrifugation and samples were stored at -80oC in a freezer
PL Turkish version12 formed by a child and adolescent psychiatrist until the day of serum nesfatin-1 analysis.
(BA and EH). A total of 30 patients between the ages of 12 and
Statistical Analysis
18 with primary diagnosis of major depressive disorder have been
included in the study. All the patients were at the first depressive The analysis of the data has been performed by using a Statistical
episode when they were included in the study. The following Package programmer for Social Sciences (SPSS) 20.0 statistical
conditions have been considered as exclusion criteria because software (Chicago, IL, USA). The normal distribution of the data
of the potential confounding effect of medical treatment on the was evaluated with the skewness and kurtosis value15. The Student's
nesfatin-1 levels; having psychiatric treatment in the last 3 months; t-test was used in analyzing the differences of psychiatric test
an additional medical condition (disorders that affect the hormonal scores between groups because the normality of the distribution of
system such as diabetes mellitus, thyroid disorders, adrenal system variables is acceptable. Pearson correlation analysis has been used
disorders, long-term medical follow-up, and treatment); diagnosed in investigating the relationship between serum nesfatin-1 levels
with neurodevelopmental disorders such as autism, schizophrenia, and depressive scores. A two-tailed p-value of 0.05 is considered to
bipolar disorder, and intellectual disability; and any other be statistically significant.
psychiatric disorders and treatment. The control group (n=30)
consists of age and sex equalized adolescents and families, without Results
any psychiatric disorder. They were included in the research as the
study group that applied to the Department of Pediatrics Outpatient The study sample consists of 60 adolescents. 30 (4 male, 26 female)
Unit at Necmettin Erbakan University and they have no psychiatric of them have been diagnosed with major depressive disorders and
comorbidity. Also, the diagnostic evaluation has been made with 30 (7 male, 23 female) of them are healthy controls. There are no
the K-SADS-PL Turkish version to a healthy control group formed significant differences between the patient and the control groups
by a child and adolescent psychiatrist. Informed consent was in terms of gender, age, and body-mass index. The mean BMI is
provided with both the patient and the control groups. This study 21.38±4.89 in patient groups and 21.15±4.37 in the control group
has also been approved by Necmettin Erbakan University Ethical (t=0.192, p=0.848). The comparisons of sex, age, and body-mass
Committee (Protocol number: 2016/753). index are given in Table 1.
Tools The mean CDI scores (30.40±6.91 in the patient group, and
Depressive scores of both groups were measured by the Children’s 11.03±6.60 in the control group) were statistically higher in the
Depression Inventory (CDI). CDI is a self-assessment scale patients with MDD than in the control group (t=10.998, p<0.001)
applicable to children between the ages of 6 and 17. For this (Table 2) The mean serum nesfatin-1 levels in the patients with
study, the scale has been filled in by the child him/herself. There MDD was 40.11±1.62 pg/ml, whereas it was 37.51±5.10 pg/ml in
were three different options for each item on the 27-point scale. healthy controls. The difference of mean serum nesfatin-1 levels
The child is asked to choose the most appropriate sentence for the between groups was statistically significant (t=2.66, p=0.04, cohen’s
last two weeks. Each item takes 0, 1, or 2 points according to the d=0.538). The serum nesfatin-1 levels values are given in Table 2.
severity of the indication. The highest score is 54. The higher the In the patient group, there is a positive correlation between
score, the greater the depression is13. The validity and reliability of serum nesfatin-1 levels and CDI scores, and this relationship is
the inventory in Turkish have also been formed14. The cut point is nearly statistically significant (p=0.05, r=0.349).
recommended as 19.
Physical measurement (weight and height measurements and
calculation of body mass indexes (BMI)) of all participants were Table 1. Comparison of sex, age and body-mass index
done studiously by the same measure and digital scales.
Demographics Patient Control Statistics
Biochemical Measurements N % N % x2 p
Blood samples for nesfatin-1 were obtained in the morning around Sex (Male/Female) 4/26 13.3/86.7 7/23 23.3/76.7 1.002 0.317
9 a.m. from a forearm vein of the participants at the end of an Mean SD Mean SD t p
overnight 10 hours fasting period at least. Then the blood was Age 15.63 1.51 15.30 1.66 0.810 0.421
carefully and immediately (in a few seconds) transferred from BMI 21.38 4.89 21.15 4.37 0.192 0.848
the blood tubes to centrifuge tubes. After the centrifuge process, BMI: Body mass index
the separated serum was stored at −80°C, in a freezer until the
time of assay. Serum nesfatin-1 concentrations were measured
by a commercially available kit based on the enzyme-linked
Table 2. Comparison of depressive scores and serum Nesfatin 1 Level
immunosorbent assay (ELISA) method (Human Nesfatin 1 ELISA
Kit, Uscn Life Science, Wuhan, PR China). The assay uses a two- Patient Control Statistics
side sandwich technique with two selected polyclonal antibodies Mean SD Mean SD t p Cohen’s d
that bind to different epitopes of human nesfatin-1. The minimum CDI Scores 30.40 6.91 11.03 6.60 10.998 <0.001** 2.867
detectable dose (sensitivity) of nesfatin-1 with ELISA kit is typically Nesfatin-1
less than 234.2pg/mL. This assay has high sensitivity and excellent Levels (pg/ 40.11 1.62 37.51 5.10 2.076 0.04* 0.538
specificity for detection of nesfatin-1. The detection range of kit is ml)
 Burak Acikel S / Arch Clin Psychiatry. 2021;48(1): 16-19
Discussion
Our study has been the first that investigates the relationship
between serum nesfatin-1 levels and major depressive disorder
among adolescents. It has been found that serum nesfatin-1 levels
are significantly higher in patients than in healthy controls. In
the patient group, there is a nearly statistically significant positive
correlation between serum nesfatin-1 levels and depressive
symptoms.
There have been several studies that investigate the relationship
between nesfatin-1 levels and major depressive disorder among
adults. In these studies, higher mean plasma levels of nesfatin-1
were found in depressed patients16,17. In addition to these findings,
it has been found that plasma nesfatin-1 levels were associated with
depression severity. Moreover, it was an independent indicator of
severe depression18. Consistent with these findings, we have found a
higher serum nesfatin-1 levels in patients and a positive correlation
between serum nesfatin-1 levels and depressive symptoms. This
has been the first finding about the relationship between serum
nesfatin-1 levels and major depressive disorder among adolescents.
In the literature, there have also been some animal studies
investigating the relationship between nesfatin-1 and major
depressive disorder. Among rats, intraperitoneal injection of
nesfatin-1 increased the depressive behaviors. For instance; it
increased the immobility in the forced swim test and decreased the
swimming time19. In addition to this, plasma interleukin 6 and CRP
levels which are important cytokines for depression20 increased the
dose-dependently19. In a recent study, nesfatin-1, corticosterone,
interleukin 6, and CRP levels have been found significantly higher in
patients with the major depressive disorder than controls. A positive
correlation has been found between nesfatin-1, interleukin 6, and
CRP concentrations21. So, it could be mentioned that nesfatin-1
might activate the immune system and cytokines and might trigger
depression. In our sample, we have found a higher serum nesfatin-1
levels in the patient group and a positive correlation between serum
nesfatin-1 levels and depressive symptoms.
We think that it is important to state the pathophysiological
meaning of the change of nesfatin-1 levels in depression. There
have been few studies that indicate the interaction between
nesfatin-1 and the serotoninergic system which has an important
role on depression pathophysiology. 5HT 1B/2C agonism results
in anorexigenic effect by upregulating NUCB2 expression in the
hypothalamus. Besides that, the activation of 5HT 2C receptors
might play a role in regulating NUCB2 expression and feeding
behavior22. It is shown that inverse agonism of 5HT 2C receptor
via olanzapine decreases the NUCB2/nesfatin-1 expression in
hypothalamic feeding-related areas of rats. This effect results in
increased food intake and weight gain23. So, it could be mentioned
that the serotonin 5HT2C receptor has an important effect on
nesfatin-1 expression. It is also known that 5-HT2C receptor
blockade has a reducing effect on depressive and anxious states24.
Therefore, it could be suggested that 5-HT2C antagonism decreases
the nesfatin-1 levels and at the same time it has an antidepressant
effect. This relationship could explain the inverse relationship
between nesfatin-1 levels and depression. Longitudinal studies
are needed to examine whether increased nesfatin-1 levels are the
cause or the effect of mood disorders.
There is a close relationship between depression and obesity.
Obesity and being overweight are positively associated with
depression in adolescents25. Furthermore, the psychological and
social difficulties (i.e decreased self-esteem, problems in social
interaction, social rejection, and bullying) in obesity could increase
the depressive mood26. It can be stated that there has been a bi-
directional relationship between obesity and depression. In obese
18
adolescents, serum nesfatin-1 levels have been found higher
compared to non-obese adolescents. In this study, it has been
suggested that the efficiency of nesfatin-1 is reduced in obese
individuals due to the saturation of transporters that transport
nesfatin-1 from blood to cerebrospinal fluid. (CSF)27. When we
consider the bi-directional relationship between obesity and
depression, it might be mentioned that the reduced nesfatin-1
efficiency in the central nervous system might result in both obesity
and depression. Nesfatin-1 could be a biological junction in the
depression and obesity relationship.
This study has certain limitations. The small sample size is the
main limitation of our study. It is not clear whether the measure of
nesfatin-1 levels from peripheral blood reflects its levels in the brain
or not. Serum nesfatin-1 levels were measured by only the ELISA
method but not confirmed through any other method (Western
blot, etc). This should be mentioned as a methodological limitation.
We haven’t been able to establish causality between nesfatin-1 levels
and depression because of the cross-sectional design of our study.
Several confounding factors that change in depression such as BMI
or eating behaviors couldn’t be analyzed in this cross-sectional
study. Future longitudinal studies are going to be useful to clarify
the variability of nesfatin-1 levels according to the variability of
symptoms and related behaviors.
As a conclusion, this is the first study to examine the relationship
between major depressive disorder and serum nesfatin-1 levels
among ciladolescents diagnosed with major depressive disorder.
Conflict of interest statement: There is no conflict of interest to
declare
Funding: There is no funding source for this research. All materials
required for the study were provided by the authors.
This study was conducted in Necmettin Erbakan University,
Meram School of Medicine Department of Child and Adolescent
Psychiatry, Konya TURKEY
References
1. Oh-I S, Shimizu H, Satoh T, Okada S, Adachi S, Inoue K, et
al. Identification of nesfatin-1 as a satiety molecule in the
hypothalamus. Nature. 2006;443(7112):709–12.
2. Ayada C, Toru Ü, Korkut Y. Nesfatin-1 and its effects on different
systems. Hippokratia. 2015;19(1):4–10.
3. Stengel A, Taché Y. Nesfatin-1. In: Handbook of Biologically
Active Peptides. Second Edi. Elsevier Inc.; 2013. p. 850–5.
4. Stengel A, Goebel M, Wang L, Rivier J, Kobelt P, Mönnikes
H, et al. Central nesfatin-1 reduces dark-phase food intake
and gastric emptying in rats: differential role of corticotropin-
releasing factor2 receptor. Endocrinology. 2009;150(11):4911–9.
5. Kühne S, Schalla M, Friedrich T, Kobelt P, Goebel-Stengel M,
Long M, et al. Nesfatin-130-59 Injected Intracerebroventricularly
Increases Anxiety, Depression-Like Behavior, and Anhedonia in
Normal Weight Rats. Nutrients. 2018;10(12):1889.
6. Caroleo M, Carbone EA, Primerano A, Foti D, Brunetti
A, Segura-Garcia C. The role of hormonal, metabolic and
inflammatory biomarkers on sleep and appetite in drug free
patients with major depression: A systematic review. J Affect
Disord. 2019;250:249–59.
7. Birmaher B, Brent D. Depressive and Disruptive Mood
Dysregulation Disorders. In: Dulcan’s Textbook of Child and
Adolescent Psychiatry. American Psychiatric Association
Publishing; 2016.
8. Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A. Prevalence
and Development of Psychiatric Disorders in Childhood and
Adolescence. Arch Gen Psychiatry. 2003;60(8):837.
19 Burak Acikel S / Arch Clin Psychiatry. 2021;48(1): 16-19
9. Karacetin G, Arman AR, Fis NP, Demirci E, Ozmen S,
Hesapcioglu ST, et al. Prevalence of Childhood Affective
disorders in Turkey: An epidemiological study. J Affect Disord.
2018;238:513–21.
10. Hryhorczuk C, Sharma S, Fulton SE. Metabolic disturbances
connecting obesity and depression. Front Neurosci. 2013;7.
11. Carvalho-Ferreira JP de, Masquio DCL, Campos RM da S,
Netto BDM, Corgosinho FC, Sanches PL, et al. Is there a role for
leptin in the reduction of depression symptoms during weight
loss therapy in obese adolescent girls and boys? Peptides. 2015
Mar;65:20–8.
12. Ünal F, Öktem F, Çuhadaroğlu FÇ, Kültür SEÇ, Akdemİr D,
Özdemİr DF, et al. Reliability and Validity of the Schedule for
Affective Disorders and Schizophrenia for School-Age Children-
Present and Lifetime Version, DSM-5 November 2016-Turkish
Adaptation (K-SADS-PL-DSM-5-T). 2019;30(1):42–50.
13. Kovacs M. The Children’s Depression, Inventory (CDI).
Psychopharmacol Bull. 1985;21(4):995–8.
14. Öy B. Çocuklar için depresyon ölçeği: Geçerlilik ve güvenirlik
çalışması [The validity and reliability study of the Turkish
version of children’s depression inventory]. Turkish J Psychiatry.
1991;2(2):132–6.
15. George D, Mallery P. Descriptive Statistics: Measures of central
tendency, variability, deviation from normality, size, and
stability. In: SPSS for Windows Step by Step: A Simple Guide
and Reference. 11th ed. 2003. p. 95–105.
16. Algul S, Ozcelik O. Evaluating the Levels of Nesfatin-1 and
Ghrelin Hormones in Patients with Moderate and Severe
Major Depressive Disorders. Psychiatry Investig. 2018 Feb
25;15(2):214–8.
17. Ari M, Ozturk OH, Bez Y, Oktar S, Erduran D. High plasma
nesfatin-1 level in patients with major depressive disorder. Prog
Neuro-Psychopharmacology Biol Psychiatry. 2011;35(2):497–
500.
18. Xiao M-M, Li J-B, Jiang L-L, Shao H, Wang B-L. Plasma
nesfatin-1 level is associated with severity of depression in
Chinese depressive patients. BMC Psychiatry. 2018;18(1):88.
19. Ge J-F, Xu Y-Y, Qin G, Peng Y-N, Zhang C-F, Liu X-R, et al.
Depression-like Behavior Induced by Nesfatin-1 in Rats:
Involvement of Increased Immune Activation and Imbalance of
Synaptic Vesicle Proteins. Front Neurosci. 2015;9:429.
20. Valkanova V, Ebmeier KP, Allan CL. CRP, IL-6 and depression:
a systematic review and meta-analysis of longitudinal studies. J
Affect Disord. 2013;150(3):736–44.
21. Xia Q-R, Liang J, Cao Y, Shan F, Liu Y, Xu Y-Y. Increased plasma
nesfatin-1 levels may be associated with corticosterone, IL-6,
and CRP levels in patients with major depressive disorder. Clin
Chim Acta. 2018;480:107–11.
22. Nonogaki K, Ohba Y, Sumii M, Oka Y. Serotonin systems
upregulate the expression of hypothalamic NUCB2 via 5-HT2C
receptors and induce anorexia via a leptin-independent pathway
in mice. Biochem Biophys Res Commun. 2008;372(1):186–90.
23. Rojczyk E, Pałasz A, Wiaderkiewicz R. Effect of short and
long-term treatment with antipsychotics on orexigenic/
anorexigenic neuropeptides expression in the rat hypothalamus.
Neuropeptides. 2015;51:31–42.
24. Millan MJ. Serotonin 5-HT2C receptors as a target for the
treatment of depressive and anxious states: focus on novel
therapeutic strategies. Therapie. 2015;60(5):441–60.
25. Quek Y-H, Tam WWS, Zhang MWB, Ho RCM. Exploring the
association between childhood and adolescent obesity and
depression: a meta-analysis. Obes Rev. 2017;18(7):742–54.
26. Djalalinia S, Qorbani M, Peykari N, Kelishadi R. Health impacts
of Obesity. Pakistan J Med Sci. 2015;31(1):239–42.
27. Anwar GM, Yamamah G, Ibrahim A, El-Lebedy D, Farid TM,
Mahmoud R. Nesfatin-1 in childhood and adolescent obesity
and its association with food intake, body composition and
insulin resistance. Regul Pept. 2014;188:21–4.
 Review article

Comparison of prolactin level in schizophrenia patients treated with risperidone oral or

long-acting injections – preliminary report
Anna Skowrońska1,2

Dominik Strzelecki2

Adam Wysokiński1

Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Poland
1

Department of Affective and Psychotic Disorders, Medical University of Łódź, Łódź, Poland
2

Received: 16-08-2019 – Accepted: 07-10-2020

DOI: 10.1590/0101-60830000000273

ABSTRACT
Introduction: Hyperprolactinemia is a significant side effect of antipsychotic therapy. Risperidone, commonly used antipsychotics, is
available in oral tablets and long-acting injections (LAI). This study aimed to investigate a potential difference in terms of prolactin levels
among patients treated with these formulations of risperidone.
Method: This was a naturalistic, retrospective, cross-sectional study. 91 patients with schizophrenia treated with risperidone in monotherapy
were included into the study. 72 patients were treated with the oral form and 19 patients were treated with LAI form. All subjects had one
measurement for prolactin level.
Results: Our results showed that a mean dose of prolactin was significantly higher in the RIS- oral group and the difference was significant
(p=0.019). There was no difference (p=0.59) in the percentage of patients with hyperprolactinemia in both study groups but more
patients in the RIS-oral group had severe hyperprolactinemia and fewer patients in the RIS-oral group had mild hyperprolactinemia.
Hyperprolactinemia was the main reason for discontinuation of treatment in the RIS-LAI group.
Conclusions: According to the data from our study two forms of risperidone may differ in terms of impact on prolactin levels. Patients
treated with LAI risperidone may have prolactin levels lower than on the oral form.

Skowrońska A / Arch Clin Psychiatry. 2021;48(1):20-23

Keywords: schizophrenia; risperidone; prolactin; long-acting injections

Introduction treatment. It provides a better pharmacokinetic profile, which

Schizophrenia is a chronic and recurrent psychiatric disorder that
requires a long-term treatment with antipsychotics. It is a complex
disorder associated with high rates of noncompliance and treatment
discontinuation1. There are many factors influencing compliance
in schizophrenia, such as medication side effects, insight, access
to treatment or, social support2. The introduction of long-acting
injections (LAI) antipsychotics has shown the improvement of
compliance, reduction of relapses and hospitalization rates3,4.
Randomized studies suggest that some LAIs may be also associated
with fewer side effects compared with their oral forms5,6.
Risperidone is an older (introduced in 1993) second-generation
antipsychotics, but due to its good efficacy and safety profile, it
remains one of the most frequently prescribed antipsychotics
for schizophrenia. Long-acting risperidone was the first long-
acting injectable atypical antipsychotic. Experimental studies
suggest that treatment with risperidone LAI is more effective
than the oral form in improvement in clinical symptoms and
functioning, reduction in a number of rehospitalization, and
better adherence. The risperidone LAI, like other LAI, ensures
a better bioavailability, because the correlation between drug
dose and plasma concentrations is more predictable during the
allows to use of lower doses and to reduce the risk of side effects7-10.
The common side-effects of risperidone LAI, except for an
injection site pain, are consistent with those associated with oral
risperidone: hyperprolactinemia, extrapyramidal symptoms and
sedation. Furthermore, experimental studies have confirmed that
risperidone treatment may induced weight gain and disturbed
glucose homeostasis, what can result in metabolic syndrome also in
children and adolescent population11,12. Interestingly, some studies
suggest, that the frequency of some side effects may be lower for
long-acting risperidone than oral risperidone10,13.
Hyperprolactinemia (hPRL) is the elevation of blood prolactin
level. It is a significant side effect, which may result in non-
compliance and treatment discontinuation. It is due to secondary
sexual dysfunctions, which are often unacceptable by the patients.
In patients treated with antipsychotics hyperprolactinemia usually
results from the blockage of dopamine type 2 receptors (D2) in
the anterior pituitary lactotrophic cells. Prolactin (PRL) elevation
during antipsychotic treatment is mostly correlated with the affinity
of an antipsychotic for dopamine D2 receptors and their blood-brain
barrier penetrating ability. Of all second- generation antipsychotics,
risperidone has one of the highest potential for PRL elevation13. This
may potentially limit its use in many patients, especially in women.

Address for correspondence: Adam Wysokiński M.D., Ph.D., Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Czechosłowacka 8/10, 92-216 Łódź, Poland. Tel.:
+48 42 675 73 72; Fax: +48 42 675 77 29; E-mail: adam.wysokinski@umed.lodz.pl
21 Skowrońska A / Arch Clin Psychiatry. 2021;48(1): 20-23
Interestingly, recent meta-analyses revealed that breast cancer is
probably more common in female patients with schizophrenia
than in the general population and there may be a link between
antipsychotic- induced hyperprolactinemia and breast cancer risk
in women with schizophrenia14-16. It is worth noting that several
studies on hyperprolactinemia have been conducted in children
and adolescents populations with autism spectrum disorder
treated with risperidone17,18. The results confirmed that risperidone
treatment could cause hyperprolactinemia also in this population.
The authors have suggested that the effects of risperidone on
prolactin were probably dose-related in pediatric patients.
This study was aimed at comparing the prolactin level in
schizophrenia patients treated with oral risperidone or long-acting
injections risperidone. Although similar studies have already
been published, this study provides still valuable clinical data as it
indicates the consistent conclusion.
Material and methods
Data sources
This was a naturalistic, retrospective, cross-sectional study. Data
from years 2011-2018 was collected. Our psychiatry clinical
hospital electronic database was screened for adult Caucasian
patients with schizophrenia, treated with risperidone oral (the RIS-
oral group) or long-acting injections (the RIS-LAI group), who had
at least one measurement for PRL level. All study subjects were on
antipsychotic monotherapy with risperidone.
Study subjects
All study subjects were diagnosed as paranoid schizophrenia
according to Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-V). 91 patients with schizophrenia treated
with risperidone in monotherapy were included into the study.
72 patients were treated with the oral form and 19 patients were
treated with LAI form. All study subjects were taking risperidone
as the only antipsychotic drug. Pregnant women, patients with
acromegaly and other conditions known to elevate PRL level, and
patients taking medications other than risperidone that may affect
PRL level (e.g. anticonvulsants, antihistamines, antihypertensives,
oestrogens, opiates) were excluded from the study.
Prolactin level determination
Blood samples for PRL test were drawn for all patients between
8 and 9 a.m. after 12 hours overnight fast. Immediately after
collecting blood samples, concentration of PRL (expressed in ng/
mL) was determined using the Architect i1000SR Immunoassay
Analyzer (Abbott, USA). Normal level of prolactin was defined as
25 ng/mL (19).
Statistical analysis
Statistical procedures were performed with STATA 15.1 (StataCorp,
USA). Simple descriptive statistics (mean ± standard deviation)
were generated for continuous variables. For discrete variables
number of patients and percentages are given. Normality of
distribution was tested with Shapiro-Wilk test. Level of prolactin
was highly skewed, but after square root transformation it followed
normal distribution. For statistical analysis one-way ANOVA and
t-test were used. The difference between proportions was analysed
with the Fisher's exact test. Associations were tested by Pearson's
correlation coefficient. Odds ratios (OR) with 95% confidence
intervals (95% CI) were calculated using logistic regression. The
level of significance was set at p <0.05 (two-sided).
Ethical standards
The study has been approved by the appropriate ethics. The authors
assert that all procedures contributing to this work comply with
the ethical standards of the relevant national and institutional
committees on human experimentation and with the Helsinki
Declaration of 1975, as revised in 2008.
Results
There were 72 patients in the RIS-oral and 19 in the RIS-LAI groups.
Summary of the demographic and clinical data is shown in Table 1.
There was no difference between age of men and women, p = 0.78.
Daily dose of risperidone LAI was calculated as LAI dose divided
by 14 (number of days between consecutive injections). Low dose
was defined as 1-2 mg/d for risperidone oral and 25 mg/14 days
for risperidone LAI; medium dose: 3-4 mg/d for risperidone oral
and 37.5 mg/14 days for risperidone LAI; high dose: 5-6 mg/d for
risperidone oral and 50 mg/14 days for risperidone LAI. Detailed
risperidone treatment data is also shown in Table 1.
Mean level of prolactin was significantly higher in the RIS-
oral group (99.63±69.09 ng/mL vs. 62.19±38.81 ng/mL) and the
difference was significant (p = 0.014) with corresponding Cohen's
d effect size of 0.58. When this comparison was adjusted for age
and a dose of risperidone, the difference remained significant
(100.42±7.49 vs. 59.17±14.70 ng/mL, p = 0.014), see Figure 1.
However, as there were more women in the study groups (although
there were no differences in the percentage of men and women
between the RIS-oral and RIS- LAI groups, p = 0.28) we have
reanalysed the difference adjusting for age, dose of risperidone and
sex. This way adjusted mean level of prolactin was still higher in
the RIS-oral group (98.21±6.93 vs. 67.56±13.71 ng/mL), but the
difference was of borderline non-significance (p = 0.051). There
was no difference (p = 0.59) in the percentage of patients with hPRL
in both study groups (RIS-oral: 68, 94.4% vs. RIS-LAI: 16, 88.9%).
However, significantly more patients in the RIS-oral group had
severe hPRL (RIS-oral: 32, 47.1% vs. RIS-LAI: 2, 12.5%) and less
patients in the RIS-oral group had mild hPRL (RIS-oral: 13, 19.1%
vs. RIS-LAI: 6, 37.5%), p = 0.027, see Figure 2.
No patients in the RIS-LAI and 5 (6.9%) patients in the RIS-
oral group were taking bromocriptine due to hPRL (p = 0.58). After
excluding the patients taking bromocriptine from the analysis,
the difference between RIS-oral and RIS-LAI was still significant
(p = 0.019). No other dopamine-agonists were used by the study
patients. Risperidone was discontinued in 6 (33.3%) and 41 (56.9%)
of the patients in the RIS-LAI and RIS-oral groups, respectively (p =
Table 1. Summary of the demographic and clinical data.
risperidone oral risperidone p
(n = 72) LAI (n = 19)
age [y] 36.7±10.9 37.8±8.8 0.69
women 51 (70.8%) 10 (55.6%) 0.26
risperidone mean daily
3.78±1.50 3.12±0.55 0.07
dose [mg]
17 (23.6%) 1 (5.6%)
risperidone dose: low
21 (29.2%) 7 (38.9%) 0.08
moderate high
34 (47.2%) 10 (55.6%)
prolactin [ng/mL]* 99.63±69.09 62.19±38.81 0.014
treatment with
0 5 (6.9%) 0.58
bromocriptine
Data presented as mean±standard deviation or absolute number
(percentage).
* unadjuste
 Skowrońska A / Arch Clin Psychiatry. 2021;48(1): 20-23
150 p = 0.014
serum PRL [mg/mL]
100
50
0
RIS-oral RIS-LAI
Figure 1. Adjusted (for age and risperidone dose) level of prolactin in the study
groups.
PRL: prolactin; RIS-oral: patients taking oral risperidone; RIS-LAI: patients taking
long-acting injections of risperidone.
Vertical bars indicate standard deviations.
100
%
50
0 that it is the metabolite 9-hydroxyrisperidone which is the main
RIS-oral RIS-LAI
severe moderate mild
Figure 2. Severity of hyperprolactinemia in the study groups
RIS-oral: patients taking oral risperidone; RIS-LAI: patients taking long-acting
injections of risperidone.risperidone.
0.11). In the RIS-LAI group the major reason for discontinuation
was the lack of clinical effectiveness (3, 50.0%), while in the RIS-
oral group hPRL was the major reason (25, 61.0%).
In the RIS-LAI group we were able to identify 2 subjects with
other potential causes for altered PRL level (past treatment with
zuclopenthixol or haloperidol) and 7 subjects in the RIS-oral group
(past treatment with amisulpride, haloperidol and post-stroke
pituitary insufficiency). When we have excluded these patients
from analysis, the difference between both study groups in terms
of PRL level remained significant (RIS-oral: 92.03±54.77, RIS- LAI:
64.06±41.25 ng/mL, p = 0.047).
Interestingly, in our study women had lower risk for hPRL (OR
0.2, 95% CI 0.07- 0.59, p = 0.003). Compared with the RIS-oral
group, in the RIS-LAI group OR for hPRL was 0.5 (95% CI 0.08-
2.96), the result was not statistically significant (p = 0.44). However,
the RIS-LAI group had significantly lower risk of severe hRPL (OR
0.25, 95% CI 0.03-0.68, p = 0.015) and there were no differences for
risk of mild or moderate hPRL. Medium dose of risperidone was
associated with the highest risk of moderate hPRL (OR 5.7, 95%
CI 1.36-23.46, p = 0.017), while in the high dose of risperidone
group the risk of severe hPRL was reduced (OR 0.1, 95% CI 0.03-
0.45, p = 0.002).
22
Discussion
In this preliminary study two forms of risperidone (LAI and
oral) differed in terms of impact on prolactin levels. Although
the frequency of hyperprolactinemia was similar in both groups,
the mean dose of prolactin (in blood) was significantly higher in
patients taking the oral form of risperidone. Moreover, a higher
number of patients in this group had severe hyperprolactinaemia.
Significantly, hyperprolactinemia was the major reason for
discontinuation of treatment in the RIS-oral group. It is worth
noting that the high prolactin levels can trigger clinically
significant symptoms like: oligomenorrhea, amenorrhea,
galactorrhoea, decreased libido in women and erectile dysfunction,
decreased libido, infertility and gynecomastia in men, which can
be unacceptable for some patients20. An augmentation with a
dopamine agonist (such as bromocriptine) may be considered
in patients without severe symptomatic hyperprolactinemia and
with stable control of psychotic symptoms. It is worth pointing
out that in our study no patient in the RIS-LAI group and only
5 (6.9%) patients in the RIS-oral were taking bromocriptine due
to hyperprolactinemia. This data would seem to suggest that the
prescribing of bromocriptine is still rare in clinical practice, at least
among in-hospital subjects.
The differences in prolactin levels between RIS-oral and RIS-
LAI group reported in our results are congruent with reported in
other studies21-24. The difference in prolactin levels for these two
forms of administration may be explained by the differences in
pharmacokinetics of these two forms of risperidone. Firstly, during
treatment with long-acting risperidone peak-trough fluctuations
are reduced compared to oral risperidone, what can suggest a
correlation between changes in prolactin levels and peak-trough
fluctuations of risperidone. Secondly, the long-acting and oral
risperidone differ in serum concentrations of risperidone and its
major metabolite 9-OH risperidone (paliperidone)25. It is possible,
reason for the increased serum prolactin level, what was suggested
in some studies26,27. The study results showed that the plasma
concentration of 9-hydroxy-risperidone, but not of risperidone
were significantly correlated with increases prolactin level in
plasma26,27. Our finding that patients taking a medium dose of
risperidone has the highest increase in the risk of hPRL indicates
that this sub-population should be particularly carefully monitored
for hPRL, even though they may present no hPRL symptoms. In our
study women had a lower risk for hPRL. This is interesting because
it is found that hyperprolactinemia secondary to antipsychotic
medication is greater in females than in males and it is due to the
ability of the estrogens to elevate PRL levels28. The potential cause
of these differences can be a high mean age of women in our study
(39.7 years). It is known that postmenopausal women experience
pharmacologically induced hyperprolactinemia less frequently
than women of reproductive age29. Moreover, some studies have
also showed that in women using hormonal contraception the
increase in prolactin was significantly greater than in those without
estrogen supply30.
In recent years, some studies have pointed out that polymorphism
in dopamine and serotonin receptors could be associated with
reduced receptor density what can be essential for drug efficacy and
drug-induced side effects like hyperprolactinemia31,32. Furthermore,
the few studies have also identified specific variants of the DRD2
gene which could be useful in predicting the development of
hyperprolactinemia during risperidone treatment both in adults
and children populations33,34.
As mentioned, this is a preliminary study, hence it has some
potential limitations. First of all, the number of the RIS-LAI
23 Skowrońska A / Arch Clin Psychiatry. 2021;48(1): 20-23
subjects is low thus limiting the power of statistical tests. Also,
there is a potential risk of selection bias, i.e. patients with confirmed
hPRL while on oral risperidone would be unlikely switched to LAI
risperidone. However, PRL tests are not done on a routine basis in
the hospital unit the study patients were hospitalized in, therefore
this would apply mostly to patients with symptomatic hRPL.
Secondly, the serum prolactin levels were assessed only once, we
did not analyze longitudinal changes of plasma prolactin levels
before initiating the treatment with risperidone and in the course
of switching from oral risperidone to LAI risperidone. This serious
limitation has to be taken into consideration. Thirdly, patients
were on antipsychotic monotherapy, but some of them received
other psychopharmacological treatments like antidepressants or
mood stabilizers, though these should not affect prolactin levels
significantly. Finally, there was a discrepancy in number of subjects
in both groups (the LAI group was significantly smaller), which
reflects that LAI risperidone (as well as other LAI antipsychotics) is
still infrequently prescribed to schizophrenia patients.
Despite these limitations, the findings of this study demonstrate
the possible relationship between prolactin level and the form of
risperidone. Considering its preliminary character the results
must be interpreted with caution, but they indicate that patients
with schizophrenia that are treated with LAI risperidone may have
serum prolactin levels lower compared with patients treated with
the oral form. Therefore, taking LAI risperidone may be more
advantageous than the oral form in terms of impact on prolactin
levels. This observation may be highly useful in clinical practice.
Further and more detailed follow-up studies ought to be conducted
to confirm our results.
References
1. Young JL, Zonana HV, Shepler L. Medication noncompliance in
schizophrenia: codification and update. Bull Am Acad Psychiatry Law
1986;14:105-122.
2. Perkins DO. Predictors of Noncompliance in Patients With
Schizophrenia. J Clin Psychiatry 2002;63(12):1121-1128.
3. Leucht C, Heres S, Kane JM, et al. Oral versus depot antipsychotic drugs
for schizophrenia – a critical systematic review and meta-analysis of
randomized long- term trials. Schizophrenia Research 2011;127:83-92.
4. Davis JM, Matalon L, Watanabe MD, Blake L. Depot antipsychotic
drugs: place in therapy. Drugs 1994;47:741-743.
5. Zhornitsky S, Stip E. Oral versus Long-Acting Injectable Antipsychotics
in the Treatment of Schizophrenia and Special Populations at Risk
for Treatment Nonadherence: A Systematic Review. Schizophrenia
Research and Treatment 2012;2012:407171.
6. Ostuzzi G, Giovanni I, So R, et al. Does formulation matter? A systematic
review and meta- analysis of oral versus long-acting antipsychotic
studies. Schizophrenia Research 2017;183 ,10-21.
7. Gutiérrez-Casares JR, Cañas F, Rodríguez-Morales A, Hidalgo-Borrajo
R, Alonso- Escolano D. Adherence to treatment and therapeutic
strategies in schizophrenic patients: the ADHERE study. CNS Spectr
2010;15(5):327–337.
8. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable
risperidone: efficacy and safety of the first long-acting atypical
antipsychotic. Am J. Psychiatry 2003;160:1125-1132.
9. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of
schizophrenia with long-acting risperidone: a 12-month evaluation of
the first long-acting second- generation antipsychotic. J. Clin. Psychiatry
2003;64:1250-1257.
10. Chue P, Eerdekens M, Augustyns I, et al. Comparative efficacy and
safety of long- acting risperidone and risperidone oral tablets. European
Neuropsychopharmacology 2005;15(1):111–117.
11. Gautam S, Meena PS. Drug-emergent metabolic syndrome in
patients with schizophrenia receiving atypical (second-generation)
antipsychotics. Indian J Psychiatry. 2011;53(2):128-133.
12. Srisawasdi P, Vanwong N, Hongkaew Y, et al. Impact of risperidone on
leptin and insulin in children and adolescents with autistic spectrum
disorders. Clinical Biochemistry. 2017;50(12):678-685.
13. Peuskens J, Pani L, Detraux J, De Hert M. The Effects of Novel and Newly
Approved Antipsychotics on Serum Prolactin Levels: A Comprehensive
Review. CNS Drugs 2014;28(5):421-453.
14. Wu Chou AI, Wang YC, Lin CL, Kao CH. Female schizophrenia
patients and risk of breast cancer: A population-based cohort study,
Schizophrenia Research 2017;188:165-171.
15. Wang PS, Walker AM, Tsuang MT et al. Dopamine antagonists and
the development of breast cancer. Archives of General Psychiatry
2002;59:1147–1154.
16. Azoulay L, Yin H, Renoux C, Suissa S. The use of atypical antipsychotics
and the risk of breast cancer. Breast Cancer Research and Treatment
2011; 129: 541–548.
17. Hongkaew Y, Ngamsamut N, Puangpetch A, et al. Hyperprolactinemia
in Thai children and adolescents with autism spectrum disorder treated
with risperidone.Neuropsychiatric Disease and Treatment. 2015;11:191-
196.
18. Hongkaew Y, Medhasi S, Pasomsub E, et al. UGT1A1 polymorphisms
associated with prolactin response in risperidone-treated children and
adolescents with autism spectrum disorder. The Pharmacogenomics
Journal. 2018;18(6):740-748.
19. Mancini T, Felipe FC, Giustina A. Hyperprolactinemia and Prolactinomas.
Endocrinology and Metabolism Clinics 2008;37(1):67-99.
20. Majumdar A, Mangal NS. Hyperprolactinemia. Journal of Human
Reproductive Sciences 2013;6(3):168-175.
21. Canuso CM, Bossie CA, Lasser RA, et al. Reduced serum prolactin
levels after treatment with long-acting risperidone. Poster at 156th APA
congress, San Francisco; 2003.
22. Chue P, Eerdekens M, Augustyns I, et al. Comparative efficacy and
safety of long- acting risperidone and risperidone oral tablets. European
Neuropsychopharmacology: the Journal of the European College of
Neuropharmacology 2005;15(1):111–7.
23. Peng PW, Huang MC, Tsai CJ, et al. The disparity of pharmacokinetics
and prolactin study for risperidone long-acting injection. Journal of
Clinical Psychopharmacology 2008;28(6):726–7.
24. Bai YM, Chen TT, Lin WK, et al. Pharmacokinetics study for
hyperprolactinemia among schizophrenics switched from
risperidone to risperidone long-acting injection. Journal of Clinical
Psychopharmacology 2007;27(3):306–8.
25. Nesvag R, Hendset M, Refsum H, et al. Serum concentrations of
risperidone and 9- OH risperidone following intramuscular injection
of long-acting risperidone compared with oral risperidone medication.
Acta Psychiatrica Scandinavica 2006;114:21–6.
26. Knegtering R, Baselmans P, Castelein S, et al. Predominant role of the
9-hydroxy metabolite of risperidone in elevating blood prolactin levels.
American Journal of Psychiatry 2005;162(5):1010–1012.
27. Melkersson KI. Prolactin elevation of the antipsychotic risperidone
is predominantly related to its 9-hydroxy metabolite. Human
Psychopharmacology 2006;21(8):529–32.
28. Veselinovic´ T, Schorn H, Vernaleken IB, et al. Impact of different
antidopaminergic mechanisms on the dopaminergic control of prolactin
secretion. J Clin Psychopharmacol. 2011;31(2):214–20.
29. Kinon BJ, Ahl J, Liu-Seifert H, et al. Prevalence of hyperprolactinemia
in schizophrenic patients treated with conventional antipsychotic
medications or risperidone. Psychoneuroendocrinology. 2003;28(Suppl
2):55–68.
30. Veselinović T, Schorn H, Vernaleken IB, Schiffl K, Klomp M, Gründer G.
Impact of different antidopaminergic mechanisms on the dopaminergic
control of prolactin secretion. J Clin Psychopharmacol. 2011;31(2):214-
220.
31. Miura I, Zhang JP, Hagi K, et al. Variants in the DRD2 locus
and antipsychotic-related prolactin levels: A meta-analysis.
Psychoneuroendocrinology. 2016;72:1-10.
32. Sukasem C, Hongkaew Y, Ngamsamut N, et al. Impact of
Pharmacogenetic Markers of CYP2D6 and DRD2 on Prolactin Response
in Risperidone-Treated Thai Children and Adolescents With Autism
Spectrum Disorders. J Clin Psychopharmacol. 2016;36(2):141-146.
33. Calarge CA, Ellingrod VL, Acion L, et al. Variants of the dopamine D2
receptor gene and risperidone-induced hyperprolactinemia in children
and adolescents. Pharmacogenet Genomics. 2009;19:373–82.
34. Hongkaew Y, Medhasi S, Pasomsub E, et al. UGT1A1 polymorphisms
associated with prolactin response in risperidone-treated children
and adolescents with autism spectrum disorder. Pharmacogenomics J.
2018;18(6):740-748.
 Original article

Relationship between mobile phone addiction and Narcissistic personality disorder

among medical students
Roya Vaziri-Harami1
https://orcid.org/0000-0002-2875-4512
Fatemeh Heidarzadeh2
https://orcid.org/0000-0002-9209-2517
Ali Kheradmand3*
https://orcid.org/0000-0002-3704-9233

1Department of Psychiatry,Behavioral Neuroscience Research Center, Imam Hossein Hospital,Shahid Beheshti University of Medical Sciences, Tehran, Tehran Iran (the Islamic Republic of)
2Faculty of Medicine,Shahid Beheshti University of Medical Sciences, Tehran, Tehran Iran (the Islamic Republic of)
3Department of Psychiatry, Taleghani Hospital Research Development Committee,Shahid Beheshti University of Medical Sciences

Received: 16-12-2019 – Accepted: 03-11-2020

DOI: 10.1590/0101-60830000000274

ABSTRACT
The aim of this study was to investigate the relationship between narcissistic personality disorder (NPD) and mobile phone addiction
(MPA) among medical students. This analytical cross sectional study was conducted on medical interns and residents in 2018. Smartphone
addiction scale (SAS) was used to examine the MPA and Narcissistic Personality Inventory (NPI-16) questionnaire was used to investigate
the NPD. Also, demographic information including age, gender, residence, educational level and marital status were also recorded.160
medical students participated in this study. The prevalence of MPA and NPD were 38.1% and 30% respectively. The relationship between
MPA and marital status, residence and educational level were statistically significant (P<0.01). Among the demographic variables only
marital status has a significant relationship with NPD (P = 0.016). MPA was significantly higher among individuals with NPD (P <0.0001).
It is recommended that MPA be considered as a risk factor for NPD in future studies.

Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1):24-28

Keywords: Narcissistic personality disorder, Mobile phone, Addiction, Medical Students

Background technology and disturbances such as attention deficit hyperactivity

Over the years, the use of social and mobile networks has grown
with the aim of social activities, leisure and spending time between
people around the world1-3. Research results have shown that
the use of mobile phones has become an obligatory ritual of the
people's lives4. Results of study conducted in the United States on
over 2,000 people showed that 60% of people cannot even spend
an hour without their mobile phone, 54% were also checking their
mobile while lying in bed, 39% were using mobile phone in the
bathroom, 24% were using while driving, and 30% were checking
their mobile phone during a meal with others5. Although mobile
phone dependence quickly became a normal natural phenomenon,
concerns about addiction to these networks and mobile phones
have increased6,7. It seems that the high usage of the mobile phone
is associated with the large use of social networks, and social
networks create dependencies8. Results of studies have also shown
that people who use a lot of virtual networks or cyberspace are
also susceptible to mobile phone addiction (MPA)9. Extroverted
people tend to have more smart phones and are more interested
in using text messages to communicate10. While introverts use
mobile phones to compensate for their non-social relationships,
and are more likely to be addicted to mobile phones11- 13. Recently,
a significant relationship has been found between dependence to
disorder, obsessive compulsive disorder, anxiety and depression14-16.
Narcissism is a personality disorder that is associated with
grandiosity and feeling of being worthy17. Affected people have a
tendency to show an ideal of being to win others' praise18. These
people regularly use social networks such as Facebook to update
their personal information, put photos and try to attract others19-21.
It has recently been suggested that individuals with Narcissistic
personality disorder (NPD) are at increased risk for social
networking dependence (SND), and this dependence has many
adverse effects for them, including the feeling of dissatisfaction with
personal relationships and psychological stress. In line with these
studies, it has been shown that narcissism can lead people to SND
because they have a great tool for attracting others' attention19-21.
While previous studies failed to determine the relationship between
NPD and its predictive role in dependence to social networks,
recent studies have shown a positive relationship between NPD and
SND3,22,23. It is hypothesized that social networks provide an ideal
condition for narcissistic purposes and a better chance of displaying
to large number of spectators24.
The results of the studies have demonstrated that medical
students are more interested in taking photos of themselves,
which can indicate a more prevalent NPD in these individuals25.
Also in a study in India, the prevalence of MPA was more among

Address for correspondence: Ali Kheradmand, M.D, Associate professor of psychiatry, Taleghani Hospital Research Development Committee , Behavioral Sciences Research Center, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
25 Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1): 24-28
medical students26 However, there are insufficient studies about the
prevalence of this disorder among medical students.
Objective
Because the medical profession is critical and the fact that doctors
are directly linked to the people, it is necessary to obtain accurate
information on the common disorders among them in order to
provide solutions to improve these issues. The aim of this study
was to investigate the relationship between NPD and MPA among
medical students.
Methods
Study Design
This cross-sectional study was conducted in 2018 on interns and
resident physician in Shahid Beheshti University of Medical
Sciences, Tehran, Iran. According to Cochran formula, 160
samples were selected with simple random sampling method. In
this study, a consensus sampling’ technique was used. Sampling
continued until the ideal sample size was reached. The response
rate was (90.9%). Out of 176 medical students, 160 (90.9%) fully
answered the questions and entered the study. The inclusion criteria
were studying at medical internship or residency and having a
smartphone with the ability to communicate with cyberspace.
Individuals with a history of illness or psychiatric problems, and
the use of psychosocial drugs as well as those who did not consent
to participate in the study were excluded.
Measurements
In this study, a standard questionnaire named smartphone
addiction scale (SAS) was used to examine the MPA. The
Narcissistic Personality Inventory (NPI-16) questionnaire was used
to investigate the NPD. Also, demographic information including
age, gender, residence, educational level and marital status were
also recorded. All questionnaire were provided to participants and
they should complete them with pen/pencil.
The SAS questionnaire consists of 33 questions with Likert scale
including different aspects of the MPA and each question has a
score between 1 point (completely disagree) to 6 points (I totally
agree). Validity and reliability of this questionnaire have been
confirmed by Amirlatifi et al. in Iran27 and the score of 106 and
higher is considered as addiction to smart phone (Appendix A).
The NPI-16 questionnaire is a shortened version of 40-item
questionnaire of NPD that has been made by Ames et al. for
measuring the characteristics of narcissism28. This questionnaire
has no sub-scale and evaluates NPD based on a one-dimensional
approach. NPI-16 consists of two phrases with the opposite
concept that the respondent must select one of them. The test-retest
reliability coefficients reported 0.85 for 5 weeks28. Also, validity and
reliability of this questionnaire in Iranian society were confirmed
in Mohammadzadeh's study and Cronbach's alpha coefficient was
0.79. This study concluded that in the Iranian population, NPI-16 is
an appropriate tool for screening in NPD-related research29. In the
NPI-16 questionnaire there are two columns that each column has
16 questions. The questions of first column suggests the narcissism
and the opposite column suggests the lack of narcissism. Each
answer in the first column gives one point and each answer in the
other one is zero. A total of 8 points and higher are considered as
NPD (Appendix B)
Ethical Consideration
Signed informed consents were obtained from all participants.
The researchers were committed to the ethical guidelines of the
Declaration of Helsinki and approval for the study was obtained
from the Institutional Review Board at Shahid Beheshti University
of Medical Sciences30.
Statistical Analysis
Data were analyzed by Statistical Package for the Social Sciences
(SPSS) software version 16 (IBM, Chicago, IL, USA) using
independent t test and chi square tests. In all calculations, P value
of <0.05 was considered statistically significant in analytical tests.
Results
Out of 176 medical students, 160 (90.9%) fully answered the
questions and entered the study. Among them 79 (49.4%) were
female and 81 (50.6%) were male. The mean age of participants
was 26.96 ± 2.43 years. 112 (70%) were single and 48 (30%) were
married. Also, 90 (56.25%) were medical interns and 70 (43.75%)
were residents. 95 (59.4%) were living in the home and 65 (40.6%)
lived in the dormitory. The results of the SAS questionnaire showed
that in general, 61 (38.1%) students had scores higher than 106
who had MPA, and 48 (30%) students according to the NPI-16
questionnaire had a score above 8 that was considered to be NPD.
According to the Chi-square test, there was no significant
relationship between MPA and gender (P = 0.2). However, the
relationship between MPA and marital status (P <0.0001), residence
(P = 0.006) and educational level (P <0.0001) were statistically
significant. So that MPA in participants who lived in dormitory and
were single and intern were significantly higher (Table 1).
Also, the results of the Chi-square test showed that among the
demographic variables only marital status has a significant
relationship with NPD, so that NPD was significantly more
prevalent in singles (P = 0.016). However, there was no statistically
significant relationship between NPD and other parameters such
as gender (P = 0/5), residence (P = 0.129), and educational level
(P = 0/728) 2). Finally, according to the Chi-square test, MPA was
significantly higher among individuals with NPD (P <0.0001)
(Table 1 and 2).
To remove the effect of covariate and to see which variable account
for most of the variance, ANCOVA analysis was done. This analysis
showed the effect of the covariates was not statistically significant
and there was statistically association between MPA and NPI after
adjusting for other variables.
Discussion
In this study, the relationship between medical students' addiction
to mobile phones and NPD was investigated. In general, 38.1%
of students had MPA and 30% had NPD. In a review article31, the
prevalence of NPD in different societies was reported to be 2.6%, so
results of present study indicate that this disorder is more prevalent
among medical students. This can be justified by the fact that the
medical field has a high degree of respect in the community, and
a lot of people's attention to this discipline can lead students to
this disorder. Furthermore, the prevalence of MPA was reported
16% in general population of Switzerland32 and 23.3% in Chinese
students33.The results of the present study have shown higher
results in the medical students.
The results of this study showed that among demographic
factors only marital status was significantly related with NPD, while
the residence, educational level and gender had no relation to this
disorder. Similar to the results of present study, Stinson et al. reported
that NPD was more common in single individuals34. Despite to the
results of the present study, Grijalva et al. in 201535 and Khalili et al.
from Iran in 201717 demonstrated that the prevalence of NPD was
more in men than women respectively. Given this contradiction, it
 Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1): 24-28 26

Table 1: Relationship between mobile phone addiction and other study variables
Mobile phone addiction P value
Yes (n=61) No (n=99) (chi square test)
Gender
Male (n=81) 27 (44.3%) 54 0.2
(54.5%)
Female (n=79) 34 (55.7%) 45
(45.5%)
Marital Status
Married (n=48) 5 (8.2%) 43 <0.0001*
(43.4%)
Single (n=112) 56 (91.8%) 56
(56.6%)
Residence
Personal home (n=95) 28 (45.9%) 67 0.006*
(67.7%)
Dormitory (n=65) 33 (54.1%) 32
(32.3%)
Educational Level
Internship (n=90) 46 (75.4%) 44 <0.0001*
(44.4%)
Residency (n=70) 15 (24.6%) 55
(55.6%)
Narcissistic personality disorder
Yes (n=48) 29 (47.5%) 19 <0.0001*
(19.2%)
No (n=112) 32 (52.5%) 80
(80.8%)

Table 2: Relationship between Narcissistic personality disorder and other study variables
Narcissistic personality P value
disorder (chi square test)
Yes No
(n=48) (n=112)
Gender
Male (n=81) 26 (54.2%) 55 (49.1%)
0.5
Female (n=79) 22 (45.8%) 57 (50.1%)
Marital Status
Married (n=48) 8 (16.7%) 40 (35.7%)
0.016*
Single (n=112) 40 (83.3%) 72 (64.3%)
Residence
Personal home (n=95) 25 (52.1%) 70 (62.5%)
0.219
Dormitory (n=65) 23 (54.1%) 42 (37.5%)
Educational Level
Internship (n=90) 20 (41.7%) 50 (44.6%)
0.728
Residency (n=70) 28 (58.3%) 62 (55.4%)
Mobile Phone Addiction
Yes (n=48) 29 (47.5%) 19 (19.2%)
<0.0001*
No (n=112) 32 (52.5%) 80 (80.8%)
27 Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1): 24-28
seems that gender in different populations has different relationship
with NPD. Also, the results of this study demonstrated that other
demographic factors have significant relationship with MPA. The
results of this study were similar to the results of study conducted
by Wang et al.33. The increased prevalence of MPA among residents
of the dormitory could be due to lack of facilities in dormitories and
the separation of people from the family using mobile phones and
social networks to fill their vacancies. Also, medical residents spent
less time in using their mobile phone due to less free time33, which
can justify the results obtained in the study.
Finally, the results of this study showed that MPA is significantly
higher among students with NPD. According to ANCOVA analysis
the effect of the covariates was not statistically significant and there
was statistically association between MPA and NPI after adjusting
for other variables. Similar to the results of this study, Pearson et al.
demonstrated that not only individuals with NPD had more MPA,
but that addiction to the mobile phone has led people to narcissistic
traits, even in those with no personality disorder3. Currently, smart
phones play an important role in people's lives due to their easy
access to the Internet. People can use it to play, communicate with
others, store and share information, access scientific resources. It is
also more common in younger people because of early technology
learning37. In a study conducted by Anderson and colleagues,
there was a significant relationship between social networking and
NPD22. Also, the results of studies show that individuals with NPD
tend to have more attractive images on social networks24,38. Since
the use of mobile phones is more in access to these networks, it can
be argued that there is a significant relationship between addiction
to mobile phone and NPD, which is also proven in present study.
Also, the abundant use of mobile phones can have important effects
on mental health including depression and chronic anxiety39,40.
It can also increase suicide among people41. This study does not
address the consequences of using mobile phones. But despite to
the results of present study, Hussain et al. reported that there is not
a significant relationship between MPA and NPD among general
population. This difference in results may be due to the different
study population42.
Of course, there is the hypothesis that MPA can create narcissistic
characteristics. In this study, the relationship between these two
parameters has been investigated, but one of the limitations of this
study was the lack of the longitudinal relationship between NPD
and MPA and the absence of a control group. In future studies, it
is recommended that MPA be considered as a risk factor for NPD
compared with control group.
Another limitation of this study was common method bias
since the data was collected using a single instrument at a discrete
point in time.
Due to the importance of personality disorders, especially
narcissism and its close relationship with MPA, it is recommended
that these disorders be considered when students enter universities,
so that they can be addressed by counseling and psychotherapy
sessions if necessary. It is also better to consider MPA as a risk factor
for narcissism if students are suspected of having this disorder.
Conclusion
The results of this study demonstrated that the prevalence of MPA
was 38.1% and the prevalence of NPD was 30% among medical
students. MPA was significantly higher in students with lower
education level, singles and dormitory residents while NPD was
higher in singles. It was also found that MPA was significantly
higher in individuals with NPD. It is recommended that MPA be
considered as a risk factor for NPD in future studies.
Acknowledgments: The authors would like to thank all the study
participants.
Authors’ Contribution: All authors had equal role in design, work,
statistical analysis and manuscript writing.
Conflict of Interest: The authors declare no conflict of interest.
References
1. Kuss DJ, Griffiths MD. Online social networking and addiction—a review
of the psychological literature. International journal of environmental
research and public health. 2011;8(9):3528-52.
2. Allen KA, Ryan T, Gray DL, McInerney DM, Waters L. Social media
use and social connectedness in adolescents: The positives and the
potential pitfalls. The Educational and Developmental Psychologist.
2014;31(1):18-31.
3. Ryan T, Xenos S. Who uses Facebook? An investigation into the
relationship between the Big Five, shyness, narcissism, loneliness, and
Facebook usage. Computers in human behavior. 2011;27(5):1658-64.
4. Campbell SW, Park YJ. Social implications of mobile telephony: The rise
of personal communication society. Sociology Compass. 2008;2(2):371-
87.
5. Lookout Mobile Security. Mobile Mindset Study. June 2012. [Available
from: Retrieved from https://www.mylookout.com/resources/reports/
mobile-mindset (July 20, 2016).
6. Boyd DM, Ellison NB. Social network sites: Definition, history,
and scholarship. Journal of computer‐mediated Communication.
2007;13(1):210-30.
7. Andreassen CS, Griffiths MD, Gjertsen SR, Krossbakken E, Kvam
S, Pallesen S. The relationships between behavioral addictions and
the five-factor model of personality. Journal of behavioral addictions.
2013;2(2):90-9.
8. Salehan M, Negahban A. Social networking on smartphones: When
mobile phones become addictive. Computers in Human Behavior.
2013;29(6):2632-9.
9. Wu AM, Cheung VI, Ku L, Hung EP. Psychological risk factors of
addiction to social networking sites among Chinese smartphone users.
Journal of behavioral addictions. 2013;2(3):160-6
10. Bianchi A, Phillips JG. Psychological predictors of problem mobile
phone use. CyberPsychology & Behavior. 2005;8(1):39-51
11. Ross C, Orr ES, Sisic M, Arseneault JM, Simmering MG, Orr RR.
Personality and motivations associated with Facebook use. Computers
in human behavior. 2009;25(2):578-86.
12. Amichai-Hamburger Y, Vinitzky G. Social network use and personality.
Computers in human behavior. 2010;26(6):1289-95.
13. Roberts JA, Pullig C, Manolis C. I need my smartphone: A hierarchical
model of personality and cell-phone addiction. Personality and
Individual Differences. 2015;79:13-9.
14. Allam MF. Excessive internet use and depression: Cause-effect bias?
Psychopathology. 2010;43(5):334.
15. Cheever NA, Rosen LD, Carrier LM, Chavez A. Out of sight is not out
of mind: The impact of restricting wireless mobile device use on anxiety
levels among low, moderate and high users. Computers in Human
Behavior. 2014;37:290-7.
16. Enez Darcin A, Kose S, Noyan CO, Nurmedov S, Yılmaz O, Dilbaz
N. Smartphone addiction and its relationship with social anxiety and
loneliness. Behaviour & Information Technology. 2016;35(7):520-5.
17. Khalili N, Vaziri-Harami R, Jahani Y. Construction and Validation of the
Narcissism and Vulnerable Narcissism Scale in a Non-clinical Sample in
Iran. Afzalipour J Clin Res 2017; 2(1-2): 23-37.
18. Sherry SB, Gralnick TM, Hewitt PL, Sherry DL, Flett GL. Perfectionism
and narcissism: Testing unique relationships and gender differences.
Personality and Individual Differences. 2014;61:52-6.
19. Carpenter CJ. Narcissism on Facebook: Self-promotional and anti-social
behavior. Personality and individual differences. 2012;52(4):482-6.
20. Mehdizadeh S. Self-presentation 2.0: Narcissism and self-esteem
on Facebook. Cyberpsychology, behavior, and social networking.
2010;13(4):357-64.
21. Davenport SW, Bergman SM, Bergman JZ, Fearrington ME. Twitter
versus Facebook: Exploring the role of narcissism in the motives
and usage of different social media platforms. Computers in Human
Behavior. 2014;32:212-20
 Vaziri-Harami R / Arch Clin Psychiatry. 2021;48(1): 24-28
22. Andreassen CS, Pallesen S, Griffiths MD. The relationship between
addictive use of social media, narcissism, and self-esteem: Findings from
a large national survey. Addictive Behaviors. 2017;64:287-93.
23. Hsu C-W. Staging on the Internet: Research on online photo album users
in Taiwan with the spectacle/performance paradigm. Cyberpsychology
& Behavior. 2007;10(4):596-600
24. Buffardi LE, Campbell WK. Narcissism and social networking web sites.
Personality and social psychology bulletin. 2008;34(10):1303-14
25. Dutta E, Sharma P, Shah N, Bharati A, Sonavane S, Desousa A. Attitude
toward selfie taking and its relation to body image and narcissism
in medical students. Indian journal of psychological medicine.
2018;40(1):17.
26. Dixit S, Shukla H, Bhagwat A, Bindal A, Goyal A, Zaidi AK, et al. A
study to evaluate mobile phone dependence among students of a
medical college and associated hospital of central India. Indian journal
of community medicine: official publication of Indian Association of
Preventive & Social Medicine. 2010;35(2):339.
27. Amirlatifi ES, Kheradmand A, Mazaheri A, Sohrabi MR. Frequency
of smart phone dependence among students in Tehran, 2017 and its
relationship with personality traits. Psychiatrist degree thesis. Shahid
Beheshti University of Medical Sciences, 2017; 203.
28. Ames DR, Rose P, Anderson, CP. The NPI-16 as a short measure of
narcissism. J Res Pers 2006; 40: 440-50.
29. Mohammadzadeh A.Iranian validation of the narcissistic personality
inventory-16. Journal of Fundamentals of Mental Health 2010; 11(4):
274-81.
30. Abbasi M, Nabavi SM, Fereshtehnejad SM, Ansari I, Zerafatjou N,
Shayegannejad V, Mohammadianinejad SE, Farhoudi M, Noorian A,
Razazian N, Abedini M, Faraji F. Risk factors of Multiple sclerosis and
their Relation with Disease Severity: A Cross-sectional Study from Iran.
Arch Iran Med. 2016; 19(12): 852 – 860.
31. Dhawan N, Kunik ME, Oldham J, Coverdale J. Prevalence and treatment
of narcissistic personality disorder in the community: a systematic
review. Comprehensive psychiatry. 2010;51(4):333-9
32. Haug S, Castro RP, Kwon M, Filler A, Kowatsch T, Schaub MP.
Smartphone use and smartphone addiction among young people in
Switzerland. Journal of behavioral addictions. 2015;4(4):299-307
28
33. Wang C, Wang S, Li W, Dong X, Chi G. Study on the mobile phone
dependence syndrome and its distribution among 2213 college
students in Guangzhou. Zhonghua Liu Xing Bing Xue Za Zhi. 2013
Oct;34(10):949-52.
34. Stinson FS, Dawson DA, Goldstein RB, Chou SP, Huang B, Smith
SM, et al. Prevalence, correlates, disability, and comorbidity of DSM-
IV narcissistic personality disorder: results from the wave 2 national
epidemiologic survey on alcohol and related conditions. J Clin
Psychiatry. 2008 Jul;69(7):1033-45.
35. Grijalva E, Newman DA, Tay L, Donnellan MB, Harms PD, Robins
RW, et al. Gender differences in narcissism: A meta-analytic review.
Psychological bulletin. 2015;141(2):261
36. Pearson C, Hussain Z. Smartphone Use, Addiction, Narcissism, and
Personality: A Mixed Methods Investigation. International Journal of
Cyber Behavior, Psychology and Learning 2015;5(1):17-32.
37. Kuss DJ, Griffiths MD. Social networking sites and addiction: Ten
lessons learned. International Journal of Environmental Research and
Public Health. 2017;14(3):311
38. Wang JL, Jackson LA, Zhang DJ, Su ZQ. The relationships among the Big
Five Personality factors, self-esteem, narcissism, and sensation-seeking
to Chinese University students’ uses of social networking sites (SNSs).
Computers in Human Behavior. 2012;28(6):2313-9
39. Lepp A, Barkley JE, Karpinski AC. The relationship between cell phone
use, academic performance, anxiety, and satisfaction with life in college
students. Computers in Human Behavior. 2014;31:343-50.
40. Augner C, Hacker GW. Associations between problematic mobile phone
use and psychological parameters in young adults. International journal
of public health. 2012;57(2):437-41.
41. Katsumata Y, Matsumoto T, Kitani M, Takeshima T. Electronic media
use and suicidal ideation in Japanese adolescents. Psychiatry and clinical
neurosciences. 2008;62(6):744-6.
42. Hussain Z, Griffiths MD, Sheffield D. An investigation into problematic
smartphone use: The role of narcissism, anxiety, and personality factors.
Journal of behavioral addictions. 2017;6(3):378-86..
 Original article

Personality, cognitive emotion regulation and insomnia

Ana Paula Amaral1,2*
https://orcid.org/0000-0003-0760-4416
Sandra Carvalho Bos2
https://orcid.org/0000-0002-8077-6196
Maria João Soares2
https://orcid.org/0000-0002-7856-280X
Ana Telma Pereira2
https://orcid.org/0000-0001-9980-441X
Mariana Marques2,3
https://orcid.org/0000-0002-4674-1045
Nuno Madeira2,3
https://orcid.org/0000-0001-5009-8841
Vasco Nogueira2,3
https://orcid.org/0000-0002-2911-8227
Miguel Bajouco2,3
https://orcid.org/0000-0003-3531-1135
António Macedo2,3
https://orcid.org/0000-0003-2180-2718

Coimbra Health School, Polytechnic Institute of Coimbra, Coimbra, Portugal

1

Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

2

Department of Psychiatry, Coimbra University Hospital Center, Coimbra, Portugal

3

Institution where the study was conducted

University of Coimbra, Faculty of Medicine, Institute of Medical Psychology, Pólo I, Edifício Faculdade Medicina, Rua Larga, 3004-504, Coimbra, Portugal

Received: 23-12-2019 – Accepted: 03-11-2020

DOI: 10.1590/0101-60830000000275

Amaral AP / Arch Clin Psychiatry. 2021;48(1):29-35

Introduction Repetitive thinking in the evening is associated with longer sleep

Insomnia is experienced by approximately 19% of university
students1 and is associated with fatigue, depression, anxiety, stress,
lower levels of quality of life2 and lower academic performance3.
Specific personality traits are observed in insomniacs4. Individuals
with high scores of neuroticism, i.e., who consider themselves
nervous or anxious, report poorer sleep quality5 and the ones with
high perfectionism also reveal more insomnia severity6. Doubts
about actions and concerns about mistakes are perfectionism
dimensions positively associated with insomnia7. Socially
prescribed perfectionism, i.e. the perception that others hold very
high expectations on oneself, is another perfectionism dimension
which can predict difficulties initiating and/or maintaining sleep
in the long term8. In addition, increased perception of stress may
also predispose the individual to experience emotional distress and
insomnia9.
Neuroticism, perfectionism, increased stress reactivity and
maladaptive emotional regulation strategies can act as precursors
of cognitive hyperarousal which in turn can contribute to sleep
difficulties9. Insomniacs might also share a genetic and physiological
vulnerability to hyperarousal10 which could be intensified by
cognitive activity.
Individuals with perseverative negative thinking style, i.e.,
think about one´s problems (current, past or future) or negative
experiences (past or anticipated) in a repetitive, intrusive and
persistent way11 are also more likely to report sleep difficulties12.
latency, less sleep efficiency and shorter total sleep time, sleep
parameters objectively measured with actigraphy13 .
Cognitive strategies can help managing, regulating and
controlling emotions and feelings in perceived distressed
situations14. Self-blame, blaming others, rumination or focus
on thought and catastrophizing are strategies considered to be
less adaptive and associated with depression and anxiety while
accepting, refocus on planning, positive refocusing, positive
reappraisal and putting into perspective are more adaptive and
associated with less depression and anxiety14. Difficulties regulating
emotions when upset are associated with insomnia severity15 and
rumination, defined as thinking about feelings and thoughts related
to a negative event that occurred in the past14, is associated with
poor sleep16.
A bi-directional effect between sleep and mood is expected.
Poor sleep quality is associated with subsequent lower positive
affect and higher negative affect during the day17 whereas perceived
stress can predict decreased sleep quality18.
The role of personality factors, stress reactivity and emotion
regulation processes for insomnia onset or maintenance requires
further investigation to substantiate its evidence. The aim of the
present study was to explore the association between personality
traits (neuroticism and perfectionism), stress reactivity and
cognitive emotional regulation processes and insomnia in a sample
of university students, controlling the effect of negative affect,
which is likely to influence this association.

Address for correspondence: Ana Paula Amaral, Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal, Email: amaral.anapm@gmail.com
30 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35
Methods
Participants and Procedures
The research project was approved by the Ethical Committee
of the Faculty of Medicine, University of Coimbra, Portugal.
The Portuguese validated versions of a set of self-reported
questionnaires were administered to a convenience community
sample of 549 students (80.1% females) from the first to the sixth
year of different courses (Medicine, Dentistry, Psychology, Social
Service and Health Technologies) from University of Coimbra and
from other higher educational schools in the cities of Coimbra and
Oporto (further details are described in a previous study12). Aims of
the investigation were explained to faculty professors, who agreed
to collaborate. At class sessions, after a brief description of the
study and ensuring confidentiality, informed written consent was
obtained from students who agreed to participate in the research.
Mean age of participants was 20.5 years (± 4.83) and was not
significantly different between genders (p= .154). The majority of
students was single (96.4%) and Portuguese (88.5%).
Instruments
Eysenck Personality Inventory (EPI19)
A short version of the Eysenck Personality Inventory (EPI)20 was
used to measure neuroticism and extraversion (6 items for each
personality dimension). Responses are given on a 4-point Likert
scale ranging from almost never (1) to almost always (4). Higher
values indicated higher levels of neuroticism and extraversion20,21.
The Portuguese short version of EPI was used21 in our study and
reasonable internal consistencies were obtained neuroticism,
Cronbach Alpha, α=.61; extraversion, α=.66.
Multidimensional Perfectionism Scale (MPS22).
The Multidimensional Perfectionism Scale (MPS22) is a 35 item
self-reported instrument which evaluates perfectionism levels.
Responses are given on a five-point Likert scale ranging from
strongly disagree (score 1) to strongly agree (score 5). Higher
scores indicate higher levels of perfectionism. The scale includes 6
perfectionism dimensions: personal standards (PS), concern over
mistakes (CM), doubts about actions (DA), parental expectations
(PE), parental criticism (PC) and organization (O). The Portuguese
version of MPS has shown good psychometric properties with
internal consistencies of perfectionism dimensions varying
between α=.74 to α=.93 and a value of α=.86 for the MPS total23.
In our study a shorter MPS version was used with 24 items (4 items
with the highest loadings within each perfectionism dimension of
the Portuguese version of MPS were selected)23.
Multidimensional Perfectionism Scale (MPS24)
The Multidimensional Perfectionism Scale (MPS) by Hewitt and
Flett24 is a self-reported questionnaire with 45 items which assesses
3 dimensions of perfectionism: self-oriented perfectionism, socially
prescribed perfectionism and other-oriented perfectionism.
Responses to each item are given on a seven-point Likert scale
ranging from strongly disagree (score 1) to strongly agree (score
7). Higher scores are associated with higher levels of perfectionism.
The Portuguese version of the original MPS has shown very good
psychometric properties25. In our study only dimensions related to
self-oriented perfectionism and socially prescribed perfectionism
were investigated (32 items) as in previous studies these specific
perfectionism dimensions were particularly associated with sleep
difficulties8. In our study an internal consistency of α= .85 was
observed for self-oriented perfectionism and α= .79 for socially
prescribed perfectionism.
Perceived Stress Scale (PSS26)
The Preceived Stress Scale (PSS26), a 10 item self-reported
questionnaire, was used to measure perceived stress. Responses are
given on a 5 point likert scale ranging from 0 “never” to 4 “very
often”. An higher score is associated with more severe perceived
stress. The PSS Portuguese version27 includes two factors and has
reveal good psychometric properties (total scale, α=.87): 1) Factor
1 “perceived distress” related to the perception of how life events
can be stressful (unpredictable, uncontrollable, overloading) and
can have an emotional impact (α=.84) and 2); Factor 2 “perceived
coping” implies lack of control over stressful life events and doubts
about one´s coping abilities with problems (α= .75).
Perseverative Thinking Questionnaire (PTQ11).
The Perseverative Thinking Questionnaire (PTQ) is a 15 item
content-independent self-report questionnaire that assesses the
core characteristics of perseverative negative thinking11. Reponses
are given on a 5-point Likert scale ranging from 0 “never” to 4
“almost always”. Higher scores indicate more severe perseverative
negative thinking11. The preliminary version of the Portuguese
PTQ-1528 revealed two factors: 1) repetitive thought (represents
the actual thinking process) and 2) cognitive interference and
unproductiveness (refers to individuals’ perceived dysfunctional
effects). Its factorial structure does not overlap with the original,
yet it is meaningful. Reliability analyses revealed high internal
consistencies for both factors (α=.86 and α=.87, respectively) as
well as for the total scale (α=.93)28.
Cognitive Emotion Regulation Questionnaire (CERQ29)
The Cognitive Emotion Regulation Questionnaire (CERQ) is a
36-item multidimensional questionnaire designed to measure
specific cognitive emotion regulation strategies used in response to
threatening or stressful life events29. Responses are given on a 5-point
Likert scale ranging from 1 “almost never” to 5 “almost always” 29.
The Portuguese validated version30 evaluates 8 conceptually distinct
dimensions, overlaps with the original factor structure and reveals
good psychometric properties: positive reappraisal/planning,
α=.89; positive refocusing, α=.86; rumination, α=.78; blaming
others, α=.79; putting into perspective, α=.80; self-blame, α=.76;
acceptance, α=.70; catastrophizing, α=.74; total α=.89.
Profile of Mood States (POMS31)
The Profile of Mood States (POMS) is a 65 item scale that assesses
feelings and emotions that people commonly experience31.
Responses are given on a 5 point Likert scale, oscillating from 0
“not at all” to 4 “extremely”, and refer to the previous month. Five
dimensions of the scale were explores: tension-anxiety; depression-
dejection; anger-hostility; vigor-activity and fatigue-inertia. The
Portuguese version of POMS32 has shown good psychometric
properties in our study: tension-anxiety, α= .87; depression-
dejection, α= .93; anger-hostility, α= .92; vigor-activity, α= .82;
fatigue-inertia, α= .85. and negative affect, α= .96. An additional
dimension of negative affect (NA) was considered in the present
study by adding scores of three subscales: tension-anxiety,
depression-dejection and anger-hostility (α= .96).
Insomnia Inventory33
An Insomnia Inventory was used to identify cases of insomnia. The
first items assessed whether the student experienced difficulties
initiating or maintaining sleep or early awakening in the previous
month. If the sleep complaint was present it was explored whether
it was associated with non-restorative sleep or poor sleep quality.
 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35
Additionally, it was assessed if the sleep complaint was associated
with daytime impairment and if the sleep difficulty occurred even
when adequate opportunity and circumstances for sleep existed.
Sleep groups were formed: Insomnia group included students who
experienced a persistent sleep complaint associated with non-
restorative sleep or perception of poor or very poor sleep in the
previous month, associated with complaints of daytime impairment
despite adequate opportunity and circumstances to sleep; Insomnia
symptoms group integrated students with a sleep difficulty and non-
restorative sleep or poor/very poor sleep quality, without daytime
impairment; Good sleepers group involved students without sleep
complaints and who experienced restorative sleep or reasonable,
good or very good sleep quality.
Statistical Analyses
Descriptive analyses were conducted to investigate the frequency
of sleep complaints and the prevalence of insomnia. Additionally,
ANOVA tests and Post hoc tests were applied to investigate
differences between sleep groups relatively to psychological
variables. The Tukey HSD post hoc test was applied when equal
variances between groups were assumed and Tamhane`s post hoc
test was used when equal variances were not assumed.
Results
Descriptive Data
Insomnia was observed in 15.1% of the total sample, 17.1% in
females and 6.7% in males. Considering the type of sleep complaint
it was observed that 30.9% of the total sample mentioned early
morning waking, 29.8% reported difficulties initiating sleep and
27.9% referred difficulties maintaining sleep. Early morning
waking was more often reported by women than men (33.2% versus
21.5%) as well as difficulties initiating sleep (31.3% versus 23.6%)
and difficulties maintaining sleep (30.3% versus 17.8%).
Differences between sleep groups relatively to
psychological factors (Table 1)
In comparison with the group of good sleepers, insomnia
symptoms group and the insomnia group reported higher levels
of neuroticism, concerns over mistakes. doubts about actions,
parental expectations, parental criticism, higher levels of socially
prescribed perfectionism and perceived stress (total score and sub-
scales scores), more perseverative thinking (total score), higher
values of repetitive thinking and perceived cognitive interference/
unproductiveness, higher levels of rumination, self-blame,
catastrophizing and higher values of tension-anxiety, depression-
dejection, anger-hostility, fatigue-inertia and lower values of
vigour-activity.
Additionally, it was observed that the insomnia group reported
lower values of extraversion (M=15.2±2.85), lower scores on
positive refocus (M=12.6±4.66) and higher levels of acceptance
(M=12.4±3.27) in comparison with the group of good sleepers
(M=16.1±2.62, p=.033; M=14.2 ± 3.79, p=.014; M=11.2±3.09,
p=.028, respectively).
Significant differences were not observed between sleep groups
relatively to particular dimensions of perfectionism, i.e., personal
standards, organization, self-oriented perfectionism or specific
cognitive emotional regulation processes, i.e., positive reappraisal/
planning, blaming others and putting in perspective. Significant
differences were equally not observed between sleep groups
relatively to the total score of the Cognitive Emotional Regulation
Questionnaire.
31
Differences between sleep groups in psychological factors
controlling for negative affect
To investigate whether the results observed previously were a result
of high values of psychological distress, an additional variable,
designated by negative affect, was formed by adding the scores of
three POMS dimensions: tension-anxiety, depression-dejection
and anger-hostility. Individuals with values above percentile 75
(score of 50) in the negative affect variable were not included in the
subsequent analyses (Table 2).
In comparison with the group of good sleepers, insomnia
symptoms group and the insomnia group reported higher values
of perceived stress scale (total score and sub-scores), more
perseverative thinking (total score) and repetitive thought, less
vigour-activity and more fatigue-inertia. The insomnia group
also revealed higher values of neuroticism, socially-prescribed
perfectionism and rumination in comparison with the group of
good sleepers.
Additionally, insomnia symptoms group reported more
concern over mistakes, doubts about actions, parental expectations
and parental criticism when compared with the group of good
sleepers.
Significant differences between sleep groups were not observed
in specific dimensions of perfectionism, i.e., personal standards,
organization, self-oriented perfectionism or in most cognitive
emotional regulation processes evaluated (except rumination).
Discussion
A consistent finding of our study was that students with insomnia
reported higher values of socially prescribed perfectionism in
comparison with good sleepers. This result is in line with previous
findings8. An additional contribution is that socially prescribed
perfectionism is still higher in insomniacs even when the effect of
negative affect is controlled for. This is a new finding and indicates
that socially prescribed perfectionism is a personality dimension
that should be worth considering in future longitudinal studies
when evaluating risk or predisposition factors for insomnia.
Higher scores on perfectionism dimensions related to concern
over mistakes, doubts about actions, parental expectations or
criticism were also observed in the insomnia group in comparison
with the group of good sleepers. When the effect of negative affect
was controlled for these differences were no longer observable.
Thus, negative affect possibly acts as a mediator enhancing the
effect of specific perfectionism dimensions on insomnia. Brand et
al.6 also observed that perfectionism was associated with insomnia
severity. When the effect of stress and emotion regulation processes
was considered, the association decreased considerably. Schmidt et
al.7 observed that perfectionism dimensions related to doubts about
actions and concerns about mistakes were positively associated with
insomnia severity while counterfactual thoughts (regret, shame and
guilt) mediated this effect.
Another consistent finding was that higher levels of neuroticism
were observed in individuals with insomnia or insomnia symptoms,
even when the effect of negative affect was controlled. This result is
in agreement with the literature5 and with the view that insomniacs
are individuals with a marked neuroticism trait4. In fact, individuals
with a specific psychological profile of high levels of neuroticism,
rumination, tendency to suppress negative emotions and less
capacity to cope are more likely to experience long term chronic
insomnia34.
As expected, the insomnia group perceived their lifes as
more stressful, doubting about their abilities to cope with
32 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35

Table 1: Comparisons between sleep groups relatively to personality traits, cognitive emotion regulation processes and mood
Good Insomnia Insomnia ANOVA Post-hoc
Sleepers Symptoms Group [3] Tests [*]
Group [1] Group [2]
EPI M (SD) M (SD) M (SD) p
Neuroticism 10.3 (2.10) 11.1 (2.46) 12.6 (2.19) <.001 1<2,3; 2<3
Extraversion 16.1 (2.62) 15.6 (2.72) 15.2 (2.85) .033 1>3
MPS (Frost et al., 1990))
Concern over mistakes 8.3 (2.65) 9.3 (3.03) 9.9 (3.32) <.001 1<2,3
Personal standards 11.7 (3.09) 12.0 (2.99) 12.1 (3.48) .388 -
Doubts about actions 9.3 (3.05) 10.4 (3.36) 11.4 (3.32) <.001 1<2,3; 2<3
Parental expectations 9.3 (3.57) 10.4 (3.41) 10.9 (4.33) .001 1<2,3
Parental criticism 6.5 (2.69) 7.3 (3.17) 8.4 (4.36) <.001 1<2,3
Organization 15.1 (3.27) 15.2 (3.11) 15.2 (4.08) .905 -
MPS (Hewitt and Flett, 1991))
Self-oriented perfectionism 76.4 (15.48) 77.6 (15.0) 76.8 (16.47) .730 -
Socially prescribed perfectionism 45.0 (9.83) 48.7 (9.80) 52.7 (11.34) <.001 1<2,3; 2<3
PSS
Total 17.1 (5.35) 21.0 (5.98) 24.3 (5.55) <.001 1<2,3; 2<3
F1: Perceived stress 10.4 (3.69) 13.2 (4.41) 15.3 (3.79) <.001 1<2,3; 2<3
F2: Perceived coping 6.7 (2.34) 7.7 (2.37) 9.0 (2.48) <.001 1<2,3; 2<3
PTQ
Total 23.6 (8.31) 27.1 (9.20) 30.0 (9.27) <.001 1<2,3; 2<3
F1: Repetitive Thought 13.0 (4.32) 14.8 (4.74) 16.2 (4.85) <.001 1<2,3
F2: Cognitive Interference 10.7 (4.68) 12.2 (5.23) 13.8 (5.09) <.001 1<2,3; 2<3
CERQ
Total 93.9 (16.0) 96.5 (16.77) 98.5 (17.66) .163 -
F1: Positive reappraisal/planning 23.5 (5.50) 23.0 (5.76) 22.1 (5.37) .212 -
F2: Positive refocusing 14.2 (3.79) 14.1 (4.18) 12.6 (4.66) .014 1,2>3
F3: Rumination 13 (3.49) 14.4 (3.87) 16.2 (4.31) <.001 1<2,3; 2<3
F4: Blaming others 6.7 (2.26) 7.2 (2.93) 7.4 (2.84) .109 -
F5: Putting into perspective 12.8 (3.53) 12.5 (3.35) 12.4 (3.96) .529 -
F6: Self-blame 5.6 (1.95) 6.2 (2.45) 6.8 (2.46) <.001 1<2,3
F7: Acceptance 11.2 (3.09) 11.4 (2.82) 12.4 (3.27) .028 1<3
F8: Catastrophizing 7.1 (2.28) 8.3 (3.06) 9.3 (3.83) <.001 1<2,3
POMS
Tension-Anxiety 10.7 (5.05) 15.9 (7.13) 18.3 (6.35) <.001 1<2,3; 2<3
Depression-Dejection 8.5 (6.90) 14.3 (11.26) 20.4 (11.80) <.001 1<2,3; 2<3
Anger-Hostility 7.4 (5.94) 11.7 (8.79) 15.9 (9.64) <.001 1<2,3; 2<3
Vigour-Activity 17.5 (4.42) 15.7 (5.41) 13.8 (5.45) <.001 1>2,3; 2>3
Fatigue-Inertia 7.4 (4.38) 10.4 (5.69) 12.7 (5.77) <.001 1<2,3; 2<3
Negative Affect 26.3 (16.17) 40.7 (24.89) 54.7 (25.33) <.001 1<2,3; 2<3
[*] Tukey HSD test or Tamhane test, as appropriate; PSS: Perceived Stress Scale, EPI: Eysenck Personality Inventory; MPS:
Multidimensional Perfectionism Scale; PTQ: Perseverative Thinking Questionnaire; CERQ: Cognitive Emotion Regulation
Questionnaire; POMS: Profile of mood states.
 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35 33

Table 2: Comparisons between sleep groups relatively to personality traits, cognitive emotion regulation processes and mood, controlling for
negative affect
Good Insomnia Insomnia ANOVA Post-hoc
Sleepers Symptoms Group [3] Tests [*]
Group [1] Group [2]
EPI M (SD) M (SD) M (SD) p
Neuroticism 10.0 (1.98) 10.4 (1.99) 12.3 (1.81) <.001 1,2<3
Extraversion 16.2 (2.58) 15.8 (2.60) 16.1 (2.51) .317 -
MPS (Frost et al., 1990))
Concern over mistakes 8.0 (2.36) 8.9 (2.81) 8.5 (2.38) .005 1<2
Personal standards 11.7 (3.11) 11.8 (2.71) 12.1 (3.18) .728 -
Doubts about actions 8.9 (2.83) 9.7 (3.10) 10.2 (2.68) .017 1<2
Parental expectations 9.1 (3.48) 10.2 (3.37) 10.6 (4.46) .007 1<2
Parental criticism 6.1 (2.21) 7.0 (2.98) 7.4 (3.60) .002 1<2
Organization 15.0 (3.30) 14.8 (3.22) 15.7 (3.82) .285 -
MPS (Hewitt and Flett, 1991))
Self-oriented perfectionism 77.0 (15.51) 76.3 (14.14) 74.3 (13.70) .620 -
Socially prescribed perfectionism 44.1 (9.79) 46.7 (9.89) 49.1 (9.61) .007 1<3
PSS
Total 16.2 (4.95) 19.1 (5.17) 21.4 (4.33) <.001 1<2,3; 2<3
F1: Perceived stress 9.7 (3.44) 11.8 (3.91) 13.3 (3.12) <.001 1<2,3
F2: Perceived coping 6.4 (2.28) 7.3 (2.18) 8.1 (2.26) <.001 1<2,3
PTQ
Total 22.7 (7.89) 24.9 (8.42) 28.8 (8.51) <.001 1<2,3; 2<3
F1: Repetitive Thought 12.5 (4.25) 13.9 (4.57) 16.0 (4.56) .001 1<2,3; 2<3
F2: Cognitive Interference 10.1 (4.35) 11.0 (4.60) 12.8 (4.59) .003 1<3
CERQ
Total 94.3 (16.20) 93.9 (16.95) 99.1 (18.36) .291 -
F1: Positive reappraisal/planning 24.0 (5.61) 23.2 (5.55) 23.6 (4.98) .436 -
F2: Positive refocusing 14.5 (3.78) 14.0 (4.43) 14.0 (5.00) .644 -
F3: Rumination 12.8 (3.52) 13.7 (3.74) 15.1 (4.32) .004 1<3
F4: Blaming others 6.6 (2.09) 6.76 (2.98) 7.5 (3.00) .165 -
F5: Putting into perspective 13.2 (3.54) 12.5 (3.51) 13.0 (3.88) .332 -
F6: Self-blame 5.4 (1.84) 5.8 (2.12) 5.9 (1.41) .227 -
F7: Acceptance 11.2 (3.19) 11.1 (2.96) 12.3 (3.55) .192 -
F8: Catastrophizing 7.0 (2.26) 7.5 (2.67) 8.1 (3.57) .051 -
POMS
Vigour-Activity 17.9 (4.33) 16.3 (5.45) 15.4 (5.13) <.001 1>2,3
Fatigue-Inertia 6.7 (3.93) 8.0 (4.46) 9.0 (4.10) <.001 1<2,3
[*] Tukey HSD test or Tamhane test, as appropriate; PSS: Perceived Stress Scale, EPI: Eysenck Personality Inventory; MPS: Multidimensional
Perfectionism Scale; PTQ: Perseverative Thinking Questionnaire; CERQ: Cognitive Emotion Regulation Questionnaire; POMS: Profile of mood
states

stress12 and revealed higher levels of perseverative thinking,
particularly repetitive thinking and cognitive interference or
unproductiveness13. In the literature, repetitive thought in the
evening has been associated with longer sleep onset latency and
lower sleep efficiency13. The novelty of our study is that levels of
perceived stress and perseverative thinking were still higher in the
insomnia group when the effect of negative affect was controlled.
Considering cognitive emotional regulation strategies,
insomniacs reported higher levels of rumination, self-blame,
acceptance, catastrophizing and lower levels of positive refocusing
than good sleepers. This result is expected as rumination, self-blame
and catastrophizing are cognitive emotional regulation processes
considered to be less adaptive35. The observation that insomniacs
revealed higher levels of acceptance is somewhat unexpected14.
Acceptance of a stressful life event has been negatively related
to anxiety symptoms14. A possible explanation for this result is
that insomniacs engage in a passive form of acceptance which is
more a form of resignation whereas an active form of acceptance,
involving self-affirmation, would be more adaptive35. As predictable
insomniacs revealed lower levels of positive refocus in comparison
with good sleepers. Although positive reappraisal is the cognitive
emotional regulation strategy most frequently associated with less
symptoms of depression and more adaptive35, positive refocus, i.e.
thinking about joyful and pleasant issues or about the steps to take
to solve a negative event is also a strategy that may help subjects to
experience less cognitive arousal and consequently insomnia.
When the effect of negative affect was controlled most
of cognitive emotional regulation processes were no longer
significantly different between sleep groups, except for rumination.
This result suggests that negative affect is a mediator activating
higher levels of self-blame, acceptance, catastrophizing and lower
levels of positive refocusing, compromising sleep. The fact that
rumination is still higher in insomniacs when negative affect is
controlled for is expected. Rumination and repetitive thinking
34 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35
are consistently associated with more sleep difficulties in the
literature12,14 and rumination has been associated with poor sleep
quality even when controlling for negative mood36.
Insomnia prevalence (15.1%) in our study was within the
prevalence range of a recent systematic review about this topic
within university students (9.4%-38.2%)1 and was higher in females
(17.1%) than in males (6.7%), as expected38. Early morning waking
was the most frequent insomnia symptom, followed by difficulties
initiating sleep and difficulties maintaining sleep. This result in
agreement with previous studies8,12.
Limitations of the research include: (i) cross-sectional design
of the study which makes it difficult to explore cause-effect
associations; (ii) the sample only included university students
and was mainly composed by woman (80.1%), jeopardizing
generalization of results to other populations; (iii) subjective reports
of sleep were obtained and not objective measures of sleep using
polysomnography or actigraphy which could have corroborate and
strengthen results; iv) insomnia definition followed general criteria
for insomnia diagnosis and was only a proxy of insomnia definition
postulated by the American Academy of Sleep Medicine (AASM)
in the third version of the International Classification of Sleep
Disorders (ICSD-338) or by the American Psychiatric Association
(APA) in the fifth edition of the Diagnostic and Statistical Manual
of Mental Disorders (DSM-539).
Conclusion
Individuals with insomnia revealed personality traits of neuroticism
and socially prescribed perfectionism, experienced their lives as
more stressful, used perseverative repetitive negative thinking to
Figure 1: Diagram: Psychological variables and Insomnia
cope with problems or negative life events and rumination as a
cognitive emotional regulation strategy to deal with a negative past
event (Figure 1). These results were not a result of negative affect.
Therefore, specific psychological factors contribute to cognitive
hyperarousal and predispose the individual to experience disturbed
sleep and consequently insomnia9. In future studies it could be
worth investigating whether psychotherapies focusing on coping
with the mentioned psychological variables could ameliorate
students insomnia and improve their well-being and academic
performance.
Conflicts of interests state
Authors have no conflict of interests or financial support to
disclosure.
Acknowledgment
Participation of university students and the collaboration of
lecturers are deeply appreciated.
References
1. Jiang XL, Zheng XY, Yang J, Ye CP, Chen YY, Zhang ZG, et al. A
systematic review of studies on the prevalence of insomnia in university
students. Public Health. 2015;129(12):1579–1584. doi:10.1016/j.
puhe.2015.07.030.
2. Taylor DJ, Bramoweth AD, Grieser EA, Tatum JI, Roane BM.
Epidemiology of insomnia in college students: relationship with
mental health, quality of life, and substance use difficulties. Behav Ther.
2013;44(3):339–348. doi:10.1016/j.beth.2012.12.001
 Amaral AP / Arch Clin Psychiatry. 2021;48(1): 29-35
3. Alsaggaf MA, Wali SO, Merdad RA, Merdad LA. Sleep quantity, quality,
and insomnia symptoms of medical students during clinical years.
Relationship with stress and academic performance. Saudi Med J.
2016;37(2):173–182. doi:10.15537/smj.2016.2.14288
4. van de Laar M, Verbeek I, Pevernagie D, Aldenkamp A, Overeem S. The
role of personality traits in insomnia. Sleep Med Rev. 2010;14(1):61–68.
doi:10.1016/j.smrv.2009.07.007
5. Mokros Ł, Witusik A, Michalska J, Łężak W, Panek M, Nowakowska-
Domagała K, et al. Sleep quality, chronotype, temperament and bipolar
features as predictors of depressive symptoms among medical students.
Chronobiol Int. 2017;34(6):708–720. doi:10.1080/07420528.2017.1316730.
6. Brand S, Kirov R, Kalak N, Gerber M, Pühse U, Lemola S, et al.
Perfectionism related to self-reported insomnia severity, but not when
controlled for stress and emotion regulation. Neuropsychiatr Dis Treat.
2015;11:263-271. doi: 10.2147/NDT.S74905.
7. Schmidt RE, Courvoisier DS, Cullati S, Kraehenmann R, der Linden MV.
Too Imperfect to Fall Asleep: Perfectionism, Pre-sleep Counterfactual
Processing, and Insomnia. Front Psychol. 2018;9:1288. doi:10.3389/
fpsyg.2018.01288.
8. Azevedo MH, Bos SC, Soares MJ, Marques M, Pereira AT, Maia B, et al.
Longitudinal study on perfectionism and sleep disturbance. World J Biol
Psychiatry. 2010;11(2-2):476-485. doi: 10.3109/15622970903304467.
9. Harvey CJ, Gehrman P, Espie CA. Who is predisposed to insomnia:
a review of familial aggregation, stress-reactivity, personality and
coping style. Sleep Med Rev. 2014;18(3):237–247. doi:10.1016/j.
smrv.2013.11.004
10. Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M, Perlis
M, et al. The hyperarousal model of insomnia: a review of the concept
and its evidence. Sleep Med Rev. 2010;14(1):19-31. doi: 10.1016/j.
smrv.2009.04.002.
11. Ehring T, Zetsche U, Weidacker K, Wahl K, Schönfeld S, Ehlers A. The
Perseverative Thinking Questionnaire (PTQ): validation of a content-
independent measure of repetitive negative thinking. J Behav Ther Exp
Psychiatry. 2011;42(2):225–232. doi:10.1016/j.jbtep.2010.12.003
12. Amaral AP, Soares MJ, Pinto AM, Pereira AT, Madeira N, Bos SC,
Marques M, Roque C, Macedo A et al. Sleep difficulties in college
students: The role of stress, affect and cognitive processes. Psychiatry
Res. 2018;260:331-337. doi: 10.1016/j.psychres.2017.11.072.
13. Takano K, Sakamoto S, Tanno Y. Repetitive thought impairs sleep
quality: an experience sampling study. Behav Ther. 2014;45(1):67-82.
doi: 10.1016/j.beth.2013.09.004.
14. Garnefski N, Kraaij V, Spinhoven P. Negative life events, cognitive emotion
regulation and emotional problems. Pers Indiv Differ., 2011;30(8):1311-
1327. doi.org/10.1016/S0191-8869(00)00113-6.
15. Kirwan M, Pickett SM, Jarrett NL. Emotion regulation as a moderator
between anxiety symptoms and insomnia symptom severity. Psychiatry
Res. 2017;254:40-47. doi: 10.1016/j.psychres.2017.04.028.
16. Zawadzki MJ, Graham JE, Gerin W. Rumination and anxiety mediate
the effect of loneliness on depressed mood and sleep quality in college
students. Health Psychol. 2013;32(2):212-222. doi: 10.1037/a0029007.
17. Simor P, Zavecz Z, Pálosi V, Török C, Köteles F. The influence of sleep
complaints on the association between chronotype and negative
emotionality in young adults. Chronobiol Int. 2015;32(1):1-10. doi:
10.3109/07420528.2014.935786.
18. Zunhammer M, Eichhammer P, Busch V. Sleep quality during
exam stress: the role of alcohol, caffeine and nicotine. PLoS One.
2014;3;9(10):e109490. doi: 10.1371/journal.pone.0109490.
19. Eysenck HJ, Eysenck SBG. The Eysenck Personality Inventory. London,
UK: University of London Press.1964.
20. Barton J, Spelten E, Totterdell P, Smith L, Folkard S, Costa G. The
Standard Shiftwork Index: a battery of questionnaires for assessing
shiftwork-related problems. Work stress. 1995;9(1):4-30.
21. Silva CF, Silvério JM. Versão Portuguesa do “Standard Shiftwork Index”:
Resultados com amostras portuguesas de enfermeiros [Portuguese
Version of the “Standard Shiftwork Index”: Results in Portuguese Nurse
Samples]. Psicologia: teoria, investigação e prática. 1997;2:233-240.
35
22. Frost RO, Marten P, Lahart C, Rosenblate R. The dimensions of
perfectionism. Cogn Ther Res. 1990;14(5):449-468. doi.org/10.1007/
BF01172967.
23. Amaral APM, Soares MJ, Pereira AT, Bos SC, Marques M, Valente J, et
al. Frost multidimensional perfectionism scale: Frost multidimensional
perfectionism scale: The Portuguese version. Arch Clin Psychiatry
(São Paulo). 2013;40(4):144-149. doi.org/10.1590/S0101-
60832013000400004.
24. Hewitt PL, Flett GL. Perfectionism in the self and social contexts:
conceptualization, assessment, and association with psychopathology. J
Pers Soc Psychol. 1991;60(3):456. doi.org/10.1037/0022-3514.60.3.456.
25. Soares M, Gomes A, Macedo A, Santos V, Azevedo MH. Escala
Multidimensional de Perfeccionismo: Adaptação à População
Portuguesa [Multidimensional Scale of Perfectionism: Adaptation to the
Portuguese Population]. Rev Port Psicossomática. 2003;5:46–55.
26. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived
stress. J Health Soc Behav. 1983;24(4):385-396. doi: 10.2307/2136404
27. Amaral AP, Soares MJ, Bos SC, Pereira AT, Marques M, Valente J, et al.
The Perceived Stress Scale (PSS-10)-a portuguese version. XVI World
Congress of Psychiatry, Madrid. Abstract Book. 2014;3:390.
28. Chaves B, Pereira AT, Castro J, Soares MJ, Macedo A. Questionário
de Pensamento Perseverativo: validação da versão portuguesa
[Perseverative thinking questionnaire: Portuguese version validation].
Psiquiatria clínica. 2013;34(3):155–162.
29. Garnefski N, Van Den Kommer T, Kraaij V, Teerds J, Legerstee J, Onstein
E. The relationship between cognitive emotion regulation strategies and
emotional problems: comparison between a clinical and a non‐clinical
sample. Eur J Personality. 2002;16(5): 403-420. doi.org/10.1002/per.458.
30. Castro J, Soares MJ, Pereira AT, Chaves B, Macedo A. Questionário da
Regulação emocional Cognitiva: validação para a população portuguesa
[Cognitive emotional regulation Questionnaire: validation of the
Portuguese version]. Psiquiatr Clín. 2013; 34(2):101–109.
31. McNair DM, Lorr M, Droppleman LF. Edits Manual for the Profile of
Mood States. San Diego, California: Educational and Industry Testing
Service; 1971.
32. Azevedo MH, Silva CF, Dias MR. O “Perfil de Estados de Humor”:
Adaptação à população portuguesa [The “Profile of Mood States”:
Adaptation to the Portuguese Population]. Psiquiatr Clín. 1991;12:187-
193.
33. Azevedo MHP, Bos SC. Saúde após o parto (3 meses) [Health after
Childbirth (3 months)]. Biblioteca Nacional de Portugal (Cota: S.A.
115132 V); 2005
34. Singareddy R, Vgontzas AN, Fernandez-Mendoza J, Liao D, CalhounS,
Shaffer ML, et al. Risk factors for incident chronic insomnia: a general
population prospective study. Sleep Med. 2012;13(4):346–353.
doi:10.1016/j.sleep.2011.10.033
35. Garnefski N, Kraaij V. Relationships between cognitive emotion
regulation strategies and depressive symptoms: A comparative study
of five specific samples. Pers Indiv Differ. 2006; 40(8):1659-1669. doi.
org/10.1016/j.paid.2005.12.009.
36. Thomsen DK, Mehlsen MY, Christensen S, Zachariae R. Rumination—
relationship with negative mood and sleep quality. Pers Indiv
Differ. 2003;34(7):1293-1301.doi.org/10.1016/S0191-8869(02)00120-4.
37. Bos SC, Macedo AF. Literature review on Insomnia (2010–2016). Biol
Rhythm Res. 2019;50(1):94-163. doi.org/10.1080/09291016.2017.14137
66
38. American Academy of Sleep Medicine, AASM. International
Classification of Sleep Disorders, ICSD, third ed. Darien, IL: American
Academy of Sleep Medicine; 2014.
39. American Psychiatric Association, APA. Diagnostic and Statistical
Manual of Mental Disorders (DSM-5), fifth ed. Arlington, VA: American
Psychiatric Association; 2013.
 Original article

Religiosity/spirituality, motivation and self-efficacy in the treatment of crack users

Amanda Ely
https://orcid.org/0000-0002-1975-9266
Bruno Paz Mosqueiro*
https://orcid.org/0000-0002-4405-0718

Grupo Hospitalar Conceição, Porto Alegre, Rio Grande do Sul,Brazil

Received: 21-02-2020 – Accepted: 09-11-2020

DOI: 10.1590/0101-60830000000276

ABSTRACT
Introduction: Religiosity and spirituality (R/S) are protective factors for substance use disorders. Despite that, few studies have evaluated
the impact of R/S on motivation and self-efficacy for abstinence, especially for crack-dependent patients.
Objectives: To verify the association between R/S, self-efficacy and motivation for change among crack users undergoing treatment.
Method: Quantitative study conducted with 50 patients from a CAPS AD III located in Porto Alegre from March to October 2018.
Assessments include the Duke Religion Index (DUREL), the World Health Organization Quality of Life, Spirituality, Religiousness and
Personal Beliefs instrument (WHOQOL-SRPB), the University of Rhode Island Change Assessment (URICA) and the Drug Abstinence
Self-Efficacy Scale (DASE).
Results: WHOQOL-SRPB (beta 0.519, p=0.00) and intrinsic religiosity (beta 0.475, p=0.00) were statistically significant correlated with
drug abstinence self-efficacy, controlling for socio-demographics. Intrinsic religiosity (r=0.32, p=0.02), non-organizational religiosity
(r=0.28, p=0.04), WHOQOL-SRPB (r=0.29, p=0.03) and WHOQOL-SRPB connect (r = 0.40, p = 0.00), meaning (r = 0.31, p = 0.02),
spiritual strength (r = 0.41, p = 0.00), and faith (r = 0.32, p = 0.02) were associated with the longest time in abstinence in life.
Conclusion: Results demonstrates that different aspects of R/S have a positive impact on the treatment of crack dependent patients.

Ely A / Arch Clin Psychiatry. 2021;48(1):36-44

Keywords: Religion, Spirituality, Motivation, Self-Efficacy, Crack-Cocaine

Introduction
The World Drug Report 2018 estimates that about 5.6% of the
world's population, about 275 million people make use of illicit
substances at least once a year1. In 2014, a national study showed
that the consumption of crack has already reached about 0.8%
of the population in Brazilian capital cities, which represent
approximately 370 thousand regular users, as well as in about 98%
of the Brazilian municipalities, also including those with less than
20,000 inhabitants2 .
Most crack users (62.8%) present positive criteria for
dependence even at the beginning of consumption, where there is
also a high rate of relapses even among those who are recovering
due to periods of intense craving associated with other withdrawal
symptoms such as fatigue, anhedonia and depression 3 . Studies
carried out aiming to qualify the offer of treatments for crack
addicts demonstrate that this population presents difficulties in
seeking and accessing health equipment, low motivation and high
rate of discharge due to evasion upon request and indiscipline4,5.
Among the therapeutic interventions that can favor adherence
to treatment and encourage changes in addictive behavior of crack
users, the Transtheoretical Model developed by Prochaska and Di
Clemente6 stands out. It is based on the premise that behavioral
change happens along a process in which people go through
different levels of motivation to change6,7. Such levels are known
as Stages of Change. The pre-contemplation stage reflects the
perceptions of the individuals not intending to make changes in
their drug consumption patterns, the contemplation involves the
recognition of problems and a wish to undertake changes, the action
Address for correspondence: Amanda Ely, Grupo Hospitalar Conceição, Rua Tiradentes, 35, 207, Bairro Independência. Porto Alegre-RS- 90560-030, Brazil. Tel: 55 (51) 3237 0712; Email: amandaelli@
gmail.com
stage reflects the initial changes in additive behaviors, whereas the
maintenance stage reflects the intent to sustain effective behavior
modifications and prevent relapses related to drug consumption8.
Appropriate therapeutic interventions are necessary to identify the
stage in which the patient is (pre-contemplation, contemplation,
preparation, action or maintenance) in order to use the appropriate
tools for the effectiveness of treatment8. Other factors that stimulate
motivation are the Mechanisms of Change, which are formed by
internal and external constructs that directly interfere in the process
of change between stages9. Among the mechanisms of change the
Abstinence Self-Efficacy stands out. It is defined as the set of beliefs
that people have about their own abilities, which is important to
deal with risk situations for relapse10,11.
Another dimension that has been studied in its importance
for the recovery of drug addicts is that of Religiosity/Spirituality
(R/S). For Koenig12, religion can be defined as an organized system
of beliefs, practices, rituals and symbols designed to facilitate
proximity to the sacred or transcendent. Spirituality is understood
as the personal search for answers to the final questions about life
and about the relationship with the sacred or transcendent, which
may (or may not) lead to the development of religious rituals.
The importance of these dimensions in the area of substance use
disorders has been growing based on studies with large population
groups and meta-analyses, which have already demonstrated an
inverse correlation between drug use and religious involvement13.
In a prospective study carried out in the United States with more
than 10,000 people undergoing treatment for addiction, it was
concluded that high rates of R/S involvement contributed to a
reduction in relapse rates as well as in a frequency and quantity
37 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44
decrease of use of all different drug types14.
Thus, seeking to broaden the understanding of factors that can
contribute to the recovery of crack addicts, the objective of the
present study is to verify the existence of a relationship between
R/S, motivation for change and self-efficacy for abstinence,
understanding how greater or lesser levels of religiosity interfere
with the acquisition of skills to perform the treatment interventions
for crack use. The research was conducted at a Psychosocial
Attention Center for Alcohol and Drugs - CAPS AD III where
crack users undergoing treatment were interviewed. So far, we are
unaware of other studies that have evaluated the same constructs
for this population.
Method
Study Design and Sampling
This research was characterized as quantitative cross-sectional
study, where 50 crack users in treatment were interviewed at the
Psychosocial Attention Center for Alcohol and Drugs - CAPS
AD III of Grupo Hospitalar Conceição in Porto Alegre-RS in the
period between March to October 2018. Originally a sample size
of 68 individuals was estimated to identify moderate effect size
correlations (>0.30) between religiosity domains, motivation and
self-efficacy, for a level of statistical significance with a p <0.05.
During the research, 50 individuals were identified for interviews
by one of the authors (AE) available for in person interviews once
a week at CAPS AD III. Inclusion criteria were being over 18 years
old, presenting a diagnosis of current crack addiction based on the
ICD-10 and being linked to the treatment offered at CAPS AD.
The exclusion criteria include the existence of cognitive deficits
or psychiatric comorbidity that could affect the understanding of
the questions asked. Patients who met the inclusion criteria were
personally approached by the author while waiting for consultations,
being invited to participate in the study. All approached patients
accepted the invitation and 47 of them completed all the
assessments. The Free and Informed Consent Term was read for all
the patients, which was duly signed in compliance with the current
ethical standards.
Research Instruments
Socio-demographics, consumption patterns and religiosity/
spirituality
For the purpose of this study, a structured questionnaire was
designed by the researchers in order to collect data on age, residence
conditions, education, work, perception of relevance of religiosity/
spirituality in the treatment and the religious profile of the sample.
Social economic classes were evaluated according the Brazilian
Economic Classification Criteria15.
One question retrieved from the “Addiction Severity Index
(ASI)" validated into Brazilian Portuguese, was adapted to evaluate
the frequency of crack consumptiom reported by patients within
the last 30 days of the interview (e.g. 1-3 times a month, 1-2 times
per week, 3-6 times per week, daily consumption, abstinent more
than a month) 16. We carried out a pilot interview test before data
collection.
The Duke University Religion Index (DUREL)
We used the DUREL scale, which is a five-item measurement of
religious involvement17. This scale was translated and validated
for the Brazilian population18. It measures three of the main
dimensions of religious involvement, relating them to health
outcomes: organizational religiosity (OR) (attendance to religious
activities); non-organizational religiosity (NOR) (frequency of
private religious activities such as prayers, meditation or religious
readings) and intrinsic religiosity (IR) (internalization and inner
experience of religiosity).
Spirituality and Quality of Life Questionnaire WHOQOL-SRPB
We also used the WHOQOL-SRPB in the measurement of
spirituality, which is an instrument developed to assess how
spirituality, religion and personal beliefs (SRPB) are related to
quality of life (QOL) in health and health care19. It is a specific
module developed by the World Health Organization Quality of
Life in the context of the WHOQOL-100 instrument, domain SRPB
(Spirituality, Religiousness and Personal Beliefs), which has eight
facets: meaning of life, awe, wholeness and integration, spiritual
strength, inner peace/serenity/harmony, hope and optimism
and faith. Each facet is evaluated by four questions, totaling 32
questions20.
University of Rhode Island Change Assessment (URICA)
To assess motivational stages for change we used the URICA scale
originally developed in 1983 by McConnaughy, Prochaska and
Velicer21. The URICA scale was validated and adapted for Brazil
by Szupszynski and Oliveira7 to be used in psychoactive substance
users. It consists of 24 items answered with the Likert scale of one
to five items, where four motivational stages are evaluated and
divided into six items: pre-contemplation, contemplation, action
and maintenance.
Drug Abstinence Self-Efficacy (DASE)
We used the DASE scale to measure the self-efficacy, which aims
to measure confidence and the ability to maintain abstinence in
situations of contexts for the use of substances from the Likert
scale of one to five items, measuring the potential for self-efficacy
in 24 questions. This scale was translated and validated for Brazil
by Freire et al11
Statistical Analysis
We used a descriptive approach to assess the clinical and socio-
demographic variables of the individuals under study, describing
their profiles. Linear regression analyses were used to evaluate the
association between R/S, motivational stages for change and drug
abstinence self-efficacy, controlling for the main sociodemographic
variables (age, sex and education). As secondary outcomes Pearson
correlation analysis evaluated the univariate associations between
R/S, age of first crack consumption, age of search for treatment and
the longest time of crack-cocaine abstinence in life after the first
crack consumption. For the performed analyses, a level of statistical
significance was used with a p <0.05.
Ethical Aspects
The study was approved by the Research Ethics Committee of
Grupo Hospitalar Conceição (CAAE 79747217.1.0000.5530).
Results
Socio-Demographic Profile
We investigated the socio-demographic profile of the participants,
where 86% were male with an average age of 40.9 years, with a
minimum age of 21 years and a maximum of 64 years. The majority
referred to themselves as white (60%) and single (52%) or separated
(32%). Respondents in general had low education with an average
of 7.3 years of study and most of them were unemployed (34%)
 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44 38

or working informally (28%). Only two respondents were working
at a regular job at the time of the survey. 40% of respondents said
they received some type of social benefit such as: sick pay (45%),
family allowance (25%) and disability retirement (15%). Housing
conditions varied between owing a house (36%), renting a house
(18%) and being homeless (22%). The economic characteristics of
the interviewees’ demonstrated situations of social vulnerability,
where most of them could be classified as belonging to social class
E (Table 1).
Substance Use
Regarding their history of substance use, 98% of the interviewees
reported the use of some substance associated with crack, among the
most frequent were tobacco (78%), alcohol (76%), marijuana (54%)
and inhaled cocaine (48%). Only one (01) interviewee declared to
use crack exclusively. The pattern of use demonstrated that when
relapsing, 48% of respondents used crack daily and 23% about 3
to 6 times a week. The average age of first-time crack consumption
was 27.5 years, and an average age for seeking treatment of 31.5
years, with an average of 3.9 years interval between the age of use
onset seeking for treatment. Most of the interviewees (96%) had
already undergone previous treatments for crack use, where the
longest abstinent time between first time consumption and the
current time has an average period of 18.5 months. The treatment
places prior to CAPS AD were: Hospitalizations (80%), Therapeutic
Communities (60%), Mutual Aid Groups (46%) and Primary Care
(26%) (Table 1).
Religious Profile, Crack Addiction Treatment and
Abstinence
The interviewees' religious denominations in order of frequency
were: Catholic (44%), Evangelical (18%), Spiritual But Not
Religious (18%), Spiritism (8%), Afro-Brazilian Religions (6%) and
Others (2%). Two respondents (4%) claimed to be atheists. Twenty-

Table 1. Clinical and Sociodemographic Characteristics of Crack Dependent Patients at CAPS AD III (n = 50)
Frequency Percentage (%)
Sex
Female
7 14.0 %
Male
43 86.0 %

Skin Color
White
30 60.0 %
Brown/Black
20 40.0 %

Marital Status
Never had a partner
26 52.0 %
With partner
8 16.0 %
Separated
16 32.0 %
Widower/widow
0 0

Socioeconomic Classes*
B2 (average income 4.850 BR)
3 6.0 %
C (average income 2000 BR)
15 30.0 %
D (average income 714 BR)
10 20.0 %
E (average income 477 BR)
22 44.0 %

Crack Usage Frequency

1-3 times a month 5
10.0 %
1-2 times a week 8
16.0 %
3-6 times a week 13
26.0 %
Daily 24
48.0 %

Associated Substance Use

Tobacco 39 78.0 %
Alcohol 38 76.0 %
Inhaled Cocaine 24 48.0 %
Marijuana 27 54.0 %
Benzodiazepines 5 10.0 %
Solvents 8 16.0 %
Amphetamines 1 2.0 %
Hallucinogens 3 6.0 %

Previous Treatment
Without previous treatment
2 4.0 %
Primary care
13 26.0 %
Private care
6 12.0 %
Self-help groups
23 46.0 %
CAPS (Psychosocial Attention Center)
40 80.0 %
Psychiatric Hospitalizations
40 80.0 %
Therapeutic Communities
30 60.0 %

*For patients reporting abstinence for over one month (17/50)

* Average family income estimated in Brazilian Reais (BR) by the Brazilian Economic Classification Criteria
(2010).
39 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44

Table 1. Continuation for continuous variables.

Variation Average (Standard Deviation)

Age, Education and Crack Treatment

Age (n=47) 21-64 40.9 9.4
Years of study (n=50) 1-17 7.3 3.3

Age of crack use onset (n=50) 12-53 27.5 11.1

Age of seeking for treatment (n=50) 12-55 31.5 10.8
Current abstinent time in months* (n=17) 1-48 7.91 15.3
Longest abstinent time lifetime in months (n=50) 0-96 18.1 21.1
Individual income (BRL) (n=50) BRL 0-2.500,00 BRL 765,00 BRL 599,00

URICA Motivation Scale (n=50)

Pre-contemplation 6-23 14.2 2.8
Contemplation 12-27 22.6 2.5
Action 12-29 23.8 3.2
Maintenance 8-30 23.3 3.9

Self-Efficacy Scale (n=50) 24-113 66.3 20.3

*From 50 patients interviewed, 17 reported being abstinent of crack consumption for a month or more.

four percent said they attended more than one religion. Most of
the interviewees (94%) said they considered important questioning
on the part of health professionals about spirituality and religiosity,
however only 24% stated that this issue had already been addressed
in consultations (Table 2).
No statistically significant associations were identified between
the domains of the WHOQOL SRPB and the DUREL religiosity
scale with age of first crack consumption or age of seeking treatment.
The longest time in abstinence in life after the first crack
consumption was positively correlated to intrinsic religiosity
(r=0.32, p=0.02), non-organizational religiosity (r=0.28, p=0.04),
the global score of the WHOQOL-SRPB (r=0.29, p=0.03) and
WHOQOL-SRPB domains connect (r = 0.40, p = 0.00), meaning
in life (r = 0.31, p = 0.02), spiritual strength (r = 0.41, p = 0.00), and
faith (r = 0.32, p = 0.02).
Religiosity/Spirituality and Motivation for Change
A multilinear regression model evaluated the association between
R/S variables and motivational stages for change, controlling for
age, sex and education. The WHOQOL-SRPB was statistically
significant associated with pre-contemplation stage (beta 0.351,
p=0.01) and action stage (beta 0.273, p=0.05). No statistically
significant associations were identified between the WHOQOL
SRPB with contemplation and maintenance stages <table 3>.
No statistically significant associations were identified between
the DUREL dimensions and the motivational stages of pre-
contemplation, contemplation, action and maintenance stages on
the URICA scale <table 3>.
Religiosity/Spirituality and Drug Abstinence Self-Efficacy
A linear regression model evaluated the association between
R/S variables and self-efficacy for drug abstinence scale (DASE),
controlling for age, sex and education levels <Table 4>. The
WHOQOL-SRPB (beta 0.519, p=0.00) and intrinsic religiosity
(beta 0.475, p=0.00) were statistically significant associated with
self-efficacy for abstinence, controlling for socio-demographics
(Table 4).
Discussion
The present study has identified a significant association between
different domains of religiosity/spirituality and self-efficacy and
longer time in abstinence lifetime in patients with crack addiction
treated at a CAPS AD III in Porto Alegre-RS.
The profile of those surveyed was similar to that found in a
national survey of crack users residing in Brazilian capitals, that is,
mostly young men with little education who do not have a job/fixed
income2. In relation to other studies that present a profile of young
users2,22-24, generally in the 30-year age range, our sample differed by
the significantly higher average age (40.9 years), showing variations
in the population profile from one region to another, where the
use of crack has become popular among users of all ages. We also
observed the large number of respondents declaring themselves
single or separated (84%), exceeding the same proportion of people
living without a partner in the Brazilian population (65.1%) as
according to the 2010 Census25. This data, also found in similar
studies, may indicate that the use of crack causes damage to the
constitution and maintenance of the family group. The question
of skin color was different from other studies, where 60% of users
referred to themselves as being white, even surpassing national
epidemiological data, where the white population is estimated
in 48%25, which we believe may be related regional specificities.
Anyway, the social vulnerability condition was evident, both related
to the low level of education of most of the interviewees, as well
as in the occupational condition and the social class identified
through questions about housing conditions and income.
The vast majority of patients (98%) claimed to consume
substances other than crack, with a predominance of tobacco (78%)
and alcohol (76%), similarly to that found in the epidemiological
survey conducted by Senad23, characterizing crack users as multi-
users and this substance being one more in a broad "portfolio" of
psychoactive substances. The short period of time between the
beginning of consumption and seeking for care (less than 4 years)
can indicate immediate harmful effects related to the use of crack,
 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44 40

Table 2. Religiosity and Spirituality in Crack Dependent Patients seen at CAPS AD III in Porto Alegre, Brazil (n = 50)

Religious Denomination Freq. Pct. (%)

Catholic 22 44.0%
Evangelic 9 18.0%
Spiritism 4 8.0%
Afro-Brazilian Religions 3 6.0%
Without religion, with spirituality 9 18.0%
Atheist 2 4.0%
Attends more than one religion 12 24.0%

Organizational Religiosity (DUREL 1) * Freq. Pct. (%)

More than once a week 8 16.0%
Once a week 10 20.0%
Two to three times a month 16 32.0%
A few times a year 7 14.0%
Once a year or less 7 14.0%
Never 2 4.0%

Non-Organizational Religiosity (DUREL 2) ** Freq. Pct. (%)

More than once a day 14 28.0%
Two or more times a week 1 2.0%
Once a week 9 18.0%
A few times a month 20 40.0%
Rarely or never 6 12.0%

Intrinsic Religiosity (DUREL 3-5) *** Freq. Pct. (%)

High (> = 10 points) 35 70.0%

WHOQOL Spirituality, Religiosity and Personal Beliefs (SRPB) Avg. Standard Deviation
Connection with self or spiritual strength 3.1 1.1
Meaning in life 3.4 0.95
Admiration 3.8 1.0
Wholeness & integration 3.0 0.92
Spiritual strength 3.3 1.0
Inner peace 2.8 1.0
Hope and optimism 3.3 0.92
Faith 3.4 1.1
Total 13.2 3.2

Questionnaire on religiosity and treatment Pct. (%)

Yes (94.0%)
Do you think it is important for health professionals to ask about religiousness and spirituality in health care?
No (6.0%)
Yes (24.0%)
Have any health professionals ever asked about your religious beliefs or spirituality in your health care?
No (76.0%)
Patients who underwent treatment in therapeutic communities (n=33)
Yes (97.0%)
Does the therapeutic community have a religious orientation?
No (3.0%)
Yes (43.8.0%)
Was the religious orientation the same as yours?
No (56.3%)
Yes (78.1%)
Do you feel that your religious belief was respected?
No (21.9%)

*Church, temple or other religious gathering attendance. **Individual religious activities such as prayers, meditations, reading the Bible or other
religious texts. ***Subjective perception and degree of motivation and involvement with religiosity.
 41 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44

Table 3. Multilinear regression models of religiosity dimensions and motivational stages for change among crack-cocaine patients (N=47)
Predictors Pre-Contemplation Contemplation
Adjusted R-Square Adjusted R-Square
Model 1 Beta t Sig. (0.16, P=0.01) Beta t Sig. (0.08, P=0.09)
Age -0.354 -2.584 0.01 0.183 1.270 0.21
Sex -0.036 -0.259 0.79 0.192 1.334 0.18
Education (years of study) -0.121 -0.871 0.38 0.221 1.517 0.13
WHOQOL-SRPB 0.351 2.525 0.01 0.260 1.784 0.08

Adjusted R-Square Adjusted R-Square

Model 2 Beta t Sig. (0.07, P=0.12) Beta t Sig. (0.03, P=0.23)
Age -0.305 -2.124 0.04 0.213 1.459 0.15
Sex -0.042 -0.291 0.77 0.184 1.242 0.22
Education (years of study) -0.203 -1.407 0.16 0.178 1.210 0.23
Organizational Religiosity (DUREL) 0.170 1.195 0.23 -0.134 -0.926 0.36

Adjusted R-Square Adjusted R-Square

Model 3 Beta t Sig. (0.08, P=0.09) Beta t Sig. (0.02, P=0.31)
Age -0.359 -2.447 0.01 0.207 1.363 0.18
Sex -0.046 -0.320 0.75 0.185 1.241 0.22
Education (years of study) -0.184 -1.285 0.20 0.170 1.150 0.25
Non-organizational Religiosity
0.209 1.438 0.15 0.038 0.253 0.80
(DUREL)

Adjusted R-Square Adjusted R-Square

Model 4 Beta t Sig. (0.10, P=0.07) Beta t Sig. (0.02, P=0.28)
Age -0.348 -2.424 0.02 0.203 1.358 0.18
Sex -0.061 -0.424 0.674 0.180 1.206 0.23
Education (years of study) -0.149 -1.037 0.30 0.184 1.225 0.22
Intrinsic Religiosity (DUREL) 0.237 1.643 0.10 0.083 0.556 0.58

*statistically significant results in bold.

Table 4. Continuation. Multilinear regression models of religiosity dimensions, pre-contemplation and readiness for change among crack addicted patients (N=47)
Predictors Action Maintenance
Adjusted R-Square Adjusted R-Square
Model 1 Beta t Sig. (0.16, P=0.02) Beta t Sig. (0.009, P=0.47)
Age 0.375 2.726 0.00 0.253 1.672 0.10
Sex 0.129 0.938 0.35 0.022 0.143 0.88
Education (years of study) 0.048 0.343 0.73 0.135 0.881 0.38
WHOQOL-SRPB 0.273 2.964 0.05 -0.041 -0.267 0.79

Adjusted R-Square Adjusted R-Square

Model 2 Beta t Sig. (0.14, P=0.03) Beta t Sig. (0.005, P=0.44)
Age 0.415 3.000 0.00 0.246 1.643 0.10
Sex 0.125 0.895 0.37 0.022 0.144 0.88
Education (years of study) -0.021 -0.153 0.87 0.148 0.986 0.33
Organizational Religiosity (DUREL) 0.215 1.565 0.12 -0.073 -0.491 0.62

Adjusted R-Square Adjusted R-Square

Model 3 Beta t Sig. (0.09, P=0.09) Beta t Sig. (0.003, P=0.39)
Age 0.402 2.747 0.00 0.275 1.795 0.08
Sex 0.122 0.849 0.40 0.024 0.157 0.87
Education (years of study) -0.006 -0.041 0.96 0.139 0.929 0.35
Non-organizational Religiosity
0.033 0.231 0.81 -0.116 -0.763 0.45
(DUREL)

Adjusted R-Square Adjusted R-Square

Model 4 Beta t Sig. (0.11, P=0.05) Beta t Sig. (0.01, P=0.31)
Age 0.383 2.698 0.01 0.275 1.837 0.07
Sex 0.111 0.782 0.43 0.034 0.229 0.82
Education (years of study) 0.022 0.155 0.87 0.113 0.752 0.45
Intrinsic Religiosity (DUREL) 0.164 1.147 0.25 -0.169 -1.123 0.26
 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44 42

Table 4. Multilinear regression models of religiosity dimensions and drug abstinence self-efficacy among crack
dependent patients (N=47)
Predictors Drug Abstinence Self-Efficacy
Adjusted R-Square
Model 1 Beta t Sig.
Age -0.119 -0.895 0.37
Sex -0.154 -1.161 0.25
Education (years of study) 0.263 1.953 0.05 (0.23, P=0.00)
WHOQOL-SRPB 0.519 3.850 0.00

Adjusted R-Square
Model 2 Beta t Sig.
Age -0.050 -0.348 0.73
Sex -0.126 -0.859 0.39
Education (years of study) 0.144 0.988 0.32 (0.06, P=0.15)
Organizational religiosity (DUREL) 0.321 2.214 0.03

Adjusted R-Square
Model 3 Beta t Sig.
Age -0.144 -0.983 0.33
Sex -0.150 -1.045 0.30
Education (years of study) 0.177 1.234 0.22 (0.09, P=0.08)
Non-organizational religiosity (DUREL) 0.375 2.563 0.01

Adjusted R-Square
Model 4 Beta t Sig.
Age -0.131 -0.952 0.34
Sex -0.187 -1.365 0.18
Education (years of study) 0.245 1.773 0.08 (0.18, P=0.01)
Intrinsic Religiosity (DUREL) 0.475 3.423 0.00

which leads the person to seek for help and hospital admissions are
the most used means of treatment.
When it comes to the characterization of religiosity the
results showed a high level of religious involvement, where 78%
said they had some religious denomination, 18% had no religion,
but cultivated some kind of spirituality and only 2% said they
were atheists. The data are slightly different from those found in
the Brazilian population, where 95% said they have a religion26,
probably due to the inclusion of the option spiritual without
religion, which was absent in that study.
From this research it was possible to state that crack users who
had a higher score on the intrinsic religiosity measure (DUREL)
have a higher self-efficacy index for abstinence, being more able
to abstain from addictive behavior, improving the chances of
recovery. Better self-efficacy rates for abstinence were also found
in patients who had better scores on the WHOQOL-SRPB scale,
demonstrating greater spirituality from better scores on constructs
such as connection with some higher power, peace and meaning
in life, capacity for admiring things around its surroundings and
wholeness and integration to the environment.
Research indicates that low self-efficacy is associated with
relapse and conversely, self-efficacy is positively correlated with
abstinence27. Likewise, it can be said that stronger spirituality and
religious involvement can reduce relapse rates, favoring recovery24.
These data were based on the present study, since the interviewees
who obtained the best scores in spirituality/religiosity, mainly
intrinsic religiosity (IR) and the connection domains (r = 0.40, p
= 0.00), meaning in life (r = 0.31, p = 0.02), spiritual strength (r =
0.41, p = 0.00), and faith (r = 0.32, p = 0.02) as well as in the general
score of the scale WHOQOL-SRPB were also the ones who had
the longest periods of abstinence. In this particular association, to
remain abstinent for longer, it seems to matter less the individual's
religious denomination and frequency in places of organized
religion, and more what we can call spirituality, related to faith,
spiritual connection and capacity to perceive a meaning in life. In
another study, the intrinsic religiosity (IR) measure was associated
with less desire to consume the substance and a better quality of life
in all dimensions evaluated24.
Regarding motivational stages, the pre-contemplation and
action stages, were both differently associated with WHOQOL-
SRPB scores. In this respect, the association between WHOQOL-
SRPB with pre-contemplation might be explained by the fact that
in the early stages of drug consumption individuals might present
more difficulties to perceive or report problems or interferences in
their spirituality or quality of life. The association with WHOQOL-
SRPB with the action stage, otherwise, might be explained by an
increase in spiritual quality of life observed with initial changes and
movements toward crack-cocaine recovery. We question whether
abstinence causes people to seek more religious involvement,
feeling more integrated with their spirituality and developing their
faith more, or whether it is the recovery process, in the success in
carrying out the tasks of each phase that strengthens the religious or
spiritual practice. We believe more in the second hypothesis, since
the increase in self-efficacy for abstinence, which is a construct of
motivation, was directly related to all the R/S measures used in the
study.
Most respondents (94%) considered the questioning about R/S
in treatment contexts important, although only a small portion
43 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44
(24%) was questioned about the subject during some type of
health care. These data reinforce assumptions recommended by
the World Psychiatric Association28, showing that values, beliefs
and practices related to R/S remain relevant to the majority of
the world population and that patients would like to have their
R/S issues addressed in health care. Therefore, there is a demand
for inclusion of these dimensions in the assistance to crack users,
who often end up being delegated to religious institutions that
carry out some type of intervention with chemical dependents.
A recent study carried out in an inpatient unit for detoxification
demonstrated the need to expand and diversify activities aimed at
addressing patients' spirituality to the detriment of group activities
aimed at religious beliefs, thus respecting the necessary secularism
in health services29. In this sense, it is important to consider the
patients' religious beliefs and practices as an essential component
of the collection of psychiatric history, where spiritual anamnesis
has been widely used in clinical practice, which already has more
than twenty-five validated instruments aiming to improve patient’s
adhesion to treatment, satisfaction with received care and general
health outcomes28,30.
As suggestions for future studies, we understand there is a need
to expand the assessment of religiosity/spirituality with crack users
in other contexts and different locations in the country, as well as
new research that can deepen the knowledge of the relationship
between R/S and motivation, maybe acting as the basis for new
interventions in this area.
The results presented need to be observed considering some
limitations. The cross-sectional evaluation between the variables
does not allow causal inferences and prospective studies need
to be carried out to better understand the relationship between
religiosity, spirituality, motivation and self-efficacy. The profile of
crack-dependent patients seen at a CAPS AD III, located in the
southern Brazil, which is already linked to treatments, may not
represent the entire population of users. The study additionally do
not control for the effects of multiple psychiatric and social variables
that might interfere with results, including for instance psychiatric
comorbidities or the effects of other substances. However, the
originality of the findings and the consistency of the correlations
between religiosity, spirituality and self-efficacy, corroborated
by a longer period of abstinence throughout life, strengthen the
study and its validity when considering the importance of these
dimensions in the treatment of dependent individuals, which should
be considered in the treatment of crack-dependent patients and are
still infrequently addressed in clinical practice. Although generally
unrelated to early motivational stages, religiosity and spirituality
showed a significant association with self-efficacy and increased
abstinence lifetime after the first crack consumption. Such findings
reinforce the importance of addressing these dimensions in the
treatment of addiction disorders.
Name and address of the institution where the study was
conducted
Grupo Hospitalar Conceição
Av. Francisco Trein, 596- Cristo Redentor. Porto Alegre-RS.
91350-200
REFERENCES
1. United Nations Office on Drugs and Crime- UNODOC. World Drug
Report 2018. New York: United Nations publication, 2018.
2. Bastos FI, Bertoni N. Pesquisa Nacional sobre Uso de Crack: quem são
os usuários de crack e/ou similares no Brasil? Quantos são nas capitais
brasileiras? Rio de Janeiro: Editora ICICT/FIOCRUZ; 2014.
3. Associação Brasileira de Psiquiatria. Abuso e Dependência: Crack. Ver
Assoc Med Bras. 2012;58(2):141-53.
4. Ribeiro M, Laranjeira R, organizadores. O Tratamento do Usuário de
Crack. Porto Alegre: Artmed; 2012.
5. Ferreira ACZ, Capistrano FC, Maftum MA, Kalinke LP, Kirchhof
ALC. Caracterização de internações de dependentes químicos em uma
unidade de reabilitação. Cogitare Enferm. 2012;17(3):444-51.
6. Prochaska JO, Diclemente C. Transtheorical therapy: Toward a more
integrative model of change. Psycotherapy: Theory, Research and
Practice. 1982;20:161-73.
7. Szupszynski KPDR, Oliveira MS. O Modelo Transteórico no tratamento
da dependência química. Psicologia: teoria e prática. 2008;10(1):162-73.
8. Ávila AC, Yates MB, Silva DC, Rodrigues VS, Oliveira MS. Avaliação
da autoeficácia e tentação em dependentes de cocaína/crack após
tratamento com o modelo transteórico de mudança (MTT). Aletheia.
2016;49:74-88.
9. Szupszynski KPDR, Sartes LMA, Andretta I, Oliveira MS. Processos
de mudança cognitivos e comportamentais em usuários de crack em
tratamento. Revista Brasileira de Terapias Cognitivas. 2014;10(1):11-18.
10. Diclemente CC, Fairhurst SK, Piotrowski NA. Self-efficacy and addictive
behaviors. In Maddux JE (Ed.), Self-efficacy, adaptation and adjustment:
theory, research and application New York, NY: Plenum Press, p.109-
141; 1995.
11. Freire SD, Silva DC, Ávila AC, DiClemente C, Oliveira MS. Adaptation
and Validation of the Brazilian DASE and TUD Scales for Cocaine/
Crack Users. Paidéia . 2017;27(67):93-99.
12. Koenig H. Handbook of religion and health: a century of research
reviewed. University Press, Oxford, 2001.
13. Moreira-Almeida A, Lotufo Neto F, Koenig HG. Religiousness and
mental health: a review. Brazilian Journal of Psychiatry. 2006;28(3):242-
250.
14. Schoenthaler SJ, Blum K, Braverman ER, Giordano J, Thompson B,
Oscar-Berman M, et al. NIDA-Drug Addiction Treatment Outcome
Study (DATOS) Relapse as a Function of Spirituality/Religiosity. J
Reward Defic Syndr. 2015;1(1):36-45.
15. Associação Brasileira de Empresas de Pesquisa- ABEP. Critério de
Classificação Econômica Brasil. [Internet]. São Paulo: ABEP; 2019.
16. Kessler F, Cacciola J, Alterman A, Faller S, Souza-Formigoni ML, Cruz
MS, et al. Psychometric properties of the sixth version of the Addiction
Severity Index (ASI-6) in Brazil. Brazilian Journal of Psychiatry.
2010;34(1),24-33.
17. Koenig HG, Meador K, Parkerson G. Religion Index for Psychiatric
Research: a 5-item Measure for Use in Health Outcome Studies. Am J
Psychiatry. 1997;154:885-86.
18. Taunay TCD, Gondim FAA, Macêdo DS, Moreira-Almeida A, Gurgel
LA, Andrade LMS et al. Validação da versão brasileira da escala
de religiosidade de Duke (DUREL). Rev. psiquiatr. clín. [online].
2012;39(4):130-35.
19. Fleck MP; Skevington S. Explicando o significado do WHOQOL-
SRPB. Rev. psiquiatr. clín. [online]. 2007;34(1):146-49.
20. Fleck MP, Borges ZN, Bolognesi G, Rocha NS. Desenvolvimento
do WHOQOL, módulo espiritualidade, religiosidade e crenças
pessoais. Rev. Saúde Pública. 2003;37(4):446-55.
21. Mcconnaughy EA, Prochaska JO, Velicer WF. Stages of change in
psychotherapy: measurement and samples profiles. Psychotherapy:
Theory, Research & Practice. 1983;20(3):368-75.
22. Horta RL, Horta BL, Rosset AP, Horta CL. Perfil dos usuários de crack
que buscam atendimento em Centros de Atenção Psicossocial. Cad.
Saúde Pública. 2011;27(11):2263-70.
23. Ministério da Saúde (BR). Secretaria Nacional de Políticas sobre Drogas.
Perfil dos usuários de crack e/ou similares no Brasil. [Internet]. Brasília:
SENAD; 2013.
24. Rezende-Pinto A, Moreira-Almeida A, Ribeiro M, Laranjeira R, Vallada
H. The effect of religiosity during childhood and adolescence on drug
consumption patterns in adults addicted to crack cocaine. BJPsych
Open. 2018;4(5):324-31.
25. Instituto Brasileiro de Geografia e Estatística (IBGE). Censo
Demográfico 2010- Características gerais da população, religião e
pessoas com deficiência. Rio de Janeiro: IBGE; 2010.
26. Moreira-Almeida A, Pinsky I, Zaleski M, Laranjeira R. Envolvimento
religioso e fatores sociodemográficos: resultados de um levantamento
nacional no Brasil. Rev. psiquiatr. clín. 2010;37(1):12-15.
 Ely A / Arch Clin Psychiatry. 2021;48(1): 36-44 44

27. Figlie NB, Bordin S,Laranjeira R, organizadores. Aconselhamento em
dependência química. São Paulo: Roca; 2004.
28. Moreira-Almeida A, Sharma A, Van Rensburg BJ, Verhagen PJ, Cook
CC. WPA Position Statement on Spirituality and Religion in Psychiatry.
World Psychiatry. 2016;15(1):87-8.
29. Ely A, Calixto AM. Religiosidade e espiritualidade no tratamento
hospitalar das adições. Rev. Bioét. [Internet]. 2018;26(4):587-596.
30. Moreira-Almeida A, Koenig HG, Lucchetti G. Clinical implications of
spirituality to mental health: review of evidence and practical guidelines.
Rev. Bras. Psiquiatr. 2014;36(2): 176-182.
 Original article

Personality structure evaluation: differences between clinical and non-clinical samples

using the Inventory of Personality Organization (IPO)
Carolina Rabello Hessel1
https://orcid.org/0000-0001-7701-5532
Sergio Eduardo Silva Oliveira2
https://orcid.org/0000-0003-2109-4862
Vânia Silva Lugo1
Vanessa Volkmer1
Rochelle Affonso Marquetto1*
https://orcid.org/0000-0002-0210-1935
Luis Souza Motta3,4
https://orcid.org/0000-0002-0206-1590
César Luís de Souza Brito1,4
https://orcid.org/0000-0002-2509-7270
Marco Antônio Pacheco1,4
Lucas Spanemberg1,3,4
https://orcid.org/0000-0001-6789-7420

1Núcleo de Formação em Neurociências da Escola de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil
2Departamento de Psicologia Clínica – Universidade de Brasília (UnB), Brasília, DF, Brazil
3Seção de Afeto Negativo e Processos Sociais, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
4Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil

Received: 22-09-2019 – Accepted: 17-11-2020

DOI: 10.1590/0101-60830000000277

Hessel CR / Arch Clin Psychiatry. 2021;48(1):45-50

Introduction by pathological identity diffusion, primitive defensive operations,

Personality is a wide construct, represented in psychoanalytic
theory as a dynamic integration of the totality of a person’s subjective
experience and behavior patterns, including both conscious
and unconscious experiences and views, behavior patterns, and
mental states1. The term “structure” refers to an organization of
related functions or processes that is relatively stable and enduring
over time; a configuration of mental functions or processes that
organize the individual’s behavior and subjective experience2.
Most of the current categorical and dimensional classifications of
personality are limited since they anchor themselves in observable
behaviors (personality traits) that predominantly refer to "surface
structures" of deeper underlying psychological structures. In this
way, Kernberg defines the normal personality structure as a set of
structural makings characterized by an integrated concept of the
self and an integrated concept of significant others, an integrated
identity, an integrated and mature system of internalized values,
and an appropriate and satisfactory management of needs, fears,
wishes, and impulses2.
Kernberg’s concept of personality structure includes a psychotic
personality organization2. It is characterized by lack of integration
of the concept of self and significant others (identity diffusion), a
predominance of defensive operations centering around splitting
(primitive defenses), and loss of reality testing. Among these
normal/pathological poles are the so-called neurotic and borderline
personality organizations. While the first is distinguished from the
normal personality on the basis of character rigidity, Borderline
Personality Organization (BPO) is a more severe level, characterized
and varying degrees of pathology of the internalized value systems.
The BPO includes all of the severe personality disorders seen in
clinical practice — typically borderline, schizoid and schizotypal,
paranoid, hypomanic, hypochondriacal, narcissistic (including
malignant narcissism syndrome), and antisocial3.
Nosographic changes presented by the introduction of the
America Psychiatric Association Diagnostic and Statistical Manual
of Mental Disorders, Third Edition (DSM-III)4, including an
atheoretical definition of mental disorders and diagnoses based on
polythetical operational criteria, have led to an impoverishment
of the psychodynamic conception of the personality construct5.
The operationalizing definition of borderline personality disorder
in DSM, for example, is a too broadly sketched, over-inclusive
category that is not defined by psychodynamic concepts, such as
intrapsychic conflict, defense mechanisms, psychological deficits,
object relations, transference, and countertransference6. Thus,
the arbitrary categorization promoted by the DSM produces a
heterogeneous diagnostic entity that is relatively uninformative
for understanding the psychodynamic concepts of personality
organization, especially in psychodynamic settings.
The consideration of personality on a psychodynamics basis
allows therapists to consider that a single behavior can serve
multiple functions depending on the underlying personality
structure2, allowing a more complex understanding of the individual
beyond phenomenological simplification. The understanding of
levels of normal, neurotic, borderline, and psychotic personality
organization continues to allow a more comprehensive view of the

Address for correspondence: Rochelle Marquetto, MD, Av. Ipiranga, 6690, Sexto Andar, Unidade de Internação Psiquiátrica do Hospital São Lucas da PUCRS. CEP: 90619-900, Porto Alegre, RS, Brazil.
Tel: 55-51-982233520; E-mail: drarochellemarquetto@gmail.com
46 Hessel CR / Arch Clin Psychiatry. 2021;48(1): 45-50
intrapsychic conflicts, defensive operations, integrity of identity,
and internalized value system, which has causal implications in
the processes of affective regulation, impulse control, and object
relations, as well as fundamental concepts of psychodynamics and
those related to the phenotypic expression of psychopathology. As
a result, treatments that alter psychological structures and mental
organizations can be used to identify specific pathological features
of underlying psychological structures2.
Although the evaluation of personality organization has
traditionally been performed clinically, through an experienced
psychodynamic therapist, alternative methods have been developed
to make large-scale studies feasible and to facilitate the validation
process of the construct. One of the methods employed is the use
of self-reporting questionnaires, developed in a way that facilitates
the collection of information and quickly reports on various
psychodynamic characteristics of the individual, without the need
for an in-depth interview. The Inventory of Personality Organization
(IPO) is the questionnaire most extensively used to capture
Kernberg's organizational levels7. The IPO has been used in several
studies about personality organization and psychopathology8–12,
including changes in psychotherapy13, showing to be a valid and
reliable instrument14–17. The IPO was also found to be a reliable
measure of the severity of personality functioning, as well as the
features connected to personality functioning, as intended by
DSM–518.
New diagnostic systems for personality disorders based on
dimensional approaches as presented in DSM-519 and ICD-1120
have established the core of personality pathology by the level of
impairment of personality functioning. The alternative model for
personality disorders (AMPD) printed in Section III of DSM-
5 has as its first criterion (Criterion A) the identification of the
level of impairment of personality functioning. People identified
with moderate or severe impairment in two21 out of four domains
(identity, self-direction, empathy, and intimacy) are likely to
present a personality pathology. The dimensional model underlying
criterion A was established based on a review of theoretical models
and scientific research that determined the main predictors of
personality pathology22. Kernberg's model was included in this
review, and empirical researches have demonstrated its association
with criterion A23–29. Concerning ICD-11, the new diagnostic
system also presents a dimensional approach in which the
personality pathology is graded in a continuum ranging from an
adaptive personality functioning to severe personality pathology20.
This model is theoretically close to AMPD’s criterion A30 and also
close to Kernberg’s model31.
One indication of the concurrent validity of the IPO was its
concordance with the severity of personality disorders, suggesting
that the IPO reflects personality pathology in accordance with
the DSM framework in general, more than specific categories of
DSM personality disorders18. The IPO total score also presented
a statistically significant correlation with the ICD-11 personality
severity score31 as operationalized by the Standardized Assessment
of Severity of Personality Disorder SASPD32. These findings
highlight the IPO's clinical utility and its relevance to the personality
pathology field.
Originally designed to assess three factors (identity diffusion,
primitive defenses, and reality testing impairments), more recently,
the IPO’s tripartite latent structure was questioned, and a new
4-factor measurement model was replicated in some studies,
with factors representing instability of self and others, instability
of goals, instability of behavior, and psychosis33–35. This new IPO
factorial structure that was empirically established is theoretically
aligned to the severity of personality functioning as described in
both diagnostic systems (i.e. AMPD and ICD-11). The personality
structure, as measured by the IPO, is a dimensional construct,
varying from normal to pathological valences. Thus, IPO has been
used to differentiate clinical of non-clinical samples, with both Axis
I and personality disorders34,36. However, IPO is also associated
with negative affect in non-clinical samples14, such as depressive
and anxiety states, which is consistent with the Kernberg proposal2,
which associates problems related to the difficulties of integrating
the concept of self with difficulties of the individual to contact
with social and interpersonal demands, making the individual
vulnerable to negative emotional states. In this way, theoretically,
IPO could discriminate groups with different levels of structural
personality severity, even among non-clinical groups, identifying
individuals more vulnerable to distress symptoms.
Although the IPO has been shown to be a clinically useful
tool for identifying psychopathology and measuring personality
functioning, studies conducted considering its 4-factor structure
have recruited only non-clinical samples33 or mixed clinical samples
(only outpatients in heterogeneous settings; or both outpatients and
inpatients, with mixed features and settings)34,35. Thus, here we aim
to compare levels of personality organization using the 4-factor
structure of the IPO between a non-clinical functional sample and a
clinical sample with an indicator of the severity of psychopathology
(psychiatric inpatients). We hypothesized that the IPO factors
would differentiate levels of severity by discriminating non-clinical
groups with different levels of psychopathology (using a measure of
distress) from a group with severe psychopathology.
Methods
Sample and design
This was a transversal observation study. The clinical sample was
recruited from a psychiatric ward of a general hospital [Hospital
São Lucas da Pontifícia Universidade Católica do Rio Grande do
Sul (PUCRS), Porto Alegre, Brazil]. This ward has 21 beds and
admits patients mainly for mood and personality disorders, as
well as suicide attempts and suicidal ideation37. Inpatients were
recruited by convenience from March 2015 to April 2017, and
systematically between May and August 2017. Adult patients who
were able to read and understand the instruments and did not
present impaired critical judgment or severe residual symptoms
at the time of recruitment were invited to complete a self-report
questionnaire about personality structure. At the end of these
periods, 126 inpatients were recruited.
The non-clinical sample was selected by convenience among
medical and nursing students from PUCRS, of ≥ 18-years-old,
between August and October of 2016. The choice for this sample
for the non-clinical group was based on their good functional
degree (active undergraduate students). The participants were
similar to the main profile of individuals used in validation studies
of the IPO15,17,33,38. However, this population has been identified as
having a high prevalence of psychopathology, with a prevalence
of depression up to 3-times higher than in the community
population39. One-hundred-ninety-seven medical students and
80 nursing students were invited to participate. The students who
accepted to participate in the study received the socio-demographic
questionnaire and self-reports instruments of psychopathology and
personality.
Instruments
Sociodemographic questionnaire (SD)
This is a self-reported questionnaire with sociodemographic and
clinical data, such as gender, age, marital status, and data about
medical history. For the clinical sample, in addition to the above
data, medical records were collected on the psychiatric diagnosis
 Hessel CR / Arch Clin Psychiatry. 2021;48(1): 45-50
according to the International Classification of Diseases (ICD-10).
Inventory of Personality Organization – Brazilian version (IPO-Br)
To measure the level of personality organization, we used the
Brazilian version of Inventory of Personality Organization (IPO-
Br). The IPO-Br is an 83-item self-report questionnaire that was
linguistically and culturally adapted, being adjusted to the Brazilian
socio-cultural reality and maintaining equivalence with the original
version40. The IPO-Br had its psychometric proprieties tested
and validated for the Brazilian population in its 4-factor model,
nominees Instability of Self and Other (ISO), Instability of Goals
(IG), Instability of Behaviors (IB), and Psychosis (PSY). The IPO-
Br also includes three additional scales, with the dimensions Self-
Directed Aggression (SDA), Distortion of Moral Values (DMV),
and Sadistic Aggression (SA)41. The IPO-Br presents good internal
consistency, with alpha coefficients of 0.94 (ISO), 0.90 (IB), 0.86
(IG), 0.84 (PSI), 0.70 (SDA), 0.74 (DMV), and 0.80 (SA). Their
normative values according to sex and age group are preliminarily
available for the Brazilian population35. The IPO-Br was applied
for both clinical and non-clinical samples, and their scores were
calculated according to the recommendations of the Brazilian
validation study.
Patient Health Questionnaire (PHQ-4)
To categorize the non-clinical sample into levels of psychopathology,
we used a general measure of distress. PHQ-4 is a reduced
version of the self-report PHQ questionnaire with two questions
of the PHQ-9 (part of the instrument that measures depression)
and two questions of the GAD-7 (an instrument that measures
anxiety and was incorporated to the PHQ), acting as an ultra-brief
depression and anxiety (distress) screening42. The instrument has
a polytomy Likert type scale, where the subject scores his anxious
and depressive symptoms in the 2 weeks prior to the test, with the
range varying from 0 (not once) to 3 (almost every day). The PHQ-
4 total score ranges from 0 to 12, with categories of psychological
distress being none (0–2), mild (3–5), moderate (6–8), and severe
(9–12). According to these thresholds, the non-clinical sample
was categorized into four groups, ranging from "no symptoms"
to "severe symptoms" of distress. In our sample, the instrument
showed proper reliability, with Cronbach Alpha of 0.73 for the
general scale, and 0.75 and 0.72 respectively for the depression and
anxiety scales.
Procedures and final sample
In the clinical sample, inpatients answered the questionnaires in the
days before discharge when they presented significant improvement
of the acute psychopathology, and the severity of the symptoms
improved sufficiently to be discharged. The patients who agreed
to participate received the questionnaires (socio-demographic and
IPO-Br). Individuals who did not agree to participate in the study,
with psychotic symptoms at discharge or with intellectual deficit
were excluded from the study. We exceptionally included in the final
sample an individual under the age of 18, who was admitted to the
adult unit and had the maturity to participate and respond to the
instruments. The individuals with more than 10% of unanswered
items in each factor were also excluded. The final sample was 56
patients with a full version of the instrument. The mean [± standard
deviation (SD)] age was 37.3 ± 14.86 years [range: 16–66 years];
18 participants were male (32.1%), and 38 were female (67.9%).
The clinical diagnosis was performed by the assistant psychiatrist
according to the International Classification of Disease 10th version
(ICD-10).
In the non-clinical sample, the subjects were invited to participate in
the study during the class period, answering a pen-paper version of
47
the instruments in the classroom. Sixty-two students did not return
the instruments. The final sample consisted of 214 questionnaires
(159 medical students and 54 nursing students). The mean age was
23.6 ± 4.21 years (range: 19–43 years); 65 participants were male
(30.5%), and 147 were female (69.0%; data on gender was missing
for 1 participant).
Statistics
Descriptive statistics were used for characterization of the sample,
analyzed by absolute number, percentages, mean and standard-
deviation. To evaluate the internal consistency of IPO-Br, the
Cronbach’s alpha method was calculated for all subscales. To
calculate differences between the mean level of IPO-Br factors
between groups, we performed analysis of variance controlling
for participants’ age (ANCOVA), and the post-hoc differences
were evaluated by the Bonferroni test. The significance level was
considered as p < 0.05. All analyses were conducted by the SPSS®
Statistics 23.0 (IBM®, Chicago, IL, USA).
Ethics
None of the procedures presented risks to the participants.
Participants were informed that participation in the study did not
influence their academic performance evaluation (non-clinical
sample) or their treatment (clinical sample). Identifications were
omitted, and the data were kept confidential. This study was
approved by the Research Ethics Committee at the Pontifícia
Universidade Católica do Rio Grande do Sul (protocol number:
68823717.3.0000.5336).
Results
The final sample consisted of 269 individuals, 214 of the non-clinical
sample and 56 inpatients. According to the PHQ-4, the non-clinical
sample was categorized into four groups: no symptoms (32.9%),
mild distress symptoms (39.9%), moderate distress symptoms
(20.2%), and severe distress symptoms (8%). In the clinical sample,
the main diagnoses were unipolar depression (38.2%), bipolar
disorder (16.4%), and substance-related disorders (16.4%). The
descriptive values of the sociodemographic and clinical data are
presented in Table 1.
Table 2 shows the mean values of the IPO-Br factors in the
four main scales and the three secondary scales for the five groups.
Analysis of variance controlling for participants’ age (ANCOVA)
indicated a general trend that the inpatients' group had higher
mean scores than the non-clinical groups. The factor with the
greatest discriminative power was the ISO, where the samples with
few distress symptoms consistently differed from those with severe
symptoms and inpatients. In the Table 2, the reliability coefficients
are presented by Cronbach’s alpha method. All four primary IPO-
Br scales presented adequate reliability values ranging from 0.87
(PSY) to 0.93 (ISO). For the additional scales, two factors presented
alpha values lower than 0.70. SDA and SA each presented an alpha
of 0.65, while DVM presented an alpha of 0.76.
Discussion
This study aimed to investigate whether the IPO-Br factors
would be able to discriminate different people grouped by their
levels of psychopathology. We found that individuals with severe
psychopathology (inpatients) had significantly higher scores on
personality structure dysfunction than individuals from a non-
clinical sample with different levels of symptoms. The ISO factor
was the only factor that discriminated individuals in the non-
clinical sample. The present study shows an important finding
48 Hessel CR / Arch Clin Psychiatry. 2021;48(1): 45-50

Table 1: Descriptive statistics of non-clinical (undergraduates) and clinical (inpatients) samples.

Total Non-Clinical Inpatients p-value
n=269 n=213 n=56
Gender (% Female) 69.0% 69,3% 67.9% .831
Age - M ± SD 26.4 ± 9.52 23.6 ± 4.21 37.3 ± 14.8 <0.001
Marital Status

Single 86.3% 91.1% 65.3% <0.001

Married/live together 10.7% 8.5 20.4%

Separated/divorced 3.1% .5% 14.3%

Higher Education (%) 97% 100% 85.7% <0.001
Psychiatric diagnosis (%)
Unipolar depression - - 38.2% -
Bipolar disorder - - 16.4% -
Use/misuse disorders - - 16.4% -
Neurotic/anxious disorders - - 10.9% -
Personality disorders - - 10.9% -
Psychotic disorders - - 7.3% -
PHQ-4 – M ± SD - 4.10 ± 2.74 - -
PHQ-4 categories (%)
No distress symptoms - 32.9% - -
Mild distress symptoms - 39.0% - -
Moderate distress symptoms - 20.2% - -
Severe distress symptoms - 8.0% - -

Table 2: Comparison of mean scores of IPO-Br factors controlling for age between groups with no symptoms of psychological distress [A], mild [B], moderate [C], severe [D]
and inpatients [E], and Cronbach’s alpha values.
α Total No distress [A] Mild [B] Moderate [C] Severe [D] Inpatients [E] p-value Post hoc differences
n = 269 n = 71 n = 82 n = 43 n = 17 n = 56 (Bonferroni)
M ± SD M ± SD M ± SD M ± SD M ± SD M ± SD

Instability of self/other .94 2.09 0.74 1.72 0.54 1.89 0.57 2.02 0.54 2.41 0.87 2.82 0.74 < .001 AB < DE | C < E
Instability of goals .90 1.92 1.13 1.58 0.84 1.74 0.88 1.77 1.15 1.82 1.03 2.75 1.39 < .001 ABCD < E

Psychosis .87 1.38 0.59 1.16 0.21 1.20 0.25 1.31 0.42 1.38 0.57 1.96 0.94 < .001 ABCD < E

Instability of behavior .89 1.77 0.71 1.47 0.46 1.59 0.52 1.69 0.55 1.71 0.44 2.50 0.87 < .001 ABCD < E
Self-directed aggression .66 1.41 0.48 1.21 0.21 1.30 0.32 1.36 0.37 1.43 0.44 1.87 0.70 < .001 ABCD < E

Distortion of moral values .77 1.84 0.60 1.60 0.47 1.72 0.52 1.78 0.47 1.86 0.45 2.34 0.70 < .001 ABCD < E

Sadistic aggression .65 1.19 0.36 1.12 0.18 1.16 0.31 1.09 0.16 1.19 0.32 1.39 0.57 < .001 ABC < E

Note. Mean and standard-deviation values displayed are unadjusted.

on the informative value of personality structure assessment in
individuals with symptoms of psychopathology. To our knowledge,
this is the first study were the IPO was used to differentiate groups
with different levels of psychopathology symptoms, regardless of a
formal psychiatric diagnosis.
The evaluation of personality structure by IPO has been
performed in several studies comparing individuals with and
without personality disorders, individuals with personality
disorders and other psychopathologies, and with different
psychopathological symptoms9,10,12,14,36, in clinical and non-clinical
samples. However, its initial tripartite structure, which has separate
discrete subscales for identity diffusion, primitive defenses, and
reality testing, has not been replicated in studies with exploratory
structural equation modeling (ESEM) strategies33,35. Instead, a
four-factor model has been replicated, which represents the more
complex structure of Kernberg’s personality organization model.
Like other studies, we also found important differences in these
factors when comparing individuals with different severities of
psychopathology and mental health indicators, mainly with the
factor ISO33–35. Thus, undergraduate students with no and minor
distress symptoms obtained lower average scores in the ISO factor
than students with severe distress symptoms. Since the impaired
sense of self and a lack of integration of the concept of significant
others interferes with the capacity for realistic assessment of others,
this factor might be more sensitive to capture operating nuances
related to distress symptoms2. These symptoms might be the
 Hessel CR / Arch Clin Psychiatry. 2021;48(1): 45-50
product of the difficulties of predicting actions, and difficulties in
social interactions, commitments, and personal interests related
to a not well-integrated sense of self, which are relativized but not
absent even in situations of higher levels of functioning, such as the
academic ambiance of medical and nursing courses. The ISO factor
is also the factor that is most strongly associated with both positive
and negative mental health indicators and is the largest supplier of
the information level within latent personality traits35.
Since the level of personality organization is an important
indicator of its functioning and is related to vulnerability to
psychiatric disorders, our findings reinforce that the constructs
evaluated by the IPO are indicators of pathological personality
organization35. All scales presented great differences between
clinical and non-clinical samples. The IPO scores have been
strongly associated with measures of depression and anxiety14,18,
and this is consistent with the Kernberg BPO construct-model14.
Among the tested factors, ISO, IB, and SDA scored highest, with
averages for inpatients above 1.5 SDs from the normative values.
Since most of the inpatients had a diagnosis of mood disorders,
and suicide behavior being one of the most important morbidities
for admission, the SDA scores might represent the self-aggressive
component, which in its pathological pole has suicide as an
expression. PSY was the main factor with a lower average in all
samples, presenting higher values for inpatients, although not as
high as the other factors. This might be due to the low percentage of
psychotic individuals in the clinical sample.
The results we got can also underscore the similarity between
Kernberg's model and the AMPD. Since the criterion A of
the AMPD is represented by disturbances in individual and
interpersonal functioning, constituting the core of personality
psychopathology43, IPO constructs are relevant and useful for
understanding and managing personality disorders from a DSM-
5 AMPD perspective44. Lowyck et al. found that IPO was a valid
measure to differentiate levels of personality functioning in a
sample of patients with personality disorders18 and the current
study indicates IPO’s ability to differentiate levels of personality
functioning across people with different levels of psychological
distress, including those with severe symptoms that require
hospitalization.
The present study has some limitations that might have a
potential impact on our findings. First, the nonclinical sample
was composed of young undergraduate students and selected by
convenience. This sample presents several differences in relation
to the inpatient sample. However, as already mentioned, this
population is similar to that most found in the validation studies
of the instrument. Moreover, to minimize age bias, we controlled
its effect in the analysis of variance. The scores of the nonclinical
sample were very similar to the means of the normative sample,
especially in the individuals without psychopathology, which
reinforces that our comparative sample was adequate. Second, we
do not use standardized instruments for the diagnostic evaluation
of inpatients. However, as our goal was to compare severity levels
of psychopathology rather than diagnostic groups, we believe
that this limitation did not detract from our findings. Third, the
sample size was small, especially in the clinical sample. Despite this,
the differences found in relation to the non-clinical sample were
significantly high, which might also show that the instrument was
answered coherently by the included individuals. Fourth, although
not specific to this study, it concerns to the use of self-reports in
operationalizing Kernberg’s model because it is not optimally suited
for the assessment of intrapsychic patterns. In this way, it is worthy
to mention the measurement model designed to assess personality
structure according to Kernberg's model based on a structured
interview45. Finally, other limitation is the length of the IPO which
49
is a relatively long instrument (83 items) concerning the amount of
information it provides. It is suggested to refine the measure to be
brief once clinical work is often limited by time.
In summary, the present study suggests that the IPO-Br
is a useful instrument to assess personality pathologies and
personality functioning in individuals with different level of
psychopathology. Our findings show that subjects with severe
levels of psychopathology, represented by psychiatric inpatients,
have higher personality structure dysfunction than a non-clinical
sample. Whereas deeper personality structures should not be
evaluated only by observational criteria, and are only inferred by
observed characteristics, this instrument might be a useful auxiliary
tool for the evaluation of personality functioning in hospitalized
patients. Once the patient's personality organization is understood,
it could potentially aid in predicting some future pathology and
perhaps risk assessments, thereby helping to plan treatments for a
better prognosis. However, more research concerning the validity
of these measures to assess levels of personality functioning in
severe psychiatric patients is needed to confirm our results.
References
1. Kernberg OF. What Is Personality? Journal of Personality Disorders.
2016;30:145–156.
2. Kernberg OF, Caligor E. A Psychoanalytic Theory of Personality
Disorders. in Major Theories of Personality Disorder 481. The Guilford
Press, 2005.
3. Kernberg O. Aggressivity, Narcissism, and Self-Destructiveness
in the Psychoterapeutic Relationship: New Developments in the
Psychopathology and Psychotherapy of Severe Personality Disorders.
Yale University Press, 2004.
4. American Psychiatric Association. DSM-III. Diagnostic and Statistical
Manual of Mental Disorders (Third Edition). (American Psychiatric
Association., 1980).
5. Aronson TA. Historical perspectives on the borderline concept: a review
and critique. Psychiatry. 1985;48:209–222.
6. Waldinger RJ. The role of psychodynamic concepts in the diagnosis of
borderline personality disorder. Harv Rev Psychiatry. 1993;1:158–167.
7. Clarkin JF, Kernberg OF. Inventory of Personality Organization. (1995).
8. Hoermann S, Clarkin JF, Hull JW, Levy KN. The construct of effortful
control: an approach to borderline personality disorder heterogeneity.
Psychopathology. 2005;38:82–86.
9. Spitzer, C. et al. Borderline personality organization and dissociation.
Bull Menninger Clin. 2006;70:210–221.
10. Pincus AL, Ansell EB, Pimentel CA, Cain NM, Wright AGC, Levy
KN. Initial construction and validation of the Pathological Narcissism
Inventory. Psychol Assess. 2009;21(3):365-379.
11. Vermote R, Fonagy P, Vertommen H, Verhaest Y, Stroobants R,
Vandeneede B, et al. Outcome and outcome trajectories of personality
disordered patients during and after a psychoanalytic hospitalization-
based treatment. J Pers Disord. 2009;23(3):294-307.
12. Walter M, Berth H, Selinger J, Gerhard U, Küchenhoff J, Frommer J,
Dammann G. The lack of negative affects as an indicator for identity
disturbance in borderline personality disorder: a preliminary report.
Psychopathology. 2009;42(6):399-404.
13. Giesen-Bloo J, van Dyck R, Spinhoven P, van Tilburg W, Dirksen C, van
Asselt T, Kremers I, Nadort M, Arntz A. Outpatient psychotherapy for
borderline personality disorder: randomized trial of schema-focused
therapy vs transference-focused psychotherapy. Arch Gen Psychiatry.
2006 Jun;63(6):649-58.
14. Lenzenweger MF, Clarkin JF, Kernberg OF, Foelsch PA. The Inventory
of Personality Organization: psychometric properties, factorial
composition, and criterion relations with affect, aggressive dyscontrol,
psychosis proneness, and self-domains in a nonclinical sample. Psychol
Assess. 2001 Dec;13(4):577-91.
15. Igarashi H, Kikuchi H, Kano R, Mitoma H, Shono M, Hasui C, et al.
The Inventory of Personality Organisation: its psychometric properties
among student and clinical populations in Japan. Ann Gen Psychiatry.
2009;8:9.
50 Hessel CR / Arch Clin Psychiatry. 2021;48(1): 45-50
16. Verreault M, Sabourin S, Lussier Y, Normandin L, Clarkin JF. Assessment
of personality organization in couple relationships: factorial structure of
the inventory of personality organization and incremental validity over
neuroticism. J Pers Assess. 2013;95(1):85-95.
17. Barreto JF, Matias M, Carvalho HM, Matos PM. Uncovering personality
structure with the Inventory of Personality Organization: An exploration
of factor structure with a Portuguese sample. Revue Européenne
de Psychologie Appliquée/European Review of Applied Psychology
2017;67:247–257.
18. Lowyck B, Luyten P, Verhaest Y, Vandeneede B, Vermote R. Levels of
personality functioning and their association with clinical features and
interpersonal functioning in patients with personality disorders. J Pers
Disord. 2013;27(3):320-336.
19. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders (DSM-5®). American psychiatric publishing, 2013.
20. Bach B, First MB. Application of the ICD-11 classification of personality
disorders. BMC psychiatry. 2018;18: 351.
21. Morey LC, Skodol AE. Convergence between DSM-IV-TR and DSM-5
diagnostic models for personality disorder: Evaluation of strategies for
establishing diagnostic thresholds. J Psychiatr Pract. 2013;19(3):179-93.
22. Bender DS, Morey LC, Skodol AE. Toward a model for assessing level
of personality functioning in DSM-5, part I: A review of theory and
methods. Journal of Personality Assessment. 2011;93:332–346.
23. Esguevillas Á, Díaz-Caneja CM, Arango C, Rey-Mejías ÁLD, Bernardo
EG, Delgado C, et al. Personality organization and its association with
clinical and functional features in borderline personality disorder.
Psychiatry Res. 2018;262:393-399.
24. Ferrer M, Andión Ó, Calvo N, Hörz S, Fischer-Kern M, Kapusta ND,
et al. Clinical Components of Borderline Personality Disorder and
Personality Functioning. Psychopathology. 2018;51(1):57-64.
25. Baus N, Fischer-Kern M, Naderer A, Klein J, Doering S, Pastner B,
Leithner-Dziubas K, Plener PL, Kapusta ND. Personality organization
in borderline patients with a history of suicide attempts. Psychiatry Res.
2014;218(1-2):129-33.
26. Fischer-Kern M, Buchheim AH, Susanne S, Doering P, Kapusta S, Nestor
D. et al. The relationship between personality organization, reflective
functioning, and psychiatric classification in borderline personality
disorder. Psychoanalytic Psychology 2010;27(4):395.
27. Hörz-Sagstetter S, Caligor E, Preti E, Stern BL, De Panfilis C, Clarkin
JF. Clinician-Guided Assessment of Personality Using the Structural
Interview and the Structured Interview of Personality Organization
(STIPO). J Pers Assess. 2018;100(1):30-42.
28. Preti E, Di Pierro R, Costantini G, Benzi IMA, De Panfilis C, Madeddu
F. Using the Structured Interview of Personality Organization for DSM-
5 Level of Personality Functioning Rating Performed by Inexperienced
Raters. J Pers Assess. 2018;100(6):621-629.
29. Kampe L, Zimmermann J, Bender D, Caligor E, Borowski AL, Ehrenthal
JC, et al. Comparison of the Structured DSM-5 Clinical Interview for the
Level of Personality Functioning Scale With the Structured Interview of
Personality Organization. J Pers Assess. 2018;100(6):642-649.
30. \Bach B, Anderson JL. Patient-Reported ICD-11 Personality Disorder
Severity and DSM-5 Level of Personality Functioning. J Pers Disord.
2020;34(2):231-249.
31. Oltmanns JR, Widiger TA. Evaluating the assessment of the ICD-11
personality disorder diagnostic system. Psychol Assess. 2019;31(5):674-
684.
32. Olajide K, Munjiza J, Moran P, O'Connell L, Newton-Howes G, Bassett
P, et al. Development and Psychometric Properties of the Standardized
Assessment of Severity of Personality Disorder (SASPD). J Pers Disord.
2018;32(1):44-56.
33. Ellison WD, Levy KN. Factor structure of the primary scales of
the Inventory of Personality Organization in a nonclinical sample
using exploratory structural equation modeling. Psychol Assess.
2012;24(2):503-517.
34. Preti E, Prunas A, De Panfilis C, Marchesi C, Madeddu F, Clarkin JF.
The facets of identity: personality pathology assessment through the
Inventory of Personality Organization. Personal Disord. 2015;6(2):129-
140
35. Oliveira SE da S. Structural and Dimensional Personality Assessment:
Psychometric and Clinical Application Studies [Avaliação Estrutural e
Dimensional da Personalidade: Estudos Psicométricos e de Aplicação
Clínica]. (Universidade Federal do Rio Grande do Sul: Porto Alegre,
2016).
36. Smits DJM, Vermote R, Claes L, Vertommen H. The Inventory of
Personality Organization–Revised. European Journal of Psychological
Assessment. 2009;25:223–230.
37. Pavan G, Godoy JA, Monteiro RT, Moreschi HK, Nogueira El,
Spanemberg SL. Is there a correlation between physicians’ clinical
impressions and patients’ perceptions of change? Use of the Perceived
Change Scale with inpatients with mental disorders. Trends Psychiatry
Psychother. 2016;38:234–241.
38. Dagnall N, Denovan A, Parker A, Drinkwater K, Walsh RS. Confirmatory
Factor Analysis of the Inventory of Personality Organization-Reality
Testing Subscale. Front Psychol. 2018;9:1116.
39. Rotenstein LS, Ramos MA, Torre M, Segal JB, Peluso MJ, Guille C, et al.
Prevalence of Depression, Depressive Symptoms, and Suicidal Ideation
Among Medical Students: A Systematic Review and Meta-Analysis.
JAMA. 2016;316(21):2214-2236.
40. Oliveira SES, Bandeira DR. Linguistic and cultural adaptation of the
Inventory of Personality Organization (IPO) for the Brazilian culture.
Journal of Depression and Anxiety. 2011;1:105.
41. Silveira LB, Oliveira SES, Bandeira DR. Validity Evidences of the
Inventory of Personality Organization-Brasil (IPO-Br): Its Relation
with the Five-Factor Model of Personality. Trends in Psychology.
2018;26:1891–1905.
42. Spitzer RL, Williams JBW, Kroenke K. Instruction Manual: Instructions
for Patient Health Questionnaire (PHQ) and GAD-7 Measures. (2017).
43. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders (DSM-5®). (American Psychiatric Pub, 2013).
44. Hutsebaut J, Kamphuis JH, Feenstra DJ, Weekers LC, De Saeger
H. Assessing DSM-5-oriented level of personality functioning:
Development and psychometric evaluation of the Semi-Structured
Interview for Personality Functioning DSM-5 (STiP-5.1). Personal
Disord. 2017;8(1):94-101.
45. Stern BL, Caligor E, Clarkin JF, Critchfield KL, Horz S, MacCornack
V, et al. Structured Interview of Personality Organization (STIPO):
preliminary psychometrics in a clinical sample. J Pers Assess.
2010;92(1):35-44.
 Original article

Factors influencing self-esteem in Tunisian adolescents with prosocial behavior

Charfi Nada1

Kammoun Wiem2
https://orcid.org/0000-0002-5809-4551
Maâlej Bouali Manel1

Omri Sana1

Feki Rim1

Smaoui Najeh1

Zouari Lobna1

Moalla Yosr2

Ben Thabet Jihene1

Maâlej Mohamed1

Psychiatry C Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
1

Child Psychiatry Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
2

Received: 12-01-2020 – Accepted: 17-11-2020

DOI: 10.1590/0101-60830000000278

ABSTRACT
Background and aim: Previous research has shown some varying results of the link between prosocial behavior and self-esteem among
adolescents. However, there is a dearth of studies considering the external factors’ impact on self-esteem among those adolescents. Thus,
this study aimed to assess self-esteem among a group of adolescents with prosocial behavior in the city of Sfax and to investigate whether
their self-esteem would be influenced by individual and familial factors. Methods: We led a transversal study, including 90 adolescents aged
14-20 years and members of voluntary association in Sfax (Tunisia). Self-esteem was measured by Coopersmith self-esteem inventory (SEI).
Results: The mean age was 16.59 years with a sex ratio of 0.87 (53.3% female). All the participants were schooled and 30% of them attended
high schools. 71.1% were from high-income families and 78.9% of them lived in two-parent families. A rate of 58.9% of adolescents had a
high total self-esteem score mainly in the familial and in the social subscales. High total self-esteem was significantly associated with a high
parental educational level (p=0.001), a harmonious relationship with parents (p=0.020) and participation in decision-making processes
within the family (p=0.009). The academic average was significantly higher in adolescents with high total self-esteem (p=0.001). Conclusion:
This study highlighted the role of structural factors such as family’s income and interpersonal relationships and emphasized the crucial role
of academic success as predictable indicators of high self-esteem.

Nada C / Arch Clin Psychiatry. 2021;48(1):51-56

Keywords: adolescents, proscocial behavior, self-esteem, Coopersmith self-esteem inventory

Introduction An important predictor of acceptance among peers is prosocial

Adolescence is a period of transition during which teens gradually
move away from the protection of their families and turn more to
their peers for support and company. Hence, poor interpersonal
relationships and perceived lack of social support in adolescence
are associated with a perception of poor psychosocial well-being
and poor quality of daily life, and with a high risk of developing
anxiety and depression1. On the other hand, social acceptance
increases self-esteem and well-being.
behavior, which is defined as any act with the goal of benefiting
another person2. In fact, adolescents who show more prosocial
behavior are more likely to be accepted by peers than adolescents
who show less prosocial behavior3. A large amount of empirical
research has documented the beneficial role of prosocial behavior
for the actor, as well as for the target, as it is associated with
better peer relationships4, higher levels of self-esteem5, and civic
engagement during the transition from adolescence to young
adulthood6.

Address for correspondence: Kammoun Wiem, Child Psychiatry department, Hedi Chaker university hospital, Sfax, TUNISIA, phone number: +216 58 373 722, e-mail: wiem.
kamoun@gmail.com
ORCID ID: 0000-0002-5809-4551
52 Nada C / Arch Clin Psychiatry. 2021;48(1): 51-56
From another perspective, self-esteem is one of the main
predictors of psychological well-being, and acquiring an adequate
level of self-esteem is crucial to adolescent development7. Self-
esteem is indeed an affective dimension of personal identity, which
represents an essential component of self-image. It represents the
set of feelings and attitudes that a person experiences with respect
to himself, and which guide his spontaneous reactions. It also steers
a person’s aspirations and influences the project design strategies
through past successes and failures8.
Prosocial behavior might be associated with self-esteem not
only during adolescence but also over the long term. In this regard,
empirical evidence has shown that the direct effect of pro-sociality
on self-esteem was statistically significant during the transition
from middle adolescence to young adulthood5. In addition to direct
evidence, gratitude and acknowledgment often associated with
prosocial behavior may promote self-worth and provide a means
for bolstering feelings about oneself. In this way, prosocial behavior
may foster self-worth and more global self-esteem9.
In sum, previous research has shown some varying results
of the link between prosocial behavior and self-esteem among
adolescents. However, there is a dearth of studies considering the
external factors’ impact on self-esteem among those adolescents.
The objectives of this study were to assess self-esteem among
a group of adolescents with prosocial behavior in the city of Sfax
and to investigate whether self-esteem would be influenced by
individual factors and familial factors of those adolescents.
Methods
Sample and study design
We led a transversal, descriptive and analytical study, over four
months, from June until September 2018, based on a survey of
a group of 90 adolescents. These adolescents were members of
Interact clubs in Sfax (Tunisia) drawn from different Colleges and
high schools.
Interact clubs are service clubs for youth ages 12 to 18,
sponsored by Rotary International. Being a member of an Interact
club gives the opportunity to participate in meaningful service
projects and develop leadership skills, understand the importance
of responsibility and promote international awareness. It also offers
the chance to learn the importance of serving others, showing
respect and developing personal integrity.
The average age of the participants was 16.59 ± 1.45 years
(range: 13 to 20). The sample was female-dominated (53.3% of
cases) with a sex ratio of 0.87. The survey was conducted through
face-to-face interview, undertaken by a single interviewer with
informed consent of the adolescent and upon prior consent of the
Interact club president.
Instruments
These interviews followed a predetermined format, and identified
apart for the socio-demographic information concerning the living
conditions (mono or biparental family), family circumstances
(family income, parents’ educational level, parenting style,
relationship with parents, communication with parents), schooling
(academic attainment, academic average, extracurricular activities),
and relational elements (decision making participation, friendship
network).
Self-esteem was measured by Coopersmith self-esteem
inventory (SEI)10. The Coopersmith SEI is a 58-item self-report
instrument to which each subject responds by using “like me” or
“unlike me”. The present study was conducted with the Arabic
translation of the Coopersmith SEI, in its school form for the ages
8-15. The Coopersmith SEI was developed through research to
assess attitude toward oneself in general, and in specific contexts.
This form yields a total score and separate scores for four subscales
designed to assess perception of self (General Self-esteem: 26
items), peers (Social Self-esteem: 8 items), parents (familial self-
esteem: 8 items), and school (School self-esteem: 8 items). A score
higher than 18.64 in general self-esteem subscale, 5.67 in social self-
estime subscale, 4.92 in familial self-esteem subscale, 4.12 in school
self-esteem subscale and 33.35 in total score indicates a positive
self-esteem10.
Compared with other instruments assessing self-esteem, the
Coopersmith SEI seems to be well researched, well documented,
and widely used. It is brief and easily scored. It is reliable and stable,
and there is an adequate amount of information about its validity11.
Statistics
The statistical analysis was performed by using the SPSS statistical
package, version 20. The Chi-square test and the Fisher test were
used to compare frequencies, and the Student test to compare means.
p values less than 0.05 were considered statistically significant.
Results
Sample identification
The sample consisted of 90 adolescents, recruited over a period of
four months (June to September 2018). The sex ratio (male/female)
was 0.87 with female domination (53.3%). All of these adolescents
were schooled and 30% of them attended high schools. Half of
them had an academic average of 13 to 15out of 20in the 2017-2018
school year, and 72.1% of them were involved in extracurricular
activities (sport in 50% of cases). As for the parents, 66.7% of the
fathers and 61.1% of the mothers had a university degree. More
than two thirds of the adolescents (71.1%) were from high-income
families. The adolescents lived in two-parent families in 78.9% of
cases.
Self-esteem assessment
A rate of 58.9%of adolescents had a high total self-esteem score
mainly in the familial subscale (54.4%) and in the social subscale
(51.1%) (Figure 1).
Mean scores of self-esteem according to the different subscales
are represented in table 1 (Table 1).
Relationship between self-esteem and socio-biographic
factors
To determine factors associated with self-esteem, we compared the
group of adolescents with high self-esteem to that of adolescents
with low self-esteem. The total self-esteem of adolescents was
independent of their sex, their perception of the parenting style
and their friendship network. Adolescents with high total self-
esteem were significantly more likely to have a high socioeconomic
level, a high parental educational level, a harmonious relationship
and satisfactory communication with parents, a participation
in decision-making processes within the family, and an
extracurricular activity. The academic average (2017-2018 school
year) was significantly higher in adolescents with high total self-
esteem (Table 2).
Discussion
In the present study, Self-esteem was measured by Coopersmith
SEI. This author defines self-esteem as an expression of approval
or disapproval toward oneself, representing a sign of the extent
to which an individual feels capable, effective and important10.
According to this inventory, almost 60% of the participants had a
high total self-esteem, particularly in familial (54.4%) and social
 Nada C / Arch Clin Psychiatry. 2021;48(1): 51-56 53

70%

58.9%
60%
54.4%
51.1%
50%
44.4%

40% 35.6%

30%

20%

10%

0%
general subscale school subscale social subscale familial subscale total

Figure 1: Distribution of adolescents having a high self-esteem according to the different subscales

Table 1: Distribution of mean scores of self-esteem according to the different subscales

Minimum Maximum Mean± SD†
General self-esteem 4 24 16.66±3.96
School self-esteem 2 7 4.27±1.61
Social self-esteem 1 7 5.41±1.29
Familial self-esteem 1 8 4.71±1.64
Total self-esteem 15 49 34.62±7.14
†SD: standard deviation

Table 2: Total self-esteem variation according to socio-biographic factors

Total SE† p Value
High Low
Sex
Male 54.8% 45.2% 0.450
Female 62.5% 37.5%
Family income
Low to medium 15.4% 84.6% <0.001
High 76.6% 23.4%
Father’s educational level
Illiterate/primary school 15.4% 84.6% 0.001
Secondary school/university 66.2% 33.8%
Mother’s educational level
Illiterate/primary school 0% 100% <0.001
Secondary school/university 68.8% 31.2%
Parenting style
Democratic 69.2% 30.8%
0.110
Authoritarian 45.5% 54.5%
Permissive 50% 50%
Relationship with parents
Harmonious 69% 31% 0.020
Conflictual 43.3% 56.7%
Communication with parents
Satisfactory 67.1% 32.9% 0.009
Almost non-existing 33.3% 66.7%
Decision-making
Yes 67.1% 32.9% 0.009
No 33.3% 66.7%
Friendship network
Good 65.2% 34.8% 0.100
Few or no friends 45.5% 54.5%
Academic average (2017-2018) 14.83±1.62 12.36±3.91 0.001
Extracurricular activity
Yes 73.2% 26.8% 0.010
No 46.9% 53.1%
54 Nada C / Arch Clin Psychiatry. 2021;48(1): 51-56
(51.1%) subscales. Furthermore, the mean score of social self-
esteem was higher than the mean scores of both familial and social
self-esteem subscales (5.41 versus 4.71 and versus 4.27, respectively).
As members of voluntary association, these adolescents
were engaged in positive and caring social behaviors, thus,
contributing to their own development and ensuring positive social
relationships. The links established between adolescents through
prosocial activities could enhance their active participation in the
community and provide an incentive to collaborate with adults.
These activities also offer the opportunity to gain direct experience
working, to develop self-confidence and to promote personal and
school perseverance. In addition to these overall findings, it appears
that engaging in social action increases the chances of success,
which could value the adolescent and strengthen his self-esteem.
On another note, the high self-esteem in the familial subscale
of this study could be explained by the reasonably balanced family
situations of these adolescents. In fact, most of them belonged to
high-income families (76.6%), lived with well-educated parents
(66.2% of fathers and 68.8% of mothers) and had a harmonious
relationship within their families (69%). These factors could foster
adolescents’ self-esteem especially that the family environment is a
major pillar on which self-esteem is built. It is worth mentioning
that parents in Tunisia are generally over involved in adolescents
‘lives and adolescents ‘peer relationships. They supply their children
with enough security, affection and attention, which are very
important in the development of a child’s abilities and perception.
In the school subscale, more than one third of respondents (35.6%)
had high self-esteem. This would seem a reasonable result given the
fact that 78.9% of them had an academic average equal to or greater
than 13/20 in the 2017-2018 school year.
Moreover, previous research has shown the significant
relationship between prosocial behavior, high self-esteem12,
academic success13,14 and good relations with peers15, which is
consistent with the findings of the present study.
According to our study, there was no significant relationship
between self-esteem and the sex of the adolescent. However, various
studies undertaken on western samples had already provided
evidence for self-esteem gender variation16-18. In these studies,
self-esteem measurement considered the physical dimension, as
physical self-esteem is particularly relevant during adolescence and
differs considerably depending on the gender. In fact, physical self-
esteem is the evaluation of oneself as a physical person, including
attractiveness, health, and physical limitations and prowess19. In
this way, the huge gender differences in many Western societies
could be explained by the cultural emphasis on girls and women’s
physical appearance. Numerous studies have shown that girls’
attitudes toward their appearance become more negative during
adolescence20. This decline in girls’ perceived physical attractiveness
is supposed to have particularly negative effects on self-esteem
when cultural pressures regarding women’s physical appearance are
high. Yet, both males and females who feel physically attractive tend
to have higher self-esteem21,22.
We have to point out that, along with the gender variation,
interaction effects were found between ages on self-esteem23. In the
12 to 14 age group, girls have higher self-esteem than boys, while
in the 17 to 19 age group, boys have higher self-esteem than girls24.
Participants enjoying a high level of socio-economic
development had significantly better self-esteem (p<0.001). In fact,
social influences affecting youth are unavoidable, and self-esteem
is widely subjected to these influences. It is possible to imagine
that in our modern society, where social success is reflected in
financial capacities as well as in self-perception by others, the socio-
economic status can influence self-esteem.
Besides these structural factors, self-esteem also depends on
relational factors in both familial and peer groups. In this respect,
the present study showed that a high-conflict relationship with
parents, adolescents’ lack of involvement in decision making and
lack of communication with parents were associated to low total
self-esteem (respectively p=0.02; 0.009; 0.009). Research suggests
that the quality of the parental relationship influences healthy
development among children, including the development of their
self-esteem25. According to many youth-development specialists,
self-esteem may be derived to a significant extent from feelings
of self-worth and personal satisfaction that stem from their
experiences at school and mainly within their families26. In this
way, and as suggested by numerous empirical studies, family open
communication is positively related to self-esteem27. Moreover,
the quality of the adolescent–parent relationship helps adolescents
make decisions about their career choices by providing a secure
base and by facilitating the risk-taking behavior associated with
the decisional process. The adolescents’ ability to make decisions
strengthens their self-esteem, which in turn consolidates their
ego-identity development28. In this regard, paternal involvement
possibly increases the fulfillment and satisfaction among both
parents, which may be beneficial for the parent-child relationship
of both mother and father29. In fact, fathers play an active role in the
child’s identity construction, fostering the autonomy, independence
and self-confidence they need for a balanced affective life. This
might explain the significant relationship which has been found
between the participants’ total self-esteem and their fathers’
educational level (p=0.001). Of equal importance was the mothers’
educational level, the higher it was, the higher the adolescents’
self-esteem was (p<0.001). Well-educated parents provide more
support, more communication and more parent-child negotiation,
therefore, enhancing the child’s self-esteem.
Unlike the data in the literature, there was no significant
relationship between self-esteem of the participants and the
parenting style, as it was perceived by the participants (p=0.11).
This may be attributed to the absence of an objective assessment
based on a standardized psychometric scale. A Spanish study
involving 1445 adolescents showed that on the different self-
esteem criteria, children from indulgent homes obtained equal
or higher scores on family and physical self-esteem than those
from authoritative families; the lowest scores were detected in
children from authoritarian and neglectful families23. The greatest
family protection corresponded to parents with permissive and
democratic socialization styles. The children of these styles were
less vulnerable, obtaining higher scores on self-esteem.
According to our study, total self-esteem was higher in
adolescents with good friendship networks; however, the
relationship was not significant (p=0.1). This lack of correlation
may be due to the multi-dimensionality of total self-esteem,
comprising general and school subscales in addition to the social
subscale. Different psychological theories postulate adolescents’
self-esteem is particularly shaped by social feedback and the sense
of being liked by others. In fact, during adolescence, not only peers
relationships increase in importance, but also peers expectations,
opinions, and actions become more important for adolescents self-
images30.
Besides, self-satisfaction was linked to school success, in our
study. Participants with high self-esteem had significantly higher
academic averages (p=0.001). In the same way, some studies
evidenced that students with better educational performances
showed higher levels of self-esteem31. Others found that self-
esteem may relate to higher aspirations which may then connect
to academic performance. Indeed, the relationship between self-
 Nada C / Arch Clin Psychiatry. 2021;48(1): 51-56
esteem and academic achievement may be positive but may also
be affected by other factors such as one’s perseverance and passion
towards goals32.
Finally, our results showed that practice of extracurricular
activities was associated to high self-esteem (p=0.01). In half of the
cases (50%), those activities consisted of sports. Individuals’ sports
participation is associated with their self-esteem33. For example,
perceived physical competence and physical self-worth contribute
to higher self-esteem in sport participants. Time spent in sporting
activities gives opportunities to build sport competencies and, in
turn, the self-concept of abilities. In addition, contrary to low sport
self-concept, high sport self-concept in children leads to high self-
esteem34.
Conclusion
The present study evidenced relatively high rates of high self-
esteem among adolescents with prosocial behavior in the city of
Sfax (Tunisia). It also highlighted the role of structural factors such
as family’s income and interpersonal relationships in determining
self-esteem in adolescence. This allows to affirm that the outlined
difference in the self-esteem clearly pertains less to the prosocial
behavior and to its specificities than to the adolescence commonly
observed processes. Furthermore, our results emphasized the
crucial role of academic success as a predictable indicator of high
self-esteem. It has potential implications for educational programs
targeted at adolescents' positive development. Consequently,
reforms of the educational system should take into account the
self-esteem dimension, not only by encouraging socialization and
communication but also by fostering sports education. Parents
and teachers should also encourage adolescents to engage in more
frequent and higher quality prosocial behavior as one potential
avenue of fostering self-esteem.
Despite the many contributions made by the current study, there
are limitations that could be improved in future research. First, our
study population consisted of 90 adolescents who were recruited
in one city in Tunisia (Sfax); it was therefore not representative
of the Tunisian adolescents. It would be interesting to broaden
the sample to include Tunisian adolescents from other cities so
that our findings could be more relevant. The second limitation is
related to the reliance on correlational data. Thus, it is necessary
to conduct further longitudinal research to examin the effects of
prosocial behavior toward different targets on self-esteem during
adolescence.
The study was conducted in the Psychiatry C department,
Hedi Chaker university hospital, Sfax, TUNISIA
Acknowledgement: No Acknowledgement
References
1. Nilsen W, Karevold E, Røysamb E, Gustavson K, Mathiesen KS. Social
skills and depressive symptoms across adolescence: Social support as a
mediator in girls versus boys. J Adolesc. 2013;36(1):11–20.
2. Heijden H van der. Improving self-esteem and well-being in adolescence
through improving peer acceptance [Master’s Thesis]. 2018.
3. Layous K, Nelson SK, Oberle E, Schonert-Reichl KA, Lyubomirsky
S. Kindness counts: Prompting prosocial behavior in preadolescents
boosts peer acceptance and well-being. PloS One. 2012;7(12):e51380.
4. Tay S, Eisenberg N. Empathy, prosocial behavior, and positive
development in schools. In: Handbook of positive psychology in schools.
Routledge; 2014. p. 90–106.
5. Zuffianò A, Alessandri G, Kanacri BPL, Pastorelli C, Milioni M,
Ceravolo R, et al. The relation between prosociality and self-esteem
from middle-adolescence to young adulthood. Personal Individ Differ.
2014;63:24–29.
55
6. Kanacri BPL, Pastorelli C, Zuffianò A, Eisenberg N, Ceravolo R, Caprara
GV. Trajectories of prosocial behaviors conducive to civic outcomes
during the transition to adulthood: The predictive role of family
dynamics. J Adolesc. 2014;37(8):1529–1539.
7. Valkenburg PM, Koutamanis M, Vossen HG. The concurrent and
longitudinal relationships between adolescents’ use of social network
sites and their social self-esteem. Comput Hum Behav. 2017;76:35–41.
8. Harter S. Comment se forge l’image de soi chez l’adolescent. M Bolognini
B. 1994;
9. Fu X, Padilla-Walker LM, Brown MN. Longitudinal relations between
adolescents’ self-esteem and prosocial behavior toward strangers,
friends and family. J Adolesc. 2017;57:90–98.
10. Coopersmith S. Inventaire d’estime de soi de S. Coopersmith: SEI.
Editions du Centre de psychologie appliquée; 1984.
11. Chiu L-H. Measures of self-esteem for school-age children. J Couns Dev
JCD. 1988;66(6):298.
12. Caprara GV, Barbaranelli C, Pastorelli C, Bandura A, Zimbardo PG.
Prosocial foundations of children’s academic achievement. Psychol Sci.
2000;11(4):302–306.
13. Guo Q, Zhou J, Feng L. Pro-social behavior is predictive of academic
success via peer acceptance: A study of Chinese primary school children.
Learn Individ Differ. 2018;65:187–194.
14. Gerbino M, Zuffianò A, Eisenberg N, Castellani V, Luengo Kanacri BP,
Pastorelli C, et al. Adolescents’ prosocial behavior predicts good grades
beyond intelligence and personality traits. J Pers. 2018;86(2):247–260.
15. Hofmann V, Müller CM. Avoiding antisocial behavior among
adolescents: The positive influence of classmates’ prosocial behavior. J
Adolesc. 2018;68:136–145.
16. Bégarie J, Maïano C, Ninot G. Concept de soi physique et adolescents
présentant une déficience intellectuelle: Effets de l’âge, du sexe et de la
catégorie de poids. Can J Psychiatry. 2011;56(3):179–186.
17. Bouffard T, Seidah A. Perceptions de soi a l’adolescence: differences
entre filles et garcons. Enfance. 2004;(4):405–420.
18. Fourchard F, Courtinat-Camps A. L’estime de soi globale et physique à
l’adolescence. Neuropsychiatr Enfance Adolesc. 2013;61(6):333–339.
19. Musetti A, Corsano P. Multidimensional self-esteem and secrecy from
friends during adolescence: The mediating role of loneliness. Curr
Psychol. 2019;1–9.
20. Phares V, Steinberg AR, Thompson JK. Gender differences in peer
and parental influences: Body image disturbance, self-worth, and
psychological functioning in preadolescent children. J Youth Adolesc.
2004;33(5):421–429.
21. Bleidorn W, Arslan RC, Denissen JJ, Rentfrow PJ, Gebauer JE, Potter J, et
al. Age and gender differences in self-esteem—A cross-cultural window.
J Pers Soc Psychol. 2016;111(3):396.
22. Kling KC, Hyde JS, Showers CJ, Buswell BN. Gender differences in self-
esteem: a meta-analysis. Psychol Bull. 1999;125(4):470.
23. Riquelme M, Garcia OF, Serra E. Psychosocial maladjustment in
adolescence: Parental socialization, self-esteem, and substance use. An
Psicol. 2018;34(3):536.
24. Anne Modrcin-Talbott M, Pullen L, Ehrenberger H, Zandstra K,
Muenchen B. Self-esteem in adolescents treated in an outpatient mental
health setting. Issues Compr Pediatr Nurs. 1998;21(3):159–171.
25. Orth U. The family environment in early childhood has a long-term
effect on self-esteem: A longitudinal study from birth to age 27 years. J
Pers Soc Psychol. 2018;114(4):637.
26. Krauss S, Orth U, Robins RW. Family environment and self-esteem
development: A longitudinal study from age 10 to 16. J Pers Soc Psychol.
2019;
27. Noller P, Callan V. The adolescent in the family. Routledge; 2015.
28. Emmanuelle V. Inter-relationships among attachment to mother and
father, self-esteem, and career indecision. J Vocat Behav. 2009;75(2):91–
99.
29. Lamb ME. How do fathers influence children’s development? Let me
count the ways. Role Father Child Dev. 2010;1–27.
30. Ragelienė T. Links of adolescents identity development and relationship
with peers: A systematic literature review. J Can Acad Child Adolesc
Psychiatry. 2016;25(2):97.
56 Nada C / Arch Clin Psychiatry. 2021;48(1): 51-56

31. Wagner J, Lüdtke O, Robitzsch A, Göllner R, Trautwein U. Self-esteem
development in the school context: The roles of intrapersonal and
interpersonal social predictors. J Pers. 2018;86(3):481–497.
32. Weisskirch RS. Grit, self-esteem, learning strategies and attitudes and
estimated and achieved course grades among college students. Curr
Psychol. 2018;37(1):21–27.
33. Qurban H, Wang J, Siddique H, Morris T, Qiao Z. The mediating role of
parental support: The relation between sports participation, self-esteem,
and motivation for sports among chinese students. Curr Psychol.
2019;38(2):308–319.
34. Gul Ö, Caglayan HS. The relation between the self-esteem levels and
decision-making styles of the students doing sports and the students not
doing sports in high schools. Turk J Sport Exerc. 2017;19(2):228–233.
 Review article

Pharmacologic Treatment of Antidepressant-Induced Excessive Sweating: A Systematic

Review
Summer R. Thompson1*
https://orcid.org/0000-0003-3263-1774
Laura E. Compton2
https://orcid.org/0000-0002-5826-0855
Min-Lin Fang3
https://orcid.org/0000-0002-8997-5677
Jyu-Lin Chen1
https://orcid.org/0000-0003-3263-1774

1University of California, San Francisco, USA

2California State University East Bay, California, USA
3University of California, San Francisco Academic Health Sciences Library, San Francisco, USA

Received: 09-07-2019 – Accepted: 20-11-2020

DOI: 10.1590/0101-60830000000279

ABSTRACT
Background: Antidepressant-induced excessive sweating (ADIES) is a side effect noted to occur in over 20% of patients taking antidepressant
medications (Marcy & Britton, 2005). Understanding the effect of pharmacological management of this side effect may allow patients to
continue with their current antidepressant medication regimen.
Aims: The aims of this systematic review are to identify medications to successfully manage ADIES, to describe the timeline between
initiation of treatment and resolution of ADIES and/or follow-up assessment, and to describe any subgroups that exist related to ADIES
treatment efficacy.
Methods: This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews
and Meta-Analyses) guidelines. We conducted a search of ten major electronic databases resulting in 3,922 studies that addressed the
pharmacologic management of ADIES.
Results: We identified seven studies that met the inclusion criteria. These studies varied greatly in study methodology and analysis methods
used. Although all studies reported positive results from the various interventions used, the degree of bias differed between studies.
Conclusions: The frequency of this side effect and the lack of research on this topic warrant further research into treatment options. The
pervasiveness of ADIES also entails enhanced patient education, assessment and management.

Thompson SR / Arch Clin Psychiatry. 2021;48(1):57-65

Keywords: antidepressant, hyperhidrosis, diaphoresis, sweating, side effects

INTRODUCTION Antidepressant-induced excessive sweating (ADIES)

Antidepressant prescribing and adherence
Antidepressants are one of the most commonly prescribed classes
of medication worldwide, and global use increased significantly
between 2000 and 2015, with a 45% increase in some countries1-3.
In 2015 alone, 150 million prescriptions were written for
antidepressants in the United States for the treatment of psychiatric
and medical disorders4. The goal of antidepressant therapy,
regardless of the condition being treated, is to achieve full remission
of symptoms with no or minimal side effects5. Medication
adherence is an important issue in accomplishing this goal and can
be one of the largest hurdles to overcome in achieving symptom
management6. Research has shown that up to 87.6% of individuals
who are taking antidepressant medications do not adhere to their
prescribed medication regimen7. Intolerable side effects, including
sexual dysfunction, weight gain, sleep disturbance and excessive
sweating, play a large role in non-adherence6,8.
Antidepressant-induced excessive sweating (ADIES) is a side
effect that has been documented in up to 22% of patients who take
antidepressant medications9,10. This side effect occurs commonly
in all antidepressant classes, including selective serotonin reuptake
inhibitors (SSRIs), selective serotonin and norepinephrine reuptake
inhibitors (SNRIs) and tricyclic antidepressants (TCAs)10,11. ADIES
can be a source of embarrassment for many patients, resulting
in impairment in both social and occupational functioning. The
loss of fluids caused by ADIES may also pose an increased risk
for dehydration or electrolyte deficiency in at-risk populations10.
ADIES can cause significant frustration for patients who have
achieved full or partial remission of their symptoms by taking
an antidepressant12. Patients who develop ADIES are faced with
the decision of either continuing an offending antidepressant
medication and living with a side effect that can be difficult to
tolerate, or stopping the medication, risking relapse of symptoms,
and having no certainty that a new antidepressant will manage their
symptoms to the same degree, if at all11.

Address for correspondence: Summer R. Thompson, University of California, San Francisco, 2 Koret Way, San Francisco, CA 94143, USA, Tel: +1 (707) 363-6446; Fax: +1 (707) 451-2324; E-mail:
summer.thompson@ucsf.edu
58 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65
Multiple pathoaetiologies of excessive sweating have been proposed,
but the exact underlying mechanisms remain poorly understood.
TCAs and SNRIs may result in ADIES by inhibiting norepinephrine
reuptake, causing excessive stimulation of peripheral adrenergic
receptors, which then produces excessive sweating10,13-16. SSRIs and
SNRIs have been hypothesised to exert excessive serotonergic effects
on the hypothalamus, resulting in disruption of thermoregulation
and subsequently causing an inappropriate sweating response9,11,17,18.
Regardless of the mechanism, ADIES presents a significant risk
for low medication adherence and decreases the quality of life for
individuals who take antidepressants.
Pharmacological interventions in ADIES
A variety of pharmacological and nonpharmacological approaches
are available to address medication-induced excessive sweating.
Pharmacological interventions include decreasing the dose of the
offending antidepressant, complete change of medication or the
addition of a medication that directly targets this side effect.10,11
Non-pharmacological strategies include behavioural modifications
such as reducing anxiety, reducing caffeine and alcohol use,
wearing absorbent clothing, and modifying exposure to warm
environments10. Pharmacological treatment of excessive sweating
can be an approach that mitigates this side effect while preventing
the discontinuation of an otherwise helpful antidepressant agent.
Study aims
The existing literature related to the treatment of ADIES is sparse
compared with that for other antidepressant side effects, and it
relies heavily on case reports. To the authors’ knowledge, this is
the first systematic review to address the topic of pharmacological
treatment of ADIES. Thus, the aims of this systematic review were
to (a) describe the efficacy of medication used to treat ADIES,
(b) describe the timeline between initiation of treatment and
resolution of ADIES and/or follow-up assessment, and (c) describe
any subgroups that exist related to ADIES treatment efficacy. By
understanding the efficacy of medications used to treat ADIES
from a systematic review of the literature, health care providers
can determine the appropriate pharmacological treatment and
treatment trajectory for managing it.
METHODS
This systematic review was conducted and reported in accordance
with the PRISMA (Preferred Reporting Items for Systematic
Reviews and Meta-Analyses) guidelines19
Data sources
The authors conducted a search of ten databases (PubMed,
Embase, Web of Science, BIOSIS, CINAHL, JBI Database,
PsycINFO, ClinicalTrials.gov, ICTRP Search Portal, and Cochrane
CENTRAL), the “times cited” link in Web of Science for included
studies, and a reference list of all included studies. This systematic
review was registered in PROSPERO, the international prospective
register for systematic reviews, to ensure that such a systematic
review had not been previously conducted (Registration Number
CRD42019089193). The search was performed by using a
combination of keywords and truncation when appropriate to
capture all relevant variations in terminology. Search terms were
categorised into three groups: (a) terms associated with sweat
(group 1); (b) terms associated with specific antidepressants
(generic and most common brand name), as well as the general term
antidepressant (group 2); and (c) the exact phrase “antidepressant
induced excessive sweating” (group 3, Table 1). Minor variations
in the searches were necessary because of the constraints imposed
by interface parameters of the individual databases. The authors
can be contacted for specific search strategies pertaining to each
individual database. The search was conducted in October 2018.
Inclusion/exclusion criteria
Inclusion and exclusion criteria were determined prior to the
screening process to reduce potential bias. Inclusion criteria
consisted of studies that (a) referenced ADIES and (b) addressed
the pharmacological treatment of sweating related to antidepressant
medications. No limitations were placed regarding country or
language of origin. No time frame limitations were specified
because of the scarce number of studies related to this topic. The
earliest study that met inclusion criteria was published in 2002 and
the most recent studies were published in 2013.
Exclusion criteria consisted of studies that (a) did not include
pharmacological treatment for ADIES, (b) treated sweating
caused by essential hyperhidrosis and hyperhidrosis related to
a medical condition (i.e. menopause, cancer, etc.), (c) included
antidepressants that have been removed from the market, (d)
included pharmacological treatment for ADIES that have been
removed from the market, and (e) comprised single case reports,
unpublished manuscripts (i.e. dissertations), editorials and opinion
papers because of the innate low quality of evidence.
Methodological rigor assessment
Methodological rigor was assessed by using tools adapted from the
National Heart, Lung, and Blood Institute Study Quality Assessment
Tools (which included the Quality Assessment of Controlled
Intervention Studies, the Quality Assessment for Before-After (Pre-
Post) Studies With No Control Group, and the Quality Assessment
for Case Series Studies tools)20.
Each item for all three tools was scored as 0 (not met), 1 (met),
not applicable (equivalent to 0), or cannot determine (equivalent to
0). From the total points, each of the studies evaluated was placed
into the category of good, fair or poor quality. The case series tool
consisted of nine items with a maximum possible score of 9 points.
The quality of case series was determined by the final score after
evaluation, with score ranges appraised as good (8-9), fair (6-7) or
poor (0-5). The pre-post-test study tool consisted of 12 items with
a maximum possible score of 12 points. Pre-post-test quality score
ranges were appraised as good (10-12), fair (8-9) or poor (0-7). The
randomised control trial (RCT) tool consisted of 14 items with a
maximum possible score of 14 points. Final scores for RCTs were
appraised as good (12-14), fair (8-11) or poor (0-7). Two reviewers
(S.R.T. and L.C.) extracted data from the articles included in this
review and independently assessed the quality of included studies
depending on the type of study being evaluated. A third reviewer
(J.-L.C.), who specialises in systematic review methodology, acted
as the tie breaker when consensus could not be reached.
RESULTS
Screening
The original search resulted in 3922 abstracts that were uploaded
into Endnote 9.0 for further evaluation. After duplicates were
eliminated, a total of 2368 publications were considered for review.
Titles and abstracts of the selected publications were then screened
for the presence of a pharmacological intervention for treating
ADIES, which yielded 44 articles. These 44 full-text articles were
screened and those that addressed primary hyperhidrosis, that
were single case studies or were letters to the editor were excluded,
yielding seven articles that met inclusion criteria (Figure 1). The
bibliographies of included studies were hand searched, and
promising titles were reviewed to locate articles not catalogued in
the major databases. No additional studies were identified in the
hand search.
 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65 59

Table 1. Search terminology

Group terms 1 and 2 combined by ‘AND’ and group term 3 combined by ‘OR’
Combined by “OR”
→group term 1
Group 1 | Group 2
Sweating Antidepressant
Sweat Antidepressant drugs
Hyperhidrosis Antidepressant*
Diaphoresis Thymoanaleptics
Thymoleptics
Antidepressive agent
Antidepressive agents
Amitriptyline OR Elavil
Amitriptylinoxide OR Amioxid
Amoxapine OR Asendin
Atomoxetine OR Strattera
Bifemelane OR Alnert
Bupropion OR Wellbutrin
Citalopram OR Celexa
Clomipramine OR Anafranil
Desipramine OR Norpramin
Desvenlafaxine OR Pristiq
Dibenzepin OR Noveril
Dimetacrine OR Istonil
Dosulepin OR Prothiaden
Combined by “OR”
→group term 2
Doxepin OR Sinequan
Duloxetine OR Cymbalta
Escitalopram OR Lexapro
Fluoxetine OR Prozac
Fluvoxamine OR Luvox
Imipramine OR Tofranil
Isocarboxazid OR Marplan
Levomilnacipran OR Fetzima
Lofepramine OR Gamanil
Maprotiline OR Ludiomil
Melitracen OR Adaptol
Metralindole OR Inkazan Tranylcypromine OR Parnate
Mianserin OR Tolvon
Milnacipran OR Savella
Mirtazapine OR Remeron
Moclobemide or Depnil
Nitroxazepine OR Sintamil
Nortriptyline OR Pamelor
Noxiptiline OR Nogedal
Opipramol OR Insidon
Combined by “OR”
→group term 3
| Group 3
Paroxetine OR Paxil “Antidepressant
Phenelzine OR Nardil induced excessive
Pipofezine OR Azaphen sweating”
Pirlindole OR Lifril
Protriptyline OR Vivactil
Reboxetine OR Edronax
Sertraline OR Zoloft
Setiptiline OR Tecipul
Selegiline OR Emsam
Toloxatone OR Humoryl
Teniloxazine OR Lucelan
Trimipramine OR Surmontil
Trazodone OR Desyrel
Venlafaxine OR Effexor
Vilazodone OR Viibryd
Vortioxetine OR Trintellix
Viloxazine OR Vivalan

Characteristics of studies included and key findings
Four of the included studies were case series , two were 21-24
double-blinded RCTs12,25, and one study was a non-random
quasi-experimental design of a combination of two open-label,
uncontrolled clinical trials.26 The included studies are summarised
in Table 2.
Antidepressant medications were used to treat a variety of
psychiatric diagnoses in the included studies: agoraphobia (n=1)21,
bipolar II disorder (n=1)22, depression not otherwise specified (n
= 1)23, dysthymia (n = 3)24, major depressive disorder (n = 205,
including two specified “with psychotic features”)26, panic disorder
(n = 2)25, and obsessive-compulsive disorder (n = 2)12.
Antidepressant medications implicated as the cause of ADIES
included SNRIs (duloxetine [n = 4], 60 mg daily; venlafaxine [n =
9] from 150 mg to 375 mg daily), SSRIs (citalopram [n = 3], 60 mg
daily; escitalopram [n = 3] [dosage not reported], fluoxetine [n =
5] from 20 mg to 80 mg daily; paroxetine [n = 2] from 30 to 40
mg daily; sertraline [n = 279] from 25 mg to 100 mg daily), TCAs
(clomipramine [n = 3] from 75 to 100 mg daily; nortriptyline [n =
1], 150 mg daily), and aminoketone antidepressants (bupropion [n
= 5], 300 mg daily). Dosages were not reported for all patients12,21-26.
The four case series studies relied on patient reports of sweating
severity and side effects as their only outcome measurements and
did not report the use of standardised measurement tools21-24.
The Hyperhidrosis Disease Severity Scale (HDSS) was the most
frequently used measurement tool12,25,26. Mago et al.26 used a variety
of measurement tools, including the Clinical Global Impression
Scale, the Illness Intrusiveness Rating Scale (used in study 2 only),
the Quality of Life Enjoyment and Satisfaction Questionnaire-Short
Form, and the Systematic Assessment for Treatment-Emergent
Events-General Inquiry (study 2 only). Ghaleia et al.25 also used
a self-report side effects questionnaire at the end of the treatment
period.
Data extraction and synthesis
Of the four case series studies reviewed, one was rated as moderate
quality and three were rated as poor quality21-24. The pre-post-test
quasi experimental study was rated as poor quality26. One RCT was
rated as moderate quality and the other as good quality (Tables
3-5)12,25.
The following data from these seven studies were extracted
and synthesised: author; publication year; sample characteristics;
offending antidepressant name, class, and dosage; study design;
duration; intervention name, dosage, and timing; comparators;
blinding methods; outcome measurement tools; analyses; and
outcomes, including side effects from the intervention (see Table 2).
The risk of bias was determined with the National Heart,
Lung, and Blood Institute Study Quality Assessment Tools. All of
the case series studies suffered from selection bias21-24. Both of the
RCTs reported measures to limit selection bias, including random
sequence generation12 and allocation concealment, but could not
exclude selection bias, because only participants who were willing
and able to follow the study protocol were included25. Both of
the RCTs reported measures to limit performance bias (blinding
of participants and personnel) and detection bias (blinding of
outcome assessors). Ghaleia and colleagues25 avoided attrition bias
 60 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65

PubMed 444
Embase 2005
Web of Science 365
BIOSIS 270
CINAHL 107
JBI Database 12
PsycINFO 77 Additional records identified
Identification

ClinicalTrials.gov 3 through searchof reference

ICTRP Search Portal 3 lists from selected articles by
Cochrane CENTRAL 374 using Web of Science and
Records identified through from other sources
database searching (n = 262)
(n = 3660)
Screening

Records after duplicates removed

(n = 2368) Records excluded with
reasons: did not meet
inclusion/exclusion
criteria, addressed
Records screened essential hyperhidrosis or
(n = 2368) hyperhidrosis related to a
medical conditionor
treatment of ADIES
(n = 2324)
Eligibility

Full-text articles assessed Full-text articles excluded

for eligibility meeting with reasons:
inclusion/exclusion criteria did not meet
(n = 44) inclusion/exclusion
criteria, single case
reports, unpublished
manuscripts, editorials
Included

and opinion papers

Studies included in (n = 37)
systematic review
(n = 7)

Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow chart. ADIES, antidepressant-induced excessive sweating.
 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65 61

Table 2. Characteristics of included studies

Author(s), date, Study type, inclusion Demographics Offending ADIES treatment Assessment tool, ADIES outcome/
location criteria, exclusion antidepressant, medication, statistical analysis, timing of ADIES
criteria dosage, class dosage, timing blinding remission or
follow-up

n=5 Fluoxetine 40 mg No time frame

Cyproheptadine 4
BID (SSRI) stated/ADIES
mg BID
eliminated and
51 y/o male maintained for 1
Caucasian, MDD, year
dysthymia, OCD No objective measure
Citalopram 60 mg stated: report of patient Sweating eliminated
Cyproheptadine 4
65 y/o female daily (SSRI) and maintained for
mg QHS
Caucasian, No statistical analysis 1 year
dysthymia, OCD stated
Ashton and Case series
Weinstein21 No blinding measures
Inclusion/ 58 y/o male Paroxetine 30 mg stated Sweating eliminated
Cyproheptadine 4
Location not stated exclusion criteria not Caucasian, panic QHS for 9 months
mg BID
stated disorder, MDD, (SSRI)
agoraphobia

56 y/o male
Caucasian, MDD Venlafaxine 375 mg Sweating eliminated
Cyproheptadine 4
daily (SNRI) and ADIEs
mg QHS
controlled for 9
32 y/o female months
Caucasian,
dysthymia Fluoxetine 40 mg Sweating reduced
Cyproheptadine 4
daily (SSRI), “markedly” and
mg QHS
venlafaxine 300 mg controlled for over 7
daily (SNRI) months

No objective measure Hyperhidrosis

n=2
stated: report of patient resolved in
Grootens 24 Clomipramine 100
Oxybutynin both instances
59 y/o male mg daily (tricyclic)
2.5 mg BID No statistical analysis completely. No
Location not stated Case series
stated time frame for
Clomipramine
re-evaluation of
Case series 75 mg daily
Oxybutynin No blinding measures intervention noted in
60 y/o male (tricyclic),
5 mg TID stated either case
lithium
Patient 1:
Fluoxetine 40 mg No objective measure
n=2 completely resolved
daily Aripiprazole stated: report of patient
sweating at 6-month
Lu et al.23 (SSRI) 10 mg daily
57 y/o female follow-up visit
No statistical analysis
Case series
Location not stated Duloxetine 60 mg stated
Patient 2: significant
daily Aripiprazole 20 mg
59 y/o female decrease in
(SNRI) daily No blinding measures
sweating at 2-week
stated
follow-up

n=3 Patient 1: “within

Venlafaxine 150 mg
a few days, the
daily
57 y/o female sweating was
(SNRI), Wellbutrin No objective measure
Terazosin 2 mg QHS 99.99% less”
300 mg daily stated: report of patient
(NDRI)
Patient 2: sweating
Mago and Monti22 No statistical analysis
resolved by 75%
Sertraline 75 mg stated
after 4 weeks,
Location not stated Case series daily
almost complete
(SSRI) No blinding measures
67 y/o male Terazosin 2 mg QHS resolution after 8
stated
weeks

Patient 3:
Paroxetine 40 mg
60-70% improved
daily
Clonidine 0.1 mg BID after 3 weeks,
(SSRI), nortriptyline
36 y/o male follow-up after 2
150 mg daily
years indicated
(tricyclic)
ongoing benefit
 62 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65

RCT HDSS used to assess

Follow-up
subjective sweating
assessment
Inclusion criteria:
occurred after 2
Ghaleila et al.25 MDD, treated with n = 140 Comparisons made
Sertraline: average weeks
sertraline for at between control and
dosage between 50
Behavioral least 14 days, ADIES Sample size intervention group
and 100 mg daily, Mean HDSS
Disorders and related to sertraline, determined to conducted by using
mean dosage 83 mg decreased
Substance Abuse physically healthy achieve statistical single t-tests and chi-
daily Oxybutynin 5 mg significantly, P =
Research Center, power of 0.80 with squared t-tests with
daily 0.000; η2 = 0.668
Farschian Hospital, Exclusion criteria: type I error of 0.05 respect to demographic
SSRI
Hamadan, Iran HTN, DMII, endocrine data, sweating
Time by group
disorders, psychiatric Mean age 37.69 ± location, and offending
Had to be taking the statistically
morbidity, substance 10.44 years antidepressant dose
antidepressant for significant
abuse, intolerable
at least 14 days for greater
side effects from 86 females (61.4%) SPSS version 19.0 for
improvement in
oxybutynin or Windows
treatment group, P =
placebo, pregnancy,
0.000, η2 = 0.139
breastfeeding Double blinded
n = 134
HDSS used to assess
severity of sweating
Sample size
Sweating
determined to Sertraline
Fisher’s exact test and significantly
achieve statistical (SSRI)
Mann-Whitney U -test reduced after 14-
power of 0.80 with
RCT used for comparison of day follow-up
type I error of 0.05, Duration of
Ghaleiha variables
analysis performed treatment with
et al.12 Inclusion criteria: without normal Mann-Whitney
with SPSS 16 sertraline between 4 Terazosin 1 mg at
MDD, taking distribution, and U-test showed
and 6 weeks bedtime
Behavioral sertraline for 4-6 independent difference with P
Age:
Disorders and weeks with ADIES sample t-test used < 0.001
terazosin 41 ± 13.5 Dose range Initial assessment
Substance Abuse for comparison of
y/o, placebo 38 ± terazosin group 65 performed and
Research Center, Exclusion criteria: numerical
11 y/o ± 30 mg follow-up occurred
Farschian Hospital, medical disorders, variables with normal Change in sweating
at 14 days
Hamadan, Iran substance abuse, distribution between outcomes:
Sex: Placebo: 59 25
any other psychiatric terazosin
terazosin male 28
disorder and placebo groups Grade 4: reduced
(41%), No significant
from 6 to 2
placebo 29 (44%) difference between
Statistical analysis Grade 3: 4 to 0
groups
performed with SPSS Grade 2: 28 to 20
Severity of
16 Grade 1: 30 to 46
sweating (Grade 4):
terazosin 33 (48.5%),
Double blinded
placebo 31 (47%)
All but one patient
Two open-label, pre- responded to
Venlafaxine (SNRI) HDSS used for terazosin; all others
post-test
n=5 screening of sweating noted significant
uncontrolled clinical
Duloxetine (SNRI) severity improvement in QOL
trials
n=3 related to ADIES
Escitalopram (SSRI) CGI for excessive CGI: median of 5
Inclusion criteria: n=3 Terazosin started at with range of 4-6
age 18-75, diagnosis sweating was used
1 mg every night at at baseline. Last
Mago et al. 26 Sertraline (SSRI) to evaluate overall
of MDD, ADIES: n = 23 bedtime, 2 weeks visit median of 2,
moderate severity at n=3 improvement
after screening range of 1-4 CGI
Outpatient services least twice a week Referred by
Bupropion (NDRI) improvement, P <
of Thomas Jefferson for 4 weeks, dosage physician and
n=2
Assessed weekly
IIRS .0001
University, PA change or changing
by newspaper Citalopram (SSRI) and increased by 1 PGI: scale rate
meds not feasible or
advertisements n=2 mg daily each week QLES Questionnaire- indicated 13
helpful for ADIES
Fluoxetine (SSRI) to a maximum of 6 Short Form patients considered
n=2 mg daily responsive to
Exclusion Pre hoc statistics treatment
not stated Clomipramine Data were analysed
criteria: history of HDSS: decreased
(tricyclic) n = 1 Most common with Stata 11.0. No
hyperthyroidism, from median of 3 to
Sertraline (SSRI) dosage 4 mg daily corrections
orthostatic median of 1, P = .002
and bupropion were made for multiple IIRS showed
hypotension,
(NDRI) n = 1 comparisons
priapism, abnormal significant
TSH and ED Venlafaxine (SRNI)
improvement, P =
medications and bupropion
(NDRI) n = 1 No blinding measures 0.003
QLES not significant
at 0/483
 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65 63

Table 3. Methodological rigor of included case series

Reference Study Study Consecutive Comparable Intervention Outcome Adequate Statistical Results MR
question population cases subjects clearly stated measures length of methods well score
stated stated clearly follow-up well described
and case stated described
definition
Ashton and
1 1 CD 1 1 0 1 0 0 5/9
Weinstein21
Grootens24 1 0 CD 1 1 0 CD 0 0 3/9
Lu et al.23 1 1 CD 1 1 0 1 0 1 6/9
Mago and
1 1 CD 0 1 0 1 0 1 5/9
Monti22
1, met requirement; 0, did not meet requirement MR, methodological rigor; CD, cannot determine.

Table 4. Methodological rigor of included pre-post study with no control

Reference Study Eligibility Participants All eligible Adequate Intervention Outcome Outcomes Loss to Pre and ITS Group- and MR
question criteria representative participants sample clearly measures assessors follow- post hoc design individual- score
stated stated of population enrolled size stated clearly blinded up 20% statistical level
defined or less analysis statistical
analysis
Mago et
1 1 1 CD CD 1 1 0 1 1 NA NA 7/12
al.26
ITS, interrupted time series; 1, met requirement; 0, did not meet requirement; MR, methodological rigor; CD, cannot determine; NA, not applicable

Table 5. Methodological rigor of included RCTs

Reference Study Adequate Interv Participants Outcome Groups Dropout Dropout Adherence Other Outcome Adequate Subgroups ITT MR
described Random- ention and assessors similar rate rate to interv measures sample prespecified analysis score
as RCT isation concealed providers blinded at <20% between protocols entions valid and size
blinded baseline groups between avoided reliable shown
<15% groups
Ghaleiha
1 1 1 1 1 1 1 1 1 1 1 1 0 0 12/14
et al.25
Ghaleiha
1 1 1 1 1 1 CD CD 1 1 1 1 0 0 10/14
et al.12

RCT, randomised control trial; ITT, intention-to-treat; 1, met requirement; 0, did not meet requirement; MR, methodological rigor; CD, cannot determine.

by reporting exclusions (n = 5, 3.4%) and reasons for exclusion and
did not include them in any analyses. The five attrition cases were
excluded because of intolerable adverse effects of the treatment
and placebo, yet were not included in their secondary outcomes
assessment of side effects, where that data seem relevant25. Ghaleia
and collegues12 did not report any attritions or exclusions.
Synthesis of results
What is the effectiveness of pharmacological treatments used to
treat ADIES?
Five pharmacological agents were used to treat ADIES in the seven
studies that we reviewed.
Terazosin (alpha-1 adrenergic blocker). Terazosin was
evaluated in 93 patients in dosages of 1 to 6 mg daily: one RCT
(n = 68, fair quality)12; one pre-post open-label, uncontrolled
clinical trial (n = 23, poor quality)26; and one case series (n = 2,
low quality)22. In all three studies, terazosin greatly reduced the
severity of sweating, and the difference between terazosin and
placebo reached statistical significance (P < 0.001)12. However,
there are significant discrepancies in the data (number of patients
with Grade IV sweating pre-intervention versus number of patients
with Grade I sweating post-intervention) reported by Ghaleia et
al.12 that decreased the validity of their results.
Oxybutynin (urinary anti-spasmodic). Oxybutynin was
evaluated in 68 patients in dosages of 5 mg daily in one RCT (n =
66, good quality)25 and one case series study (n = 2, low quality)24.
Ghaleia et al.25 found that the reductions in sweating in the
treatment group was statistically significant (P = 0.005), although
both treatment and control groups had a notable decrease in
sweating at the end of the treatment period (P = 0.03). Grootens24
also reported that oxybutynin relieved sweating via patient reports.
Cyproheptadine (histamine H1 antagonist/anti-serotonergic
agent). Cyproheptadine was evaluated in six patients across two
case series studies in dosages from 4 to 8 mg daily (n = 5, low
quality21; n = 1, low quality22). Mago22 found that cyproheptadine
had “minimal benefit” on sweating after several weeks, whereas
Ashton and Weinstein21 reported a reduction in sweating across all
patients per patient report.
Aripiprazole (second-generation [atypical] antipsychotic).
One case series study (n = 2, low quality23) reported improvement
in sweating with aripiprazole 10 mg daily, used primarily to treat
symptoms of bipolar II disorder and major depressive disorder with
psychotic features.
Clonidine (alpha-2 adrenergic agonist). One case series
study (n = 1, low quality22) reported a 60% to 70% improvement in
sweating with clonidine at a dosage of 0.2 mg daily after three weeks
in a patient who had not improved with cyproheptadine.
64 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65
What is the time to resolution of symptoms or outcomes at
follow-up assessment?
The timeline between initiation of treatment, improvement or
resolution of ADIES, and/or follow-up assessment varied widely
between studies, ranging from unspecified to two weeks to multiple
years after initiation of treatment medication. The four case
series studies did not clearly report duration between initiation
of treatment for ADIES and resolution of symptoms, but nine of
the 11 patients were followed for at least six months and up to two
years.21-24 Of the case series, only Grootens24 did not report any
time of follow-up or duration of treatment. Mago and colleagues26
reported two open-label, uncontrolled clinical trials consisting of a
two-week baseline period followed by a treatment period of up to
six weeks. Both RCTs12,25 consisted of a two-week treatment period.
See Table 2 for details related to timelines for either resolution of
symptoms or follow-up assessment of the individual studies.
What subgroups exist related to ADIES treatment efficacy?
In this systematic review, differences in treatment efficacy varied by
gender, as reported by one study.
Ghaleia and colleagues25 found a notable difference in sweating
severity by gender, with females experiencing significantly lower
mean HDSS scores compared with those of males in both the
treatment (oxybutynin) and placebo groups before and after
treatment.
DISCUSSION
Summary of evidence/results
Given the prevalence of ADIES and the large number of
antidepressant medications prescribed globally each year, there is
a surprising lack of data regarding effective treatment strategies.
Our systematic review of the literature provides the first critical
analysis of the current evidence on the effectiveness of various
pharmacological treatments for ADIES in patients who use
antidepressant medications. Although the results of this systematic
review identified several medications for treating ADIES, the length
of effect is undetermined. One study also found that female patients
are more likely to respond to medication treatment than are male
patients.
Key findings of the effectiveness of the reviewed pharmacological
interventions are that a variety of different medications have
the potential to reduce or eliminate the severity of ADIES. This
effectiveness is likely through a variety of mechanisms of action. It
can be hypothesised that terazosin, oxybutynin and clonidine act
on peripheral adrenergic receptors to reduce excessive stimulation
caused by antidepressants, thereby reducing or eliminating
excessive sweating10,27,28. Cyproheptadine and aripiprazole can
be hypothesized to reduce excessive serotonergic hypothalamic
stimulation, which then reduces excessive sweating10. Clinicians
who are aware of these potential pathoaetiologies of ADIES and the
mechanisms of action of these medications can make an educated
decision about ADIES management. If a patient has no reduction
in sweating with a medication that addresses excessive adrenergic
stimulation, then a trial of a medication that addresses excessive
serotonergic stimulation would be an appropriate next step. Future
research to clarify which medications most effectively address
ADIES in the context of antidepressant use would aid clinicians in
making a more informed decision regarding ADIES treatment.
A generalized statement regarding the time to resolution of
ADIES is difficult because of the variety of offending antidepressants,
interventions used and inconsistent documentation of the follow-
up evaluation. Within the literature reviewed, the shortest period
between initiation of treatment medication and follow-up was
two weeks. This suggests that providers may need to wait at least
two weeks for any notable decrease in ADIES symptoms. These
beneficial effects were also reported to last for years in some patients.
Clinicians can use this information to educate patients regarding
the expected time frame for ADIES improvement and duration of
medication effect. Further research that more accurately assesses
the time to reduction or elimination of ADIES would provide a
more accurate understanding of these time frames.
Few key findings could be arrived at in the analysis of subgroups
in the management of ADIES. The only study that addressed any
subgroups was conducted by Ghaleia and colleagues25, who noted
gender differences in the severity of sweating through the evaluation
of HDSS scores during both pre- and post-intervention of males
and females. Although they did not postulate a hypothesis as to
why these differences existed, it may be related to differences in
sensitivity to serotonin-modulating medications between genders.
Further research to understand the underlying mechanism of
action of ADIES is necessary to understand this difference between
genders. This would allow clinicians to make informed decisions
regarding the potential of medications to evoke ADIES in males
versus females.
Although the mechanism of action that results in ADIES is
relatively poorly understood, it is clear from the studies reviewed
that there are a number of different approaches to managing this
side effect. Stakeholders include the patient and the provider who
prescribes antidepressants, including, but not limited to, primary
care, psychiatry, pain management, neurology and other specialty
providers. This variety of possible approaches allows a provider
to tailor the management of ADIES to the individual patient,
depending on the patient’s overall clinical picture and preference.
The first step in managing ADIES is to recognise and assess the
symptoms, either through self-report of the patient or the use of the
validated four-point HDSS29.
The potential for generalisability of these findings is limited
because of the preponderance of low-quality evidence, small sample
sizes, and heterogeneity of offending antidepressant medications
and interventions used. Implications drawn from this review are
that both patients and prescribers need to be aware that excessive
sweating is a common potential side effect of antidepressants and
that it can be successfully managed with minimal disruption to the
patient’s antidepressant medication regimen.
Limitations
A number of limitations were encountered in conducting this
systematic review, most notably the paucity of high-quality
research in the form of blinded RCTs related to this subject. The
reliance on case series studies provides weak evidence to support
the recommendation of one pharmacological intervention over
another. The heterogeneity of study methods used, the variety of
offending antidepressant and treating medications, and the lack of
high-quality research limited the possibility of conducting a meta-
analysis. Notably, none of the studies reviewed addressed patients
with excessive sweating caused by antidepressants being used for
medical conditions. The risk of bias by the authors of this review
is limited because of the rigid nature of inclusion and exclusion
criteria, as well as the close collaboration with both a university
research librarian and an expert in systematic review methodology.
Recommendations for future research
The literature presented shows that research regarding the
management of ADIES is sparse; currently there exist only two
published RCTs that focused on two different pharmacological
 Thompson SR / Arch Clin Psychiatry. 2021;48(1): 57-65
interventions for treating ADIES, with only one specific
offending antidepressant12,25. Considering the sheer volume of
antidepressants prescribed annually for both psychiatric and non-
psychiatric diagnoses, as well as the relative frequency of this side
effect, further research on ADIES management is warranted11.
Additional well-designed RCTs are needed to evaluate the efficacy
of all medication interventions noted within this systematic
review, as well as other interventions that are efficacious for
hyperhidrosis and not discussed herein. Having a variety of well-
studied interventions would provide clinicians with the ability to
select from robust, evidence-based, patient-centric choices, as
well as allowing for multiple options should one intervention be
ineffective or intolerable. This research would also expand on our
limited knowledge regarding the mechanism of action for ADIES
and how to best treat it in the context of different antidepressants
and different antidepressant classes.
Conclusion
Hyperhidrosis in any context negatively impacts quality of life
and, in relation to antidepressant medications, is particularly
debilitating because it compounds pre-existing anxiety, depression
and social isolation, which contributes to reduced medication
adherence and poor patient outcomes. Considering the increasing
rates of use of antidepressant prescriptions for both psychiatric and
non-psychiatric diagnosis and the frequency of this side effect, the
lack of research on this topic is surprising. This review should serve
to prompt future research on ADIES management and encourage
prescribers to educate their clients, assess at routine intervals and
be deliberate in the management of ADIES.
Funding
This research received no specific grant from any funding agency,
commercial or not-for profit sectors.
References
1. Huang C-Y, Yang S-Y, Mojtabai R, Lin S-K, He Y-L, Chong M-Y, et al.
Trends of polypharmacy and prescription patterns of antidepressants in
Asia. J Clin Psychopharmacol 2018;38(6):598-603.
2. OECD Health Statistics: Pharmaceutical market [Data set on Internet].
OECD Publishing; 2012 [2019 June 20]. Available from https://doi.
org/10.1787/data-00545-en
3. OECD Health at a glance 2017 [Internet]. OECD; 2017 [2019 June 20].
Available from http://dx.doi.org/10.1787/19991312
4. Pratt LA, Brody DJ, Gu Q. Antidepressant use among persons aged
12 and over: United States, 2011-2014 [Internet]. Hyattsville (MD):
National Center for Health Statistics; 2017 [2019 June 20]. 8 p. NCHS
data brief no. 283. Available from https://www.cdc.gov/nchs/data/
databriefs/db283.pdf
5. Stahl SM. Why settle for silver, when you can go for gold? Response
vs. recovery as the goal of antidepressant therapy. J Clin Psychiatry
1999;60(4):213-4.
6. Sansone RA, Sansone LA. Antidepressant adherence: are patients taking
their medications? Innov Clin Neurosci 2012;9(5-6):41-6.
65
7. Sheehan DV, Keene MS, Eaddy M, Krulewicz S, Kraus JE, Carpenter DJ.
Differences in medication adherence and healthcare resource utilization
patterns: older versus newer antidepressant agents in patients with
depression and/or anxiety disorders. CNS Drugs 2008;22(11):963-73.
8. Ferguson JM. SSRI antidepressant medications: adverse effects and
tolerability. Prim Care Companion J Clin Psychiatry 2001;3(1):22-7.
9. Marcy TR, Britton ML. Antidepressant-induced sweating. Ann
Pharmacother 2005;39(4):748-52.
10. Cheshire WP, Fealey RD. Drug-induced hyperhidrosis and hypohidrosis:
incidence, prevention and management. Drug Saf 2008;31(2):109-26.
11. Beyer C, Cappetta K, Johnson JA, Bloch MH. Meta-analysis: risk of
hyperhidrosis with second-generation antidepressants. Depress Anxiety
2017;34(12):1134-46.
12. Ghaleiha A, Shahidi KM, Afzali S, Matinnia N. Effect of terazosin on
sweating in patients with major depressive disorder receiving sertraline:
a randomized controlled trial. Int J Psychiatry Clin Pract, 2013;17(1):44-
7.
13. Butt MM. Managing antidepressant-induced sweating. J Clin Psychiatry
1989;50(4):146-7.
14. Garber A, Gregory RJ. Benztropine in the treatment of venlafaxine-
induced sweating. J Clin Psychiatry 1997;58(4):176-7.
15. Pierre JM, Guze BH. Benztropine for venlafaxine-induced night sweats.
J Clin Psychopharmacol 2000;20(2):269.
16. Mago R. Glycopyrrolate for antidepressant-associated excessive
sweating. J Clin Psychopharmacol 2013;33(2):279-80.
17. Buecking A, Vandeleur CL, Khazaal Y, Zullino DF. Mirtazapine in drug-
induced excessive sweating. Eur J Clin Pharmacol 2005;61(7):543-44.
18. Kolli V, Ramaswamy S. Improvement of antidepressant-induced
sweating with as-required benztropine. Innov Clin Neurosci 2013;10(11-
12):10-1.
19. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items
for systematic reviews and meta-analyses: the PRISMA statement. Ann
Intern Med 2009;151:264-9.
20. National Heart, Lung, and Blood Institute. Study quality assessment
tools [Internet]. Bethesda (MD): National Institutes of Health; [2019
June 20]. Available from https://www.nhlbi.nih.gov/health-topics/
study-quality-assessment-tools.
21. Ashton AK, Weinstein WL. Cyproheptadine for drug-induced sweating.
Am J Psychiatry 2002;159(5):874-5.
22. Mago R, Monti D. Antiadrenergic treatment of antidepressant-induced
excessive sweating in 3 patients. J Clin Psychiatry 2007;68(4):639-40.
23. Lu BY, Cullen CE, Eide CE, Williams CC, Apfeldorf WJ. Antidepressant-
induced sweating alleviated by aripiprazole. J Clin Psychopharmacol
2008;28(6):710-1.
24. Grootens KP. Oxybutynin for antidepressant-induced hyperhidrosis.
Am J Psychiatry 2011;168(3):330-1.
25. Ghaleiha A, Jahangard L, Sherafat Z, Ahmadpanah M, Brand S,
Holsboer-Trachsler E, et al. Oxybutynin reduces sweating in depressed
patients treated with sertraline: a double-blind, placebo-controlled,
clinical study. Neuropsychiatr Dis Treat 2012;8:407.
26. Mago R, Thase ME, Rovner BW. Antidepressant-induced excessive
sweating: clinical features and treatment with terazosin. Ann Clin
Psychiatry 2013;25(3):186-92.
27. Leeman CP. Pathophysiology of tricyclic-induced sweating. J Clin
Psychiatry 1990;51(6):258-9.
28. Demling J, Beyer S, Kornhuber J. To sweat or not to sweat? A hypothesis
on the effects of venlafaxine and SSRIs. Med Hypotheses 2010;74(1):155-
7.
29. Kowalski JW, Eadie N, Dagget S, Lai PY. Validity and reliability of the
Hyperhidrosis Disease Severity Scale (HDSS). J Am Acad Dermatol
2004;50(3):51.
 Brief Report

Prophylactic laxatives in clozapine-treated patients: a long road ahead

Raúl Alberto Estevez-Cordero1

Teresa Morera-Herreras1,2
0000-0002-7601-4914
Rafael Hernandez3

Juan Medrano4

Susanna Every-Palmer5
https://orcid.org/0000-0001-6455-9741
Unax Lertxundi6
https://orcid.org/0000-0002-9575-1602

1Department of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
2Neurodegenerative Diseases Group, BioCruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain
3Internal Medicine Service. Araba Psychiatric Hospital. Araba Mental Health Network, C/alava 43, 01006 Vitoria-Gasteiz. Alava. Spain

4Biocruces Bizkaia Health Research Institute, Mental Health Network Research Group, Osakidetza, Bizkaia, Spain

5Head of Department. Department of Psychological Medicine, University of Otago, Wellington, New Zealand

6Bioaraba Health Research Institute; Osakidetza Basque Health Service, Araba Mental Health Network, Araba Psychiatric Hospital, Pharmacy Service, Vitoria-Gasteiz, Spain

Received: 20-05-2020 – Accepted: 28-06-2020

DOI: 10.1590/0101-60830000000280

ABSTRACT
Introduction: In recent years, higher rates of mortality have been recorded from clozapine-induced gastrointestinal hypomotility than from
agranulocytosis. Still, this adverse reaction does not receive enough attention. Some authors recommend prophylactic laxatives for every
clozapine-treated patient but little information exists about laxative use in this patient cohort.
Methods: To conduct this study we identified all patients treated with clozapine of Araba, Northern Spain. To identify eligible patients
we used PRESBIDE which contains all outpatient prescription medications funded or not by the drug benefit plan. We measured the
medication possession ratio (MPR) as an indirect measure of adherence both for clozapine and other medications including laxatives.
Results: A total of 217 clozapine-treated outpatients were included. Mean age was almost 47 years, and about three-quarters were male. The
most frequent reason for clozapine use was schizophrenia, and mean duration of clozapine treatment was 4.5 years. Six of the 217 patients
(2.7 %) had a laxative prescription, with a mean MPR of 8.4% in this therapeutic class.
Conclusions: Laxatives were under-utilized and adherence was poor. We recommend healthcare professionals educate clozapine-treated
patients and their families as to the risks of gastrointestinal hypomotility, offer prophylactic laxatives and advise patients to take them as
prescribed.

Estevez-Cordero RA / Arch Clin Psychiatry. 2021;48(1):66-68

Keywords: Laxatives, constipation, clozapine, adherence, gastrointestinal hypomotility

Introduction a regime is the Porirua Protocol developed in New Zealand, which

In recent years, higher rates of mortality have been recorded
from clozapine-induced gastrointestinal hypomotility (CIGH)
than from agranulocytosis1. This has driven the Food and Drug
Administration to warn that untreated constipation caused by
clozapine result in serious bowel problems2. Still, this dangerous
adverse reaction, affecting up to 80% of patients treated with this
antipsychotic3, does not receive enough attention from healthcare
professionals.
Based on the frequency3,4, potential deadly consequences5,6 and
challenges in the diagnosis of clozapine-induced gastrointestinal
hypomotility (CIGH)3, some authors7,8 advocate for prophylactic
laxative use, because waiting for the patient to report constipation
symptoms will fail to detect most cases of CIGH (as most people
with CIGH do not complain of constipation)3. An example of such
recommends a stimulant like docusate and senna tablets for all
people starting clozapine and adding macrogol as necessary8.
However, there is little information about how often laxatives
are co-prescribed with clozapine, even for patients on clozapine
exposed to additional drugs that could worsen constipation, such
as anticholinergics9.
Adherence to prescribed drugs is a key issue in schizophrenia10.
A lot of research has been conducted on antipsychotic adherence
for obvious reasons, but information about other therapeutic drug
classes, such as laxatives, is scarce or non-existent11. Not taking
laxatives as prescribed could have harmful consequences.
So, in this study, we aimed to measure the rates of laxative
utilisation and for the first time, adherence to these drugs in
clozapine-treated outpatients.

Address for correspondence: Unax Lertxundi, Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba Mental Health Network, Araba Psychiatric Hospital,
Pharmacy Service, Vitoria-Gasteiz, Spain. c/Alava 43, 01006 Vitoria-Gasteiz, Alava, Spain. Telephone: +34 945 00 65 33 Fax: +34 945 00 65 87
67 Estevez-Cordero RA / Arch Clin Psychiatry. 2021;48(1): 66-68

Method The Clinical Research Ethics Committee of the Basque Country

To conduct this cross-sectional prevalence study we identified all
patients treated with clozapine data in the Araba Mental Health
Network, the public health service providing care for the 327,967
inhabitants of the province of Araba, Northern Spain. To identify
eligible patients we used PRESBIDE, an administrative healthcare
database which contains all outpatient prescription medications
funded or not by the drug benefit plan.
We extracted data on age, gender, total dose, diagnosis and time
since clozapine initiation, and any laxative prescription (A06)12.
In addition, global anticholinergic burden was measured using
three different scales: The Anticholinergic Risk Scale (ARS)13 the
Anticholinergic Cognitive Burden Scale (ACB)14 and Duran´s list15.
The medication possession ratio (MPR) was used as an indirect
measure of adherence both for clozapine and other medications
including laxatives. MPR expresses the proportion of days of drug
supply received by a given patient, divided by a certain period of
time11. In our case, we chose an 8-month study period, from August
2019 to March 2020. Patients admitted to a hospital were excluded.
Only long-term medications were included, that is, those which
could be dispensed to the outpatient in the pharmacy during the
whole study period. Suboptimal adherence was considered when
mean MPR for all drugs was < 80%, as taking medication as
prescribed 75–80% of the time has been generally considered an
acceptable level of adherence16.
approved this study and it was in accordance with the Declaration
of Helsinki.
Descriptive statistics were used to summarize the results of the
survey. The t-test and the X2 test were applied to compare continuous
and categorical variables, respectively between those who received
laxatives and those who did not. Analyses were performed using
SPSS software (SPSS Statistics for Windows, Version 22.0. Armonk,
NY: IBM Corp).
Results
A total of 217 clozapine-treated outpatients were identified. Mean
age was almost 47 years, and about three-quarters were male. The
most frequent reason for clozapine use was schizophrenia, and
mean duration of clozapine treatment was 4.5 years.
Six of the 217 patients (2.7 %) had a laxative prescription, with
a mean MPR of 8.4% in these therapeutic class drugs. For patients
showed a MPR of 0%.
No differences in clozapine dose, duration of treatment or
anticholinergic burden were observed between patients with or
without laxatives. The proportion of patients with suboptimal mean
adherence to all prescribed drugs was higher in patients on laxatives
(66.7% versus 17.5%). Macrogol was the most frequently used
laxative (3) drug followed by lactulose (2) and bisacodyl (1). No
differences in anticholinergic burden were found between groups.
The main results are summarized in Table 1

Table 1. Clinical and demographical characteristics of outpatients on long-term clozapine

ALL PATIENTS LAXATIVE USE Significance
YES n = 6 NO n = 211
Age (years, Mean ± SD) 46.9 ± 10.9 58.5 ± 7.9 46.5 ± 10.8 p = 0.008
Gender (% male) 73,7% 50% 74.4% p = 0.18
Clozapine daily dose (mg, Mean ± SD) 296.9 ± 150.5 300 ± 221.3 296.8 ± 148.7 p = 0.96
Duration of clozapine treatment (days,
1529.10 ± 2993.7 1605.6 ± 963.3 1526.9 ± 3032.5 p = 0.95
Mean ± SD)
Total number of drugs 3.3 ± 1.8 6.8 ± 3.5 3.2 ± 1.7 p =0.002
Anticholinergic burden ± SD
ARS 3.8 ± 1.0 3.5 ± 0.54 3.8 ± 0.9 p = 0.44
ACB 3.6 ± 1.2 3.3 ± 0.51 3.6 ± 1.2 p = 0.56
Duran 3.6 ± 0.96 3.5 ± 0.83 3.6 ± 0.9 p = 0.75
Suboptimal adherence (Proportion of
18.8% 66.7% 17.5% p = 0.002
patients with MPR <80%)†

Diagnosis (n)*
204
F20-29 (Schizophrenia, schizotypal and
delusional disorders)
F30-39 (Mood [affective] disorders
14
G20
Parkinson´s Disease
2
Macrogol = 3
Prescribed laxative Lactulose = 2 -
Bisacodyl = 1
*One patient can have more than one diagnosis
† Mean MPR <80% considering all drugs.
 Estevez-Cordero RA / Arch Clin Psychiatry. 2021;48(1): 66-68
DISCUSSION
In the present study, the results show that only a small minority
of clozapine treated outpatients (2.7%) had a laxative prescription.
Furthermore, those patients on laxatives did not seem to be taking
them as prescribed, as shown by poor adherence rates (MPR =
8.4%). Patients with prescribed laxative drugs were 12 years older
and were on around three more drugs on average than patients
without laxatives. No difference between groups were found in
clozapine dose, duration of clozapine treatment or anticholinergic
burden. Anyway, the small number of patients on laxatives makes
drawing solid conclusions difficult.
Our findings highlight that awareness of this prevalent and
dangerous adverse reaction is not widespread across prescribers in
Araba, Northern Spain, and that recommendations about starting
prophylactic laxative use in every patient on clozapine are not
followed. Interestingly, adherence was very poor in the six patients
receiving laxatives, with four patients not refilling any laxatives at
all. The proportion of patients with suboptimal adherence to any
drug was also higher in this group. Although MPR is an indirect
method to measure adherence, true adherence will likely be even
lower, since pharmacy refills do not guarantee that the medication
collected was actually swallowed.
Some laxatives are available as over the counter medications
in Spain. Both prescription and over the counter drugs can be
recorded by doctors in PRESBIDE, but over the counter drugs are
not always prescribed. So the proportion of patients taking laxatives
in our study may be underestimated.
Laxatives are excluded from reimbursement in Spain, as occurs
in many countries (other drugs, such as antipsychotics are almost
totally funded by the government, patients paying a maximum of
around €5 per prescription). Although we did not study the reasons
for this non-adherence, we believe having to pay laxatives in full
might have deleterious consequences in clozapine-treated patients.
In conclusion, laxatives appeared to be under-utilized in
clozapine-treated patients in Northern Spain. We recommend
psychiatrists, general practitioners and healthcare professionals
consider offering laxative drugs to all clozapine-treated patients,
explaining the risks of CIGH and reinforcing the importance
of taking laxatives as prescribed. Moreover, we urge healthcare
authorities to consider reimbursement of laxatives in this patient
population.
Key Points
• Laxatives are under-utilized in clozapine treated outpatients in
our setting.
• Patients on laxatives showed poor adherence rates.
• We urge healthcare authorities to consider reimbursement of
laxatives in this patient population.
Conflicts of Interest
The authors declare no conflicts of interest.
68
References
1. Palmer SE, McLean RM, Ellis PM, Harrison-Woolrych M. Life-
threatening clozapine-induced gastrointestinal hypomotility: an analysis
of 102 cases. J Clin Psychiatry. 2008;69:759-68.
2. Food and Drug Administration. Safety Communication. Warning that
untreated constipation caused by schizophrenia medicine clozapine
(Clozaril) can lead to serious bowel problems. Available at: https://www.
fda.gov/drugs/drug-safety-and-availability/fda-strengthens-warning-
untreated-constipation-caused-schizophrenia-medicine-clozapine-
clozaril-can. Accessed [May 4th, 2020].
3. Every-Palmer S, Inns SJ, Ellis PM. Constipation screening in people
taking clozapine: A diagnostic accuracy study. Schizophr Res.
2020;220:179-186.
4. Every-Palmer S, Inns SJ, Grant E, Ellis PM. Effects of Clozapine on the
Gut: Cross-Sectional Study of Delayed Gastric Emptying and Small and
Large Intestinal Dysmotility. CNS Drugs. 2019;33(1):81-91.
5. Every-Palmer S, Nowitz M, Stanley J, et al. Clozapine-treated Patients
Have Marked Gastrointestinal Hypomotility, the Probable Basis of Life-
threatening Gastrointestinal Complications: A Cross Sectional Study.
EBioMedicine. 2016;5:125-34.
6. Every-Palmer S, Ellis PM. Clozapine-Induced Gastrointestinal
Hypomotility: A 22-Year Bi-National Pharmacovigilance Study of
Serious or Fatal 'Slow Gut' Reactions, and Comparison with International
Drug Safety Advice. CNS Drugs. 2017;31(8):699-709.
7. Attard A, Iles A, Attard S, Atkinson N. Clozapine: why wait to start a
laxative? BJPsych Advances. 2019;25(6):1-10
8. Every-Palmer S, Ellis PM, Nowitz M, et al. The Porirua Protocol in
the Treatment of Clozapine-Induced Gastrointestinal hypomotility
and Constipation: A Pre- and Post-Treatment Study. CNS Drugs.
2017;31(1):75-85.
9. Lertxundi U, Hernandez R, San Miguel S, et al. The burden of constipation
in psychiatric hospitals. Int J Psychiatry Clin Pract. 2018;22(2):143-150
10. Yaegashi H, Kirino S, Remington G, Misawa F, Takeuchi H. Adherence
to Oral Antipsychotics Measured by Electronic Adherence Monitoring
in Schizophrenia: A Systematic Review and Meta-analysis. CNS Drugs.
2020;34(6):579-598.
11. Lertxundi U, Hernandez R, Corcostegui B, Ibarra O, Mentxaka G,
Medrano J. Influence of an inconsistent appearance of antipsychotics on
drug adherence in patients with schizophrenia. Medicine (Baltimore).
2018;97(44):e12990.
12. WHO ATC Classification. Available at: https://www.whocc.no/atc_ddd_
index/. Accesed [April 20th, 2020].
13. Rudolph J, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic
risk scale and anticholinergic adverse effects in older persons. Arch
Intern Med. 2008;165:508–513.
14. Boustani MA, Campbell NL, Munger S, Maidment I, Fox GC. Impact of
anticholinergics on the aging brain: a review and practical application.
Aging Health. 2008;4:311–320.
15. Durán CE, Azermai M, Vander Stichele RH. Systematic review of
anticholinergic risk scales in older adults. Eur J Clin Pharmacol.
2013;69(7):1485-96.
16. Velligan DI, Wang M, Diamond P, et al. Relationships among subjective
and objective measures of adherence to oral antipsychotic medications.
Psychiatric Services. 2007;58:1187–1192.

Exacerbation of anxiety symptoms in the setting of COVID-19 pandemic: An overview
and clinically-useful recommendations
Gustavo C Medeiros1
Scott R. Beach2
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
1
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
2
Received: 08-06-2020 – Accepted: 22-08-2020
DOI: 10.1590/0101-60830000000281
Medeiros GC / Arch Clin Psychiatry. 2021;48(1):69-70
The emergence and rapid spread of the coronavirus disease
2019 (COVID-19) have caused dramatic life changes, including
disruption of socioeconomic dynamics, in the setting of measures
to reduce the dissemination of the disease1. The first COVID-19
case was confirmed in November 2019 and, as of June 8, 2020,
the virus had already been isolated from approximately 7,000,000
persons worldwide, leading to more than 400,000 deaths2. Many
countries, including Brazil, still are in the acceleration phase of the
infection. Therefore, it is likely that the pandemic will affect many
more individuals, and it is unclear when more intensive preventive
measures will be no longer recommended.
Evidence from previous outbreaks and initial data from the
COVID-19 pandemic indicate that distressing psychological
responses are frequent in these situations1,3-5. Among them,
excessive anxiety is one of the most common dysfunctional
responses1,3,4. Individuals with psychiatric disorders, particularly
those with anxiety and trauma-related disorders, are at increased
risk for excessive anxiety. Some common symptoms of anxiety
exacerbation are insomnia, irritability/anger, a decreased sense of
safety, difficulty relaxing, restlessness, fatigue, excessive worrying,
and nervousness1,3,5. The following case vignettes illustrate currently
common situations in mental health services.
Case vignette: A 25-year-old woman with generalized anxiety
disorder and posttraumatic stress disorder secondary to physical and
emotional abuse first sought care for psychiatric symptoms about
5 years ago. She had a good response to sertraline and pregabalin
combined with eye movement desensitization and reprocessing
(EMDR). In the 3 months before the outbreak of the COVID-19, the
patient was psychiatrically stable, socially active, and very functional.
In her follow up appointment on March 19, a few days after more
intense measures against COVID-19 were announced in her region,
Address for correspondence: Gustavo C. Medeiros, M.D. , Department of Psychiatry, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX-75390-9119, USA
Phone: +1 214 648 7312; Email: gcmedeiros@live.com
Letter to the editor
she was more much more anxious than usual, and complained of
insomnia, restlessness and occasional tremors. The patient reported
excessive worry with social isolation, and concerns that she will not
be able to refill her medications or to continue her EMDR treatment.
In addition to patients with psychiatric disorders being at
elevated risk for excessive anxiety in the setting of pandemic,
there is some evidence linking other characteristics to more
significant psychological impact and anxiety in response to
COVID-19. They include: 1) female gender3,4, 2) lower household
income3, 3) being a young adult or an elderly person3 (the latter
is a group particularly vulnerable to COVID-19), 4) being a
healthcare worker3, 5) pregnancy3, 6) lower formal educational
level3,4 (potentially due to more difficulty accessing online and
smartphone-based interventions), and 7) living in an area that has
been more substantially affected by the COVID-19 pandemic. It is
not possible to design one-size-fits-all therapeutic interventions,
and customization is needed. However, Table 1 provides some
general guidance.
The negative psychological impact of excessive anxiety might
be felt not only acutely but also long after the pandemic3. Therefore,
facilitating access to evidence-driven mental health care should
be part of the interventions to minimize/manage the impact of
COVID-19. At-risk groups should receive more intensive and
earlier mental health support.
Conflicts of Interest and Source of Funding
Dr. Gustavo C. Medeiros is supported by a National Institute of
Mental Health of the National Institutes of Health under Award
Number R25MH101078. Scott R. Beach have no conflicts of
interests to report. This letter did not have any source of funding.
70 Medeiros GC / Arch Clin Psychiatry. 2021;48(1): 69-70

Table 1. Possible interventions to manage excessive anxiety related to the coronavirus disease 2019 (COVID-19) outbreak.
Anxiety-provoking situation Possible interventions to manage anxiety

- Educate patients using evidence-based and timely data

Inaccurate information and rumors
about the COVID-19 outbreak.
Financial difficulties, which are more
common in those self-employed and/
or those who are unable to take paid
absences.
Separation from loved ones, decreased - Recommend keeping in touch with loved ones through social media, videoconference and phone
socialization and sense of isolation.
Healthcare workers dealing with
patients infected by COVID-19
Fear of acquiring with the virus and/or
infecting others.
Not being able to continue appointments
or to obtain prescriptions
Worsening of family conflicts and
domestic violence, due to increased
time spent with family members
Physical and emotional symptoms of
anxiety might reinforce distress
Frustration and boredom
- Provide reliable sources of information such as the World Health Organization website
- Suggest checking news about the COVID-19 situation no more than 2 times per day
- Politely correct inaccurate information provided by the patient
- Provide information about programs that provide financial assistance
- Recommend reaching persons that the patient trusts such as community or religious leaders
- Provide contact information for crisis hotlines and online support groups
- Provide sources of psychosocial support
- Enhance the sense of purpose
- Utilize meditation.
- Validate that some level of anxiety is understandable
- Make supportive statements without negatively affecting public health interventions
- Educate patients about hands washing, coughing etiquette, face coverings and other preventive interventions
- Nurture altruism
- Establish a plan to continue mental health treatment through telemedicine using phone or video
- If the treatment needs in-person contact (such as eye movement desensitization and reprocessing), consider
temporarily changing to another modality that might be delivered through telemedicine, such as supportive
psychotherapy
- If available, consider home delivery of medications
- Establish safety plans
- Provide phone numbers of domestic violence hotlines
- Recommend physical exercise, relaxation techniques, and/or pharmacological management
- Recommend against the use of alcohol and other drugs to manage acute anxiety symptoms
- Engaging in enjoyable activities and hobbies

References 4. Wang C, Pan R, Wan X, et al. Immediate psychological responses

and associated factors during the initial stage of the 2019 coronavirus
1. Committee I-AS. Briefing note on addressing mental health and
disease (COVID-19) epidemic among the general population in china.
psychosocial aspects of COVID-19 Outbreak -Version 1.0. 2020.
International Journal of Environmental Research and Public Health.
2. University JH. Coronavirus Resource Center. 2020.
2020;17(5):1729.
3. Brooks SK, Webster RK, Smith LE, et al. The psychological impact
5. CTST. Taking Care of Patients During the Coronavirus Outbreak: A
of quarantine and how to reduce it: rapid review of the evidence. The
Guide for Psychiatrists. 2020.
Lancet. 395(10227): 912-920.
 Letter to the Editor

Plasma paroxetine level is independent of the change in plasma interleukin-6 level in

remitted patients with major depressive disorder
Reiji Yoshimura
Naomichi Okamoto
Yuki Konishi
Atsuko Ikenouchi
Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 8078555, Japan

Received: 26/08/2020– Accepted: 17-11-2020

DOI: 10.1590/0101-60830000000282

Yoshimura R / Arch Clin Psychiatry. 2021;48(1):71-72

Keywords: Major depressive disorder; paroxetine; interleukin 6; plasma

To the Editor 70

Plasma paroxetine at week 8(ng/ml)

Several meta-analyses have been reported that plasma interleukin 60
6 (IL-6) concentration is significantly higher in patients with
50
major depressive disorder (MDD) compared with healthy controls.
We previously reported that plasma IL-6 level was associated 40
with responses to antidepressant drugs in patients with MDD1-
30
5. Moreover, we have demonstrated that plasma IL-6 level is

associated with the prefrontal thickness, hippocampal volume, and 20

microstructural changes in the inferior fronto-occipital fasciculus
10
in drug-naïve patients with MDD6,7. From the above findings, it may
be surmised that IL-6 plays a role in the pathophysiology of MDD. 0
Since we previously reported that plasma levels of fluvoxamine, -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1

a selective serotonin reuptake inhibitor (SSRI), did not influence
plasma IL-6 concentrations3, we also investigated a preliminary
study to examine the association between plasma paroxetine,
anther SSRI, and IL-6 concentrations in patients with MDD.
The study protocol and procedures were approved by the Ethics
Committee of the University of Occupational and Environmental
Health, Kitakyushu, Fukuoka, Japan. Written informed consent was
obtained from all subjects. The study participants met the following
criteria: 1) diagnosed with MDD according to the Diagnostic and
Statistical Manual, fifth edition; 2) received paroxetine monotherapy
at least 8 weeks; 3) were considered to be in remission for at least
8 weeks (Hamilton Rating Scale for Depression-17 (HAMD17)
score ≤7) after starting paroxetine monotherapy (mean±standard
deviation=27.1±9.7 mg/day). Eighteen individuals who had been
diagnosed with MDD, but were in remission (men/women, 7/11;
age, 46.4±9.3 years), were enrolled in this study. The HAMD17
score was calculated at baseline and at 8 weeks of initiating
paroxetine therapy (23.3±3.3 and 5.6±1.2, respectively). Blood
sampling was performed twice—before paroxetine treatment and
8 weeks after initiating treatment. The plasma levels of paroxetine
and IL-6 were measured as previously described [5,6]. Plasma IL-6
level did not change before and 8 weeks after paroxetine treatment
(before; 1.41±0.51 pg/mL; at 8 weeks, 1.40±0.29 pg/mL; paired
t-test: p=0.913). Plasma IL-6 level and paroxetine concentrations
showed no correlation at 8 weeks of treatment (Pearson’s correlation
coefficient: r=0.110, p=0.663; Figure 1). We have previously
reported that selective serotonin reuptake inhibitors, including
paroxetine and sertraline, decreased plasma IL-6 level in patients
Delta plasma IL-6 (baseline-week 8) (pg/ml)
Figure 1. Plasma paroxetine concentration and the change in plasma IL-6 level.
with MDD, and that this decline is associated with the implement
of depressive state5. However, the result could not be confirmed
in the patients with MDD treated with paroxetine, but who were
in remission. Moreover, plasma paroxetine level did not influence
plasma IL-6 level, which was in accordance with our previous
results of fluvoxamine3. Thus, the association between the response
to paroxetine, plasma paroxetine level, and plasma IL-6 level should
be further investigated.
Acknowledgement
None.
Conflict of Interest Statement
All authors did not have any conflict of interest to declare.
Funding Sources
None
Author Contributions
RY planned the project and performed as a director, write first daft
and final draft. NO, YK, and AI performed sampling and its assay.

Address for correspondence: Reiji Yoshimura, Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 8078666, Japan, Tel: +81936917253; Fax:
+81936924894; E-mail: yoshi621@med.uoeh-u.ac.jp
72 Yoshimura R / Arch Clin Psychiatry. 2021;48(1): 71-72
References
1. Hiles SA, Baker AL, de Malmanche T, Attia J. A Meta-Analysis of
Differences in IL-6 and IL-10 Between People With and Without
Depression: Exploring the Causes of Heterogeneity. Brain Behav
Immun. 2012;26(7):1180–8.
2. Więdłocha M, Marcinowicz P, Krupa R, Janoska-Jaździk M, Janus M,
Dębowska W, et al. Effect of Antidepressant Treatment on Peripheral
Inflammation Markers - A Meta-Analysis. Prog Neuropsychopharmacol
Biol Psychiatry. 2018 ;80:217–26.
3. Yoshimura R, Katsuki A, Atake K, Hori H, Igata R, Konishi Y. Influence
of Fluvoxamine on Plasma interleukin-6 or Clinical Improvement in
Patients With Major Depressive Disorder. Neuropsychiatr Dis Treat.
2017;13:437–41.
4. Yoshimura R, Kishi T, Iwata N. Plasma Levels of IL-6 in Patients With
Untreated Major Depressive Disorder: Comparison With Catecholamine
Metabolites. Neuropsychiatr Dis Treat. 2019;15:2655–661.
5. Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Katsuki
A, Atake K, et al. Plasma Levels of interleukin-6 and Selective Serotonin
Reuptake Inhibitor Response in Patients With Major Depressive
Disorder. Hum Psychopharmacol. 2013;28(5):466–70.
6. Kakeda S, Watanabe K, Katsuki A, Sugimoto K, Igata N, Ueda I, et al.
Relationship Between Interleukin (IL)-6 and Brain Morphology in
drug-naïve, First-Episode Major Depressive Disorder Using Surface-
Based Morphometry. Sci Rep. 2018;8(1):10054.
7. Sugimoto K, Kakeda S, Watanabe K, Katsuki A, Ueda I, Igata N, et al.
Relationship Between White Matter Integrity and Serum Inflammatory
Cytokine Levels in Drug-Naive Patients With Major Depressive
Disorder: Diffusion Tensor Imaging Study Using Tract-Based Spatial
Statistics. Transl Psychiatry. 2018;8(1):141.

Opercular syndrome in childhood with manic symptoms: a case report
Lee Fu-I1*
https://orcid.org/0000-0002-2176-2464
Miguel Angelo Boarati2
XXXXXXXX
Gustavo Nogueira Lima2
XXXXXXXX
Universidade de Sao Paulo Faculdade de Medicina, Ringgold standard institution – Psiquiatria, Dr Ovidio Pires, de Campos 875 Terreo - Ala Sul , Sao Paulo, SP 05403-903, Brazil
1
University of Sao Paulo Hospital of Clinics Ringgold standard institution, Sao Paulo, São Paulo, Brazil
2
Received: 13/01/2021 – Accepted: 01-02-2021
DOI: 10.1590/0101-60830000000283
Fu-I L / Arch Clin Psychiatry. 2021;48(1):73-74
Keywords: oeprcular syndrome, child, bipolar disorder, neurological development
The Opercular Syndrome, also known as Foix-Chavany-Marie
Syndrome, is characterized by malformation or lesion in the cortical
perisylvian region (the most common being polymicrogyria,
revealed by cranium magnetic resonance imaging - MRI). It displays
several clinical manifestations such as epilepsy, motor deficits,
pseudobulbar palsy, automatic-voluntary dissociation, speech
difficulties, diplegia of masticatory muscles, and mental retardation.
Although psychiatric symptoms are frequently cited, usually limited
to unspecific psychopathological terms like "emotional lability", no
detailed description of the psychiatric feature is available in the
medical literature and rare report in children.
We report the case of a child with Opercular Syndrome who
first presented with hyperactivity and euphoric mood symptoms,
attended to a Child and Adolescence Affective Disorder Program,
from nine to 18 years old.
Case
L, Caucasian, healthy girl, with family history of mood and
substance use disorder. Since 3 years-old, due to psychomotor
agitation, sleep disturbs and appetite complaints was treated with
clonazepam, methylphenidate, sodium valproate, carbamazepine,
oxcarbazepine, and risperidone, without any improvement. At 4
years-old, she also begam present prominent social inadequacy
with disinhibition, learning disabilities, increasing impulsivity and
aggressivity, which led to 3 different schools expelling her.
At 7years-old, she was first referred to our service, and call for
attention the possibility of manic episode due to mood elation,
pressure of speech, severe restlessness, decrease need for sleep,
social inadequacy with disinhibited and hypersexualized behavior.
There was no evidence of previous history of seizures, stroke, or
depressive episodes. The clinical laboratory screening had normal
results.
She initially received lithium carbonate 1050mg daily and
risperidone 6 mg daily without any improvement. Still, no
improvement when replaced lithium with sodium divalproate 1000
mg/day, and nor after replaced risperidone with olanzapine till 30
mg/day. The refractoriness of L. condition to drugs commonly used
to treat mania has led to further investigation. The neurological
assessment revealed pseudo-bulbar facie, mild drooling,
Address for correspondence: Naciye Selcen Bayramci, Department of Bioengineering, Faculty of Engineering and Architecture, Tokat Gaziosmanpasa University, 60250 Tokat, Turkey
Letter to the Editor
craniofacial disproportion and left upper limb dysmetria, raising
the diagnostic hypothesis of Opercular Syndrome. The cranium
MRI showed posterior verticalization of sylvian fissures and
sylvian fissure thickness, compatible with polymicrogyria thought
Opercular Syndrome. The electroencephalography was normal.
Inpatient stay was then made necessary. Significant improvement
was observed after reintroduction of lithium carbonate 750 mg/d
(lithium dosage = 0.9 mEq/L) combined with olanzapine 30 mg/d.
Despite mood stabilization, she kept on persistent hyperactivity
symptoms pattern, then also use additional methylphenidate 10mg
/3 times daily, later, switched to OROS methylphenidate 18mg
once daily, with important hyperactivity improvement. With the
same medications, L. eventually presented hyperthymic, however
continued reasonably stable and remained in follow-up in our
service until she was 18 years old.
Discussion
Several neurological disorders involving cortical and subcortical
brain structures may present with behavior or emotional
manifestation, which is difficult to distinguish from primary
psychiatric disease, especially bipolar disorder
Our patient, due to the persistent euphoric mood, the rapid and
abundant speech pattern and the decreased need for sleep, typical
symptoms of mania, really made it difficult to visualize the primary
neurological manifestations. Manic symptoms were reported as
frequent after brain lesion; however, our patient has been monitored
from nine to 18 y.o. which certainly guarantees that she has not
suffered brain trauma, stroke, or tumor. Thus, the hypothesis of
congenital opercular syndrome appears to be plausible.
The manifestation of emotional instability and psychotic
presentations appears to be common in pediatric neurological
syndrome, but psychiatrists tended to overlook neurological
symptoms in psychiatric patients, and delay to uncover earlier
symptoms of brain structure degenerative.
There is scarce literature regards psychopathological
manifestations of Opercular Syndrome. The reported case
highlights the need for more research on psychiatric symptoms
related to this syndrome and its clinical management.
 74 Fu-I L / Arch Clin Psychiatry. 2021;48(1): 73-74
Previous presentation: The abstract of preliminary findings
has been presented at The New Research Posters of the International
Society of Bipolar Disorder (ISBD) Annual Meeting in New Delhi,
28th January, 2008.
Potential conflicts of interest: The authors report no financial
or other relaship relevant to the subject of this article.
Funding/Support: None
References
1. Mendez MF. Mania in neurologic disorders. Curr Psychiatry Rep.
2000;2(5):440-5.
2. Craney JL, Geller B. A prepubertal and early adolescent bipolar
disorder-I phenotype: review of phenomenology and longitudinal
course. Bipolar Disorder. 2003;5(4):243-56.
3. Teixeira KC, Montenegro MA, Cendes F, Guimarães CA, Guerreiro
CA, Guerreiro MM. Clinical and electroencephalographic features of
patients with polymicrogyria. J Clin Neurophysiol. 2007;24(3):244-51.
4. Luat AF, Bernardi B, Chugani HT. Congenital perisylviansyndrome:
MRI and glucose PET correlations.PediatrNeurol. 2006;35(1):21-9.
5. Praveen-Kumar S, Pramod K. Bi-opercular Syndrome: A Case Report
and Minireview. J Clin Diagn Res. 2014;8(6):MD03-4.
6. Satzer D, Bond DJ. Mania secondary to focal brain lesions: implications
for understanding the functional neuroanatomy of bipolar disorder.
Bipolar Disord. 2016;18(3):205-20.
7. Braden RO, Leventer RJ, Jansen A, Scheffer IE, Morgan AT. Speech and
language in bilateral perisylvian polymicrogyria: a systematic review.
Dev Med Child Neurol. 2019;61(10):1145-1152.