International Review of Psychiatry

ISSN: 0954-0261 (Print) 1369-1627 (Online) Journal homepage: https://www.tandfonline.com/loi/iirp20

From dysthymia to treatment-resistant

depression: evolution of a psychopathological
construct

Antonio Ventriglio, Dinesh Bhugra, Gaia Sampogna, Mario Luciano,

Domenico De Berardis, Gabriele Sani & Andrea Fiorillo

To cite this article: Antonio Ventriglio, Dinesh Bhugra, Gaia Sampogna, Mario Luciano, Domenico
De Berardis, Gabriele Sani & Andrea Fiorillo (2020): From dysthymia to treatment-resistant
depression: evolution of a psychopathological construct, International Review of Psychiatry, DOI:
10.1080/09540261.2020.1765517

To link to this article: https://doi.org/10.1080/09540261.2020.1765517

Published online: 21 May 2020.

Submit your article to this journal

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=iirp20
INTERNATIONAL REVIEW OF PSYCHIATRY
https://doi.org/10.1080/09540261.2020.1765517

REVIEW ARTICLE

From dysthymia to treatment-resistant depression: evolution of a

psychopathological construct
Antonio Ventriglioa , Dinesh Bhugrab , Gaia Sampognac, Mario Lucianoc ,
Domenico De Berardisd , Gabriele Sanie and Andrea Fiorilloc
a
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; bInstitute of Psychiatry, Psychology and
Neuroscience, King’s College London, London, UK; cDepartment of Psychiatry, University of Campania “L. Vanvitelli”, Naples, Italy;
d
Department of Mental Health, ASL Teramo, Teramo, Italy; eDepartment of Neuroscience, Section of Psychiatry, Universit
a Cattolica
del Sacro Cuore, Rome, Italy

ABSTRACT ARTICLE HISTORY

Dysthymia is a psychopathological construct historically described and often reconsidered Received 1 April 2020
through the centuries. Its first description is dated back to 400 b.C., when Hippocrates proposed Accepted 1 May 2020
his theory about the ‘black bile’ and the melancholic temperament. The concept of dysthymia
KEYWORDS
(dys-, ‘ill’, thymia-, ‘emotions’) has been largely elaborated in the XIX and XX centuries by
Dysthymia; dysthymic
Burton, Cullen, Schneider, Kretschmer, Akiskal and other authors, and recently re-formulated in disorder; persistent
the various editions of the modern Diagnostic and Statistical Manual of Mental Disorders under depressive disorder;
different diagnostic labels: neurotic depression, dysthymic disorder, persistent depressive dis- treatment- resist-
order. Beyond the nosology, dysthymia issues some other challenges, including the need for fur- ant depression
ther research to characterise the peculiar pathophysiological framework of this syndrome
(compared with major depressive disorder) and to better define evidences about tailored-treat-
ment options and their effectiveness.

Historical background published from 1624 to 1651), suggested that melan-

The term Dysthymia derives from the ancient Greek
‘dys-’, meaning ‘ill’ or ‘bad’, and ‘-thymia’, meaning
‘emotions’. Etymologically, it refers to a chronic, per-
sistent, lifetime, mild state of depression. Hippocrates
of Kos, ‘The Father of Medicine’ (460–370 b.C.),
described individuals who were worried, insecure,
lethargic as well as characterised by a melancholic
temperament, probably due to an intoxication of
‘black bile’, one of the four primary ‘humours’, as con-
ceptualised in the ‘Theory of Four Humours’: he
postulated that an excess of one of these humours
(black bile, yellow bile, blood, phlegm) might bring to
a specific temperament in humans (Akiskal, 2001).
Dysthymia has been included in the concept of mel-
ancholia for centuries. The melancholic temperament
has been described by several authors - particularly
Avicenna (980–1037), Maimonides (1135), Averrois
(1126), Constantine (1019–1087) among the others -
as characterised by symptoms of chronic depression,
or phobia or paranoia (Cordas, 2002). In 1621 Robert
Burton, in his book ‘Anatomy of Melancholy’ (re-
choly was probably due to an advanced age, heredity
and temperament, and it might also lead to phys-
ical diseases.
William Cullen (1710–1790), in his ‘First Lines of
Practice of Physic’ (1786), considered melancholy an
instability of the brain (mood) with ‘higher degrees of
mania which melancholia so often passes into’, as later
recognised by Jules Baillarger (1809–1890) and Jean-
Pierre Falret (1794–1870) in their descriptions of a
new form of mood instability, that they called ‘la folie

a double forme’ or ‘folie circulaire’ (Brieger &
Marneros, 1997; Pichot, 2004). In 1863, K.L.
Kahlbaum used the terms ‘cyclothymia’ for describing
those forms of mood instability and fluctuations, and
‘dysthymia’ for referring to a prevalent state of attenu-
ated depression.
In 1921, Emil Kraepelin proposed a dichotomous
classification of mental illnesses into ‘Dementia
Praecox’ and ‘Maniac-Depressive Insanity’, suggesting
that the depressive temperament belonged to the
manic-depressive insanity (called ‘Konstitution’) con-
stellation in a continuum model, whose characteristics

CONTACT Antonio Ventriglio a.ventriglio@libero.it Department of Clinical and Experimental Medicine, University of Foggia, presso Ospedali Riuniti
di Foggia, Foggia, 71121, Italy.
ß 2020 Institute of Psychiatry and Johns Hopkins University
2 A. VENTRIGLIO ET AL.
were persistent sadness (although fluctuating), pessim-
ism and lack of pleasure (called ‘Verstimmung’)
(Angst, 2002).
Kurt Schneider in his book on psychopathic per-
sonalities (1923) described two different forms of
depressive conditions, namely melancholic and react-
ive ones. He suggested that depressive psychopathy
(melancholic form) was due to an interaction between
hereditary and early environmental variables, not
referring to a proper depressive disease (considered,
instead, as a reactive form). Definitely, Schneider
described depressive psychopathy as a constitutional
abnormal variation of personality.
Also, Ernst Kretschmer in his book Physique and
Character (1931) reinforced the concept of an existing
continuum between constitution (including body
shape) and basic temperament with possible preva-
lence of depressive personality traits. According to
this reconceptualization of dysthymic disorder, in
1983 Akiskal and Tellenbach-Kraus proposed two
psychopathological constructs, called ‘Neurotic
Depression’ and ‘Typus Melancholicus’, respectively
(Akiskal, 1983; Ambrosini et al., 2011). Akiskal devel-
oped a nosological framework of ‘low-grade chronic
depressions’, including early-onset characterological
depressions, such as subaffective dysthymic disorders,
conceptualised as a constitutional attenuated form of
primary affective illness. Akiskal’s construct of
‘Neurotic Depression’ includes: (a) general distress, (b)
negative emotions, especially sadness, irritability, dis-
appointment, futility, (c) anxiety or agitation, (d) low
self-esteem, (e) mild social impairment. Similarly, the
Typus Melancholicus proposed by Tellenbach-Kraus is
considered the construct of a premorbid personality-
structure, which is highly vulnerable to melancholy.
The operational criteria for describing this psycho-
pathological construct are (a) concern with orderli-
ness, fixation on the harmony of the interpersonal
relationships; (b) conscientiousness, need to prevent
feelings and attributions of guilt; (c) hyper/eterono-
mia, exaggerated adaption to the rules and exagger-
ated receptivity to external rules; (d) intolerance of
ambiguity, inability to emotionally and cognitively
perceive opposite characteristics in relation to a same
object, person or situation.
Both these proposals, in line with the Schneiderian
concepts, led the modern Diagnostic and Statistical
Manual of Mental Disorders (DSM) and International
Classification of Diseases (ICD) to consider such
forms of chronic depression as part of temperamental
neuroses, somewhat linked to personality disorders
(Nardi et al., 1993; Spanemberg & Juruena, 2004).
Modern challenges
Nosology
It is a modern challenge in psychiatry to define the
threshold between common sadness, depressive per-
sonality traits and clinically-relevant levels of depres-
sion (Palma & Pancheri, 2000; Wakefield & Schmitz,
2013). In 1991, Siever & Davis proposed a continuum
model including clinically isolated depressive symp-
toms (such as sadness), sub-threshold depressive con-
ditions as well as clinically- defined major
depressive states.
In 1997, Angst & Merikangas proposed the term
‘threshold psychiatry’ referring to the depressive spec-
trum as a larger construct of depressive states ranging
from adjustment disorders with depressed mood to
minor and major depression. In 1968, the DSM-II
(APA) included the construct of ‘Neurotic Depression’
and the ICD-9 included ‘Depressive Neuroses’ among
the non-chronic episodes of depression.
In 1980, the DSM-III proposed the concept of
chronic (and neurotic) depression with the new label
of ‘Dysthymic Disorder’ (APA, 1980; Kocsis &
Frances, 1987; Torgersen, 1986). Despite the atheor-
etical model inspiring the newer version of the diag-
nostic manual, the task force of DSM-III approved
the removal of chronic depression from the domain
of character and personality disorders: dysthymic
disorder included both primary depressions with
residual chronicity as well as character-based depres-
sions (personality disorders) (APA, 1980; Kocsis &
Frances, 1987; Torgersen, 1986). The DSM-III-R
(APA, 1987) and the DSM-IV (APA, 1994) incorpo-
rated these definitions, and the Depressive Personality
Disorder has been proposed in the research section
of DSM-IV (APA, 1987; , 1994). In the Text
Revision of DSM-IV (DSM-IV TR; APA, 2000), the
Dysthymic Disorder diagnostic criteria included
depressed mood for most of the day for more days
for at least 2 years, and two of the following symp-
toms: (1) poor appetite or overeating; (2) insomnia
or hypersomnia; (3) low energy or fatigue; (4) low
self esteem; (5) poor concentration or difficulty mak-
ing decisions; and (6) feelings of hopelessness. Also,
during the first 2 years after the onset, episodes of
major depression were excluded. In the Appendix B
of the DSM-IV-TR (APA, 2000), the construct of
depressive personality disorder, controversially over-
lapping with dysthymic disorder, included five or
more of the following symptoms: (1) usual mood is
dominated by dejection, gloominess, cheerlessness,
joylessness and unhappiness; (2) self-concept centred

on beliefs of inadequacy, worthlessness and low self-
esteem; (3) the patient is critical, blaming and
derogatory towards the self; (4) the patient is brood-
ing and worried; (5) the patient is negativistic, crit-
ical and judgmental towards others; (6) the patient
is pessimistic; (7) the patient is prone to feeling
guilty or remorseful (Ryder et al., 2002).
In the DSM-5 (fifth edition; APA, 2013), the term
Persistent Depressive Disorder represents what was
previously labelled as dysthymia and chronic major
depression. According to the manual, the patient
must present a depressed mood for at least 2 years.
For children or adolescents, the mood can be also
irritable or depressed for at least 1 year. Also, two of
the following symptoms are included: (1) Poor appetite
or overeating; (2) Insomnia or hypersomnia; (3) Low
energy/fatigue; (4) Low self-esteem; (5) Poor concen-
tration/decision making; (6) Hopelessness. The ICD-10
did not define a concept of dysthymia essentially dif-
ferent from depressive neurosis or neurotic depression
(Freeman, 1994; World Health Organization, 2004).
It is of interest that two subtypes of dysthymia
have been recognised over the last decades. In par-
ticular, Niculescu & Akiskal in 2001 proposed (1)
‘anxious dysthymia’, characterised by low self-esteem,
insecurity, anxiety (overlapping with mild bipolar dis-
order) and positively responding to anxiolytics and
selective serotonin reuptake inhibitors; (b) and
‘anergic dysthymia’, characterised by low energy, low
reactivity and anhedonia.
The prevalence of dysthymia or dysthymic disorder
widely varies across different settings, ranging from
3.7% to 20.6% in the primary care settings, or from
3.1% to 6.4% in the large US Epidemiological
Catchment Area Study (Kessler et al., 1994; Sansone
& Sansone, 2009). Also, it has been reported a sex
ratio females/males of 2:1 (Kessler et al., 1994;
Sansone & Sansone, 2009). Recently, Carta et al.
(2019) investigated the lifetime prevalence of the
DSM-5 construct of Persistent Depressive Disorder and
found it ranging from 3% to 6% in Western coun-
tries, with an associated significant impairment of
patients’ quality of life.
In addition, according to some long-term studies
based on 5–10 years of follow-up, the rate of suicide
and suicidal attempts ranges from 19% (Klein et al.,
2000) to 31.7% (Klein e al., 2008) among patients
with dysthymia. Hellerstein et al. (2010) reported a
lower psychosocial functioning among patients with
dysthymic disorder compared to major depression
patients as well as the general population in the
INTERNATIONAL REVIEW OF PSYCHIATRY 3
NESARC study (The National Epidemiologic Survey
of Alcoholism and Related Conditions).
It is of note that dysthymic disorder is largely asso-
ciated with a number of psychiatric comorbidities in
the real world (Sansone & Sansone, 2009), including
major depression (this comorbidity is also known as
double-depression), anxiety disorders, substances abuse,
personality disorders, somatoform disorders (Klein
et al., 2000; Sansone & Correll, 2005). Several clinical
reports confirm that comorbidity between dysthymia
and other syndromes leads to worse clinical outcomes
of all comorbid conditions with higher treatment
resistance, in particular with major depression and per-
sonality disorders (Hellerstein et al., 2010).
Double depression is a common comorbidity refer-
ring to the co-existence of persistent depressive dis-
order (as defined in the DSM-5, which includes the
old concept of dysthymia) and major depressive dis-
order (Keller & Shapiro, 1982). Research and clinical
reports confirm that double depression cannot be con-
sidered as a distinct disorder, even if it shows a more
severe outcome than either major depression or per-
sistent depressive disorder alone, with a higher num-
ber of relapses and a poor response to
pharmacological treatments (Dixon & Thyer, 1998;
Keller & Shapiro, 1982; Parker & Malhi, 2019). The
prevalence of double depression ranges from 2.2% to
26% (Goldney & Fisher, 2004; Keller & Shapiro,
1982). As already discussed, dysthymia and double
depression both show poorer social- and functioning-
recovery rates than major depression alone; comorbid
somatic disorders and neuroticism have been identi-
fied as associated factors for a poorer social and psy-
cho-physical functioning (Rhebergen et al., 2010).
The high rate of psychiatric comorbidity and the
clinical overlapping with other clinical conditions
(also the physical ones), as well as the ‘softness’ of
symptoms, especially at onset, contribute to misdiag-
nosis or late recognition of dysthymia in real-world
settings (Sansone & Sansone, 2009).
Pathophysiology
The identification of biological correlates of dys-
thymia is another challenge to be addressed. It has
been largely documented that chronic depression is
associated with a variety of mono-aminergic transmis-
sion abnormalities (involving a reduction of the levels
of serotonin, norepinephrine and dopamine) in the
human central nervous system (Griffiths et al., 2000).
Also, abnormal neuro-endocrine responses, including
4 A. VENTRIGLIO ET AL.
alterations in the thyroid and hypothalamic-pituitary-
adrenal axis (HPA axis), such as phenotypic variations
of corticotropin releasing hormone and arginine vaso-
pressin with down-regulation of adrenal functioning,
have been found in patients with depressive illness
(Griffiths et al., 2000). Some other studies have shown
lower platelet monoamino-oxidase activity among
patients with dysthymia, especially women (Sansone
& Sansone, 2009). A genetic vulnerability has been
found in the aetiological model of dysthymia through
the evidence of an increased risk of depression occur-
ring among all relatives of unipolar depressive
patients, relatives of dysthymic patients and those
affected by double depression (Griffiths et al., 2000;
Riso et al., 1996). In addition, a number of psycho-
social factors may interact with the genetic back-
ground, such as stress in childhood and adulthood
and unfavourable social circumstances (Sansone &
Sansone, 2009).
Specifically, Akiskal et al. (1984) reported changes
in sleep architecture among patients with dysthymia
with shortened REM (rapid eye movement) latencies,
and an excessive and anomalous distribution of REM-
stages during the early part of the night. Some other
reports have shown that chronic depressive illness is
accompanied by an immune dysregulation, with varia-
tions of circulating cytokine levels (including interleu-
kin-2, IL-2 receptors; interleukin-1 and interleukin-1
receptor antagonist, interleukin-6 and its receptor, g-
interferon) (Griffiths et al., 2000).
Ravindran et al. (2009) proposed a model of
‘functional neuroanatomy’ of dysthymia, based on
functional magnetic resonance imaging studies. The
authors concluded that prefrontal cortex, anterior cin-
gulate, amygdale and insula are involved in the
neuro-physio-anatomic circuit of chronic depressed
mood. Similarly, Lyoo et al. (2002) reported an over-
activation of amygdala (associated with the processing
of negative emotions), an increased activity of the
insula (processing sad emotions) and in the cingulate
gyrus (bridging attention and emotions).
Treatment
Undoubtedly, treatment options for dysthymia and, in
general, for chronic depression are one of the big
unmet needs nowadays. The concept of persistent and
resistant depression may be seen in the same light. In
their detailed review of literature, Griffiths et al.
(2000) reported on the efficacy of antidepressant and
antipsychotic treatments in treating dysthymia: they
reported that most drugs, in particular tricyclic
agents, fluoxetine, sertraline, venlafaxine, amisulpride,
are superior to placebo in improving the quality of
mood, in particular the rate of response ranged
between 61% and 73%. The duration of pharmaco-
therapy is not well established, even if life-long treat-
ments might be suggested in dysthymia (Sansone &
Sansone, 2009, Carta et al., 2019).
In addition to pharmacological treatments, psycho-
therapy has been found to be helpful; in particular, cog-
nitive-behavioral analysis system of psychotherapy
(CBASP), interpersonal psychotherapy (IPT), cogni-
tive-behavioral therapy, and problem-solving therapy
are fully recommended (Carta et al., 2019; Griffiths
et al.,2000; Sansone & Sansone, 2009). Cuijpers et al.
(2008) in their meta-analysis concluded that at least 18
treatment sessions are needed to obtain effective results
with psychotherapies among patients with dysthymic
disorder, even if psychotherapies are not superior to
antidepressant treatments in terms of effectiveness.
Although the modern innovations in the treatment
of chronic depression, the rate of non- responsiveness
among patients with chronic depression is still high,
and a number of residual symptoms are observed also
after long-term treatments (Conradi et al., 2011). The
term Treatment–Resistant Depression has been coined
for characterising those forms of chronic depression
with residual long-term symptoms and high level of
treatment-resistance (Thase & Rush, 1997).
Carter et al. in this issue will report on the relative
effectiveness of augmentation treatments for depres-
sion in a systematic review and meta-analysis, as an
ideal continuum from dysthymia to treatment-resist-
ant depression (RTD).
Disclosure statement
No potential conflict of interest was reported by
the author(s).
ORCID
Antonio Ventriglio http://orcid.org/0000-0002-
3934-7007
Dinesh Bhugra http://orcid.org/0000-0002-0613-2480
Mario Luciano http://orcid.org/0000-0002-4338-1371
Domenico De Berardis http://orcid.org/0000-0003-
4415-5058
Gabriele Sani http://orcid.org/0000-0002-9767-8752
Andrea Fiorillo http://orcid.org/0000-0002-6926-0762
References
Akiskal, H. S. (1983). Dysthymic disorder: Psychopathology
of proposed chronic depressive subtypes. The American

Journal of Psychiatry, 140(1), 11–20. https://doi.org/10.
1176/ajp.140.1.11
Akiskal, H. S. (2001). Dysthymia and cyclothymia in psy-
chiatric practice a century after Kraepelin. Journal of
Affective Disorders, 62(1–2), 17–31. https://doi.org/10.
1016/S0165-0327(00)00347-5
Akiskal, H. S., Lemmi, H., Dickson, H., King, D.,
Yerevanian, B., & Van Valkenburg, C. (1984). Chronic
depressions. Part 2. Sleep EEG differentiation of primary
dysthymic disorders from anxious depressions. Journal of
Affective Disorders, 6(3–4), 287–295. https://doi.org/10.
1016/S0165-0327(84)80007-5
Ambrosini, A., Stanghellini, G., & Langer, A. I. (2011).
Typus melancholicus from tellenbach up to the present
day: A review about the premorbid personality vulner-
able to melancholia. Actas Espanolas de Psiquiatria,
39(5), 302–311.
American Psychiatric Association (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). APA
Publishing.
American Psychiatric Association. (1968). Diagnostic and
statistical manual of mental disorders (2nd ed.). APA
Publishing.
American Psychiatric Association. (1980). Diagnostic and
statistical manual of mental disorders (3rd ed.). APA
Publishing.
American Psychiatric Association. (1987). Diagnostic and
statistical manual of mental disorders (3rd ed., Revised).
APA Publishing.
American Psychiatric Association. (1994). Diagnostic and
statistical manual of mental disorders (4th ed.). APA
Publishing.
American Psychiatric Association. (2000). Diagnostic and
statistical manual of mental disorders (IV ed., Text
Revision ed.). APA Publishing.
Angst, J. (2002). Historical aspects of the dichotomy
between manic-depressive disorders and schizophrenia.
Schizophrenia Research, 57(1), 5–13. https://doi.org/10.
1016/S0920-9964(02)00328-6
Angst, J., & Merikangas, K. (1997). The depressive spec-
trum: Diagnostic classification and course. Journal of
Affective Disorders, 45(1–2), 31–40. https://doi.org/10.
1016/S0165-0327(97)00057-8
Brieger, P., & Marneros, A. (1997). Dysthymia and cyclo-
thymia: Historical origins and contemporary develop-
ment. Journal of Affective Disorders, 45(3), 117–126.
https://doi.org/10.1016/S0165-0327(97)00053-0
Burton, R. (1621). Anatomy of melancholy. British Library.
Carta, M. G., Paribello, P., Nardi, A. E., & Preti, A. (2019).
Current pharmacotherapeutic approaches for dysthymic
disorder and persistent depressive disorder. Expert
Opinion on Pharmacotherapy, 20(14), 1743–1754. https://
doi.org/10.1080/14656566.2019.1637419
Conradi, H. J., Ormel, J., & de Jonge, P. (2011). Presence of
individual (residual) symptoms during depressive epi-
sodes and periods of remission: A 3-year prospective
study. Psychological Medicine, 41(6), 1165–1174. https://
doi.org/10.1017/S0033291710001911
Cordas, T. A. (2002). Depress~ao: da bile negra aos neuro-
transmissores — uma introduç~ao historica. Lemos
Editorial.
INTERNATIONAL REVIEW OF PSYCHIATRY 5
Cuijpers, P., van Straten, A., Andersson, G., & van Oppen,
P. (2008). Psychotherapy for depression in adults: A
meta-analysis of comparative outcome studies. Journal of
Consulting and Clinical Psychology, 76(6), 909–902.
https://doi.org/10.1037/a0013075
Cullen, W. (1786). First lines of the practice of physic. Bell
& Bradfute, and William Creech.
Dixon, D. R., & Thyer, B. A. (1998). Double depression in
men: Does it exist? Journal of Psychopathology and
Behavioral Assessment, 20(2), 187–198. https://doi.org/10.
1023/A:1023030431552
Freeman, H. L. (1994). Historical and nosological aspects of
dysthymia. Acta Psychiatrica Scandinavica, 89(s383),
7–11. https://doi.org/10.1111/j.1600-0447.1994.tb05877.x
Goldney, R. D., & Fisher, L. J. (2004). Double depression in
an Australian population. Social Psychiatry and
Psychiatric Epidemiology, 39(11), 921–926. https://doi.
org/10.1007/s00127-004-0832-7
Griffiths, J., Ravindran, A. V., Merali, Z., & Anisman, H.
(2000). Dysthymia: A review of pharmacological and
behavioral factors. Molecular Psychiatry, 5(3), 242–261.
https://doi.org/10.1038/sj.mp.4000697
Hellerstein, D. J., Agosti, V., Bosi, M., & Black, S. R.
(2010). Impairment in psychosocial functioning associ-
ated with dysthymic disorder in the NESARC study.
Journal of Affective Disorders, 127(1–3), 84–88. https://
doi.org/10.1016/j.jad.2010.04.013
Kahlbaum, K. L. (1863). Die Gruppierung der psychischen
Krankheit und die Einteilung der Seelenst€orung. Verlag
von A. W. Kafemann.
Keller, M. B., & Shapiro, R. W. (1982). “Double
depression”: Superimposition of acute depressive epi-
sodes on chronic depressive disorders. The American
Journal of Psychiatry, 139(4), 438–442. https://doi.org/10.
1176/ajp.139.4.438
Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B.,
Hughes, M., Eshleman, S., Wittchen, H. U., & Kendler,
K. S. (1994). Lifetime and 12-month prevalence of DSM-
III-R psychiatric disorders in the United States from the
National Comorbidity Survey. Archives of General
Psychiatry, 51(1), 8–19. https://doi.org/10.1001/archpsyc.
1994.03950010008002
Klein, D. N., Schwartz, J. E., Rose, S., & Leader, J. B.
(2000). Five-year course and outcome of dysthymic dis-
order: A prospective, naturalistic follow-up study. The
American Journal of Psychiatry, 157(6), 931–939. https://
doi.org/10.1176/appi.ajp.157.6.931
Kocsis, J. H., & Frances, A. J. (1987). A critical discussion
of DSM-III dysthymic disorder. The American Journal of
Psychiatry, 144(12), 1534–1542. https://doi.org/10.1176/
appi.ajp.2010.10070983
Kretschmer, E. (1931). Physique and character.
International Library of Psychology.
Lyoo, I. K., Kwon, J. S., Lee, S. J., Han, M. H., Chang, C.-
G., Seo, C. S., Lee, S. Ik., & Renshaw, P. F. (2002).
Decrease in genu of the corpus callosum in medication-
naïve, early-onset dysthymia and depressive personality
disorder. Biological Psychiatry, 52(12), 1134–1143.
https://doi.org/10.1016/S0006-3223(02)01436-1
Nardi, A. E., Saboya, E., Pinto, S., Figueira, I., Marques, C.,
& Mendlowicz, M. (1993). Distimia: aspectos clınicoter-
ap^euticos. Jornal Brasileiro de Psiquiatria, 42(7), 357–372.
6 A. VENTRIGLIO ET AL.
Niculescu, A. B., III., & Akiskal, H. S. (2001). Proposed
endophenotypes of dysthymia: Evolutionary, clinical and
pharmacogenomic considerations. Molecular Psychiatry,
6(4), 363–366. https://doi.org/10.1038/sj.mp.4000906
Palma, A. P., & Pancheri, P. (2000). Theoretical constructs
and clinical-experimental objectivity of therapeutic inter-
vention in Minor, “Sub-clinical Symptomatic” or “Sub-
syndromal” depressions. Giornale Italiano di
Psicopatologia 6(4).
Parker, G., & Malhi, G. S. (2019). Persistent depression:
Should such a DSM-5 diagnostic category persist?
Canadian Journal of Psychiatry. Revue canadienne de psy-
chiatrie, 64(3), 177–179. https://doi.org/10.1177/
0706743718814429
Pichot, P. (2004). Circular insanity, 150 years on. Bulletin
de l’Academie nationale de medecine, 188(2), 275–284.
https://doi.org/10.1016/S0001-4079(19)33801-4
Ravindran, A. V., Smith, A., Cameron, C., Bhatla, R.,
Cameron, I., Georgescu, T. M., & Hogan, M. J. (2009).
Toward a functional neuroanatomy of dysthymia: A
functional magnetic resonance imaging study. Journal of
Affective Disorders, 119(1–3), 9–15. https://doi.org/10.
1016/j.jad.2009.03.009
Rhebergen, D., Beekman, A. T., de Graaf, R., Nolen, W. A.,
Spijker, J., Hoogendijk, W. J., & Penninx, B. W. (2010).
Trajectories of recovery of social and physical function-
ing in major depression, dysthymic disorder and double
depression: A 3-year follow-up. Journal of Affective
Disorders, 124(1–2), 148–156. https://doi.org/10.1016/j.
jad.2009.10.029
Riso, L. P., Klein, D. N., Ferro, T., Kasch, K. L., Pepper,
C. M., Schwartz, J. E., & Aronson, T. A. (1996).
Understanding the comorbidity between early-onset dys-
thymia and cluster B personality disorders: A family
study. The American Journal of Psychiatry, 153(7),
900–906. https://doi.org/10.1176/ajp.153.7.900
Ryder, A. G., Bagby, R. M., & Schuller, D. R. (2002). The
overlap of depressive personality disorder and dysthymia:
A categorical problem with a dimensional solution.
Harvard Review of Psychiatry, 10(6), 337–352. https://doi.
org/10.1080/10673220216230
Sansone, R. A., & Correll, T. (2005). Dysthymic disorder:
The persistent depression. Hospital Physician Board
Review Man, 9, 1–12.
Sansone, R. A. A., & Sansone, L. A. (2009). Dysthymic dis-
order: Forlorn and overlooked? Psychiatry (Edgemont),
6(5), 46–50.
Schneider, K. (1923). Die psychopathischen Pers€onlichkeiten
oder der Seelenst€orungen und ihrer Behandlung. F.
Deuticke. 96 S., Erstdruck.
Siever, L. J., & Davis, K. L. (1991). A psychobiological per-
spective on the personality disorders. The American
Journal of Psychiatry, 148(12), 1647–1658. https://doi.org/
10.1176/ajp.148.12.1647
Spanemberg, L., & Juruena, M. F. (2004). Dysthymia:
Historical/nosological characteristics and its relationship
with major depressive disorder. Revista de Psiquiatria do
Rio Grande do Sul, 26(3), 300–311. https://doi.org/10.
1590/S0101-81082004000300007
Thase, M. E., & Rush, A. J. (1997). When at first you don’t
succeed: sequential strategies for antidepressant nonres-
ponders. Journal of Clinical Psychiatry, 58 (Suppl 13),
23–29.
Torgersen, S. (1986). Neurotic depression and DSM-III.
Acta psychiatrica Scandinavica. Supplementum,
328(Suppl), 31–34. https://doi.org/10.1111/j.1600-0447.
1986.tb10521.x
Wakefield, J. C., & Schmitz, J. M. F. (2013). When does
depression become a disorder? Using recurrence rates to
evaluate the validity of proposed changes in major
depression diagnostic thresholds. World Psychiatry:
Official Journal of the World Psychiatric Association
(WPA), 12(1), 44–52. https://doi.org/10.1002/wps.20015
World Health Organization. (2004). ICD-10: International
statistical classification of diseases and related health prob-
lems (tenth revision, 2nd ed.). World Health
Organization.