Journal of Affective Disorders 250 (2019) 21–25

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Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Research paper

Risk of attempted suicide among adolescents and young adults with T

traumatic brain injury: A nationwide longitudinal study
Hsuan-Kan Changa,b,c, Ju-Wei Hsud,e, Jau-Ching Wua,b,f, Kai-Lin Huangd,e, Huang-Chou Changg,
Ya-Mei Baid,e, Tzeng-Ji Chenh,i, Mu-Hong Chend,e,
⁎

a
Department of Neurosurgery, Neurologic Institute, Taipei Veterans General Hospital, Taipei, Taiwan
b
School of Medicine, National Yang-Ming University, Taipei, Taiwan
c
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
d
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
e
Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
f
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
g
Department of Surgery and School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
h
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
i
Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan

ARTICLE INFO ABSTRACT

Keywords: Background: Traumatic brain injury (TBI) and suicidal behavior lead to serious morbidity and premature mor-
Suicide tality. TBI in adulthood is associated with a higher incidence of suicide, but the risk in adolescents and young
Adolescent adults is not clear.
Traumatic brain injury (TBI) Methods: Longitudinal follow-up data were extracted from a National Health Insurance Research Database.
National Health Insurance Research Database
Adolescents and young adults (12–29 years old) with and without TBI (1:4) were included, and the incidences of
(NHIRD)
Psychiatric comorbidities
following attempted suicide were analyzed. The association of TBI severity, repeated TBI, and comorbid psy-
chiatric disorders with attempted suicide were also investigated.
Results: Overall, 31,599 and 126,396 subjects were enrolled in the TBI and control cohorts, respectively. The
overall incidence of attempted suicide was significantly higher in the TBI cohort than in the control cohort (4.6%
versus 1.0%, P < 0.001). The age at first suicide attempt was also lower in the TBI cohort (25.71 ± 5.25 versus
28.99 ± 5.26 years, P < 0.001). After adjusting for confounding factors, severe TBI, repeated TBI, female,
younger age at TBI, and comorbid psychiatric conditions (unipolar depression, bipolar disorder, alcohol and
substance use disorders) were associated with higher risks of attempted suicide. Long-term cumulative risks of
attempted suicide were significantly elevated in the TBI cohort (P < 0.001).
Limitation: Access to individual's detailed medical record was not available.
Conclusion: TBI is associated with an elevated risk of attempted suicide in adolescents and young adults. TBI
severity, repetitive injury, female, younger age at injury, and certain psychiatric comorbidities are independent
risk factors.

1. Introduction
Suicide is one of the major causes of premature mortality in ado-
lescents and young adults (Ortega et al., 2012). Suicide is the leading
cause of death in individuals aged 25–44 years in the United States and
is a major public health concern in various countries (Gardner et al.,
1996). The premature mortality and the predisposition factors in young
adulthood must be researched because suicide inflicts profound pro-
ductivity losses and socioeconomic impacts. Early recognition of the
risk factors and prevention of suicide are critical topics in child and
adolescent mental health (Ahern et al., 2018; King et al., 2017).
Traumatic brain injury (TBI) is one of the leading causes of dis-
ability and dependence for daily activities (Jourdan et al., 2016). Pa-
tients who sustain TBI generally suffer from deficits in cognition, at-
tention, memory, and execution. Dramatic changes in personality and
behavior patterns after TBI often harm the patient's family life, social
functioning, and quality of life (Azouvi et al., 2017; Benedictus et al.,
2010). Long-term research has demonstrated that TBI events during

⁎
Corresponding author at: Department of Psychiatry, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, 11217, Taipei, Taiwan.
E-mail address: kremer7119@gmail.com (M.-H. Chen).

https://doi.org/10.1016/j.jad.2019.02.059
Received 15 November 2018; Received in revised form 15 January 2019; Accepted 25 February 2019
Available online 26 February 2019
0165-0327/ © 2019 Elsevier B.V. All rights reserved.
H.-K. Chang, et al.
adolescence and young adulthood are associated with psychiatric
morbidity and future adult mortality, and the outcome tends to be
worse with more severe and repeated injury (Sariaslan et al., 2016).
Some studies have evidenced that TBI in late adolescence and
adulthood is related to an elevated risk of suicide (Fazel et al., 2014;
Richard et al., 2015). One study of the veterans of the U.S. War in Af-
ghanistan and the Iraq War revealed that veterans who sustained TBI
were 3.7 times more likely to attempt suicide than those who had not.
The tendency toward attempted suicide was more significantly medi-
ated when TBI was comorbid with psychiatric conditions (Fonda et al.,
2017). A large Swedish population study demonstrated a 3.3-fold in-
creased risk of mortality resulting from suicide after TBI, relative to the
general population (Fazel et al., 2014). Omalu et al. published a
shocking report regarding the association between chronic traumatic
encephalopathy and suicidality among American football players
(Omalu et al., 2011). Studies have suggested that the disproportionate
number of completed suicides in football players are multifactorial and
that causes include alcohol and substance abuse, retirement from
sports, psychiatric conditions, and especially, multiple TBI events
(Webner and Iverson, 2016; Wortzel et al., 2013).
Adolescents and young adults are vulnerable to TBI and suicide
(Annor et al., 2018; Tagliaferri et al., 2006). Both TBI and suicide lead
to unpleasant consequences for victims, families, and society; TBI and
suicide are especially unpleasant when the victims are young. To our
knowledge, no peer-reviewed journal has published a large cohort
study to evaluate the risk of attempted suicide for adolescents and
young adults who have experienced TBI. Therefore, our study also in-
vestigated the influences of injury severity, repetitive injury, and co-
morbid psychiatric conditions on attempted suicide among adolescents
and young adults.
2. Methods
2.1. Data source
In 1995, Taiwan implemented the National Health Insurance pro-
gram, a compulsory and universal health insurance program offering
comprehensive medical care coverage to all residents of Taiwan. The
National Health Research Institutes (NHRI) administers the National
Health Insurance Research Database (NHIRD), a database of insurance
claims consisting of healthcare data from >99% of the population of
Taiwan. The NHRI audits the NHIRD and releases data for academic
research. To protect patient privacy, when individual medical records
are extracted from the NHIRD, the information is deidentified, and
patient anonymity is guaranteed. The database contains comprehensive
data on insured individuals, including their demographic character-
istics, clinical visit dates, disease diagnoses, and medical interventions.
The codes of the International Classification of Diseases, Ninth
Revision, Clinical Modification (ICD-9-CM) are used for disease diag-
nosis. Numerous Taiwanese epidemiological studies have used the
NHIRD (Chen et al., 2016, 2015; Li et al., 2012; Wang et al., 2014). The
present study was initiated after approval from the Institutional Review
Board of Taipei Veterans General Hospital.
2.2. Inclusion criteria for TBI and control cohorts
The TBI cohort included adolescents (aged 12–17 years) and young
adults (aged 18–29 years) with no history of suicide attempts before
enrollment, who had received diagnoses of TBI from board-certificated
surgeons, internal medicine physicians, pediatricians, or emergency
medicine physicians on the basis of either their clinical judgment or
brain imaging assessment between January 1, 1998, and December 31,
2008. The time of TBI diagnosis was deemed the time of enrollment. An
age-matched, sex-matched, and enrollment time–matched (1:4) control
cohort was randomly formed after excluding the study individuals, in-
dividuals who had received a diagnosis of TBI, and individuals with a
22
Journal of Affective Disorders 250 (2019) 21–25
history of suicide attempts prior to enrollment. Any suicide attempt was
identified during follow-up (from enrollment to December 31, 2011, or
until death) and was defined by the codes for suicide attempts and
nonaccidental poisonings by drugs and nonmedical substances.
Psychiatric comorbidities, including unipolar depression, bipolar dis-
order, anxiety disorders, alcohol use disorders, and substance use dis-
orders, were assessed as the confounding factors in our study. We also
assessed the level of urbanization (level 1 (most urbanized) to level 5
(least urbanized)) as a variable in this study (Liu et al., 2006).
2.3. Statistical analysis
The continuous and nominal variables in the two groups were
compared using the F test and Pearson's X2 test, respectively, as ap-
propriate. Cox regression analyses were performed after adjustment for
demographic data (age, sex, income, and urbanization level) and psy-
chiatric comorbidities to calculate hazard ratios (HRs) with a 95%
confidence interval (CI) for any suicide attempt in the TBI and control
cohorts. Moreover, subanalyses stratified by TBI age (12–17 years or
18–29 years) and instances (1 time, ≥2 times) of TBI were performed to
investigate any age effects of TBI as well as the effects of repeated TBI
on the risk of attempting suicide. In addition, we assessed the severity
of TBI with the subsequent risk of attempted suicide. TBI severity was
defined as follows—severe: receiving neurosurgical operation for TBI
(craniotomy and craniectomy); moderate: being admitted due to TBI
after brain imaging assessment; mild: neither receiving operation nor
being admitted due to TBI. Two-tailed P < 0.05 was considered statis-
tically significant. All data processing and statistical analyses were
performed using Statistical Package for Social Science (SPSS) version 17
software (SPSS Inc.) and Statistical Analysis Software (SAS) version 9.1
(SAS Institute, Cary, NC).
3. Results
Demographic data and the incidence of attempted suicide are listed
in Table 1. The TBI cohort comprised 31,599 adolescents and young
adults who had sustained TBI. The control group consisted of 126,396
controls without TBI events in a 1:4 ratio. The age and sex at enrollment
were matched, with the average age being 21.09 ± 4.58–4.59 years.
The overall incidence of attempted suicide was significantly higher in
the TBI cohort than in the control cohort (4.6% versus 1.0%,
P < 0.001). The age at first suicide attempt in the TBI cohort was sig-
nificantly younger than that in the controls (mean 25.71 versus 28.99
years, P < 0.001). Therefore, the time interval between enrollment and
suicide attempt was shorter in the TBI cohort (P < 0.001). Psychiatric
comorbidities, urbanization of their residential region, and their in-
come-related insured amount were remarkably different between the
TBI and control groups. Significantly more psychiatric comorbidities,
namely anxiety, unipolar depression, bipolar, and alcohol and sub-
stance abuse, were related to the TBI cohort (all P < 0.001). Patients
with TBI were more likely to reside in underdeveloped areas. Their
income-related insured amount was lower than those of the control
group, indicating an inferior economic status in the TBI cohort.
To further evaluate the independent effect of TBI on attempted
suicide, demographic data (age, sex, income, and level of urbanization)
and psychiatric comorbidities (anxiety, unipolar depression, bipolar,
and alcohol and substance abuse) were adjusted using a Cox regression
model to analyze the HRs (Tables 2–4). A dose–response relationship
with TBI severity can be seen in Table 2. The risk of attempted suicide
was most elevated among subjects with severe TBI (adjusted HR 6.75
and 5.38, 95% CI, 5.03–9.07 and 4.00–7.23, respectively). After ad-
justing for the confounding factors, unipolar depression, bipolar dis-
order, and alcohol and substance use disorder were identified as in-
dependent risk factors for attempted suicide in the TBI cohort (adjusted
HR 2.83, 2.43, 2.57, and 1.88; 95% CI 2.52–3.18, 1.97–2.99, 2.25–2.94,
and 1.65–2.15, respectively).
H.-K. Chang, et al. Journal of Affective Disorders 250 (2019) 21–25

Table 1 Table 3
Demographic data and incidence of any suicide attempt among adolescents and Cox regression analysis of the risk of any suicide attempt among adoles-
young adults with TBI and controls. cents and young adults with TBI and controls, stratified by age and sex.
a
Adolescents and Controls p-value Suicide attempt
young adults (n = 126,396) HR (95% CI)
with TBI
(n = 31,599) TBI age
Adolescents (12–17 years) 4.37 (3.74–5.11)
Age at enrollment (years, SD) 21.09 (4.58) 21.09 (4.59) 0.952 Young adults (18–29 years) 3.71 (3.40–4.06)
Sex (n, %) 1.000 Sex
Male 17,113 (54.2) 68,452 (54.2) Males 3.71 (3.31–4.15)
Female 14,486 (45.8) 57,944 (45.8) Females 4.01 (3.60–4.46)
Severity of TBI (n, %)
Mild 22,774 (72.1) TBI: traumatic brain injury; HR: Hazard ratio; CI: Confidence interval.
Moderate 8185 (25.9) Bold type means the statistical significance.
Severe 640 (2.0) a
adjusting for demographic data and psychiatric comorbidities.
Incidence of any suicide attempt 1469 (4.6) 1269 (1.0) <0.001
(n, %)
Age at first suicide attempt 25.71 (5.25) 28.99 (5.26) <0.001 Table 4
(years, SD) Cox regression analysis of the risk of any suicide attempt among
Duration between 4.47 (3.15) 6.92 (2.97) <0.001 adolescents and young adults with TBI and controls, stratified by
enrollment and the first numbers of TBI.
suicide attempt (years, SD)
a
Psychiatric comorbidities (n, %) Suicide attempt
Anxiety disorders 216 (0.7) 580 (0.5) <0.001 HR (95% CI)
Unipolar depression 1965 (6.2) 3553 (2.8) <0.001
Bipolar disorder 326 (1.0) 450 (0.4) <0.001 Numbers of TBI
Alcohol use disorders 1316 (4.2) 1565 (1.2) <0.001 Non-TBI controls 1
Substance use disorders 1553 (4.9) 2673 (2.1) <0.001 1 3.43 (3.13–3.77)
Level of urbanization <0.001 ≥2 (repeated TBIs) 4.43 (4.04–4.87)
1 (most urbanized) 9025 (28.6) 41,731 (33.0)
2 10,098 (32.0) 39,623 (31.3) TBI: traumatic brain injury; HR: Hazard ratio; CI: Confidence in-
3 6004 (19.0) 23,522 (18.6) terval.
4 4140 (13.1) 14,558 (11.5) Bold type means the statistical significance.
5 (most rural) 2332 (7.4) 6962 (5.5) a
adjusting for demographic data and psychiatric comorbidities.
Income-related insured amount <0.001
≤ 15,840 NTD/month 10,637 (33.7) 39,128 (31.0)
15,841–25,000NTD/month 12,545 (39.7) 47,170 (37.3)
4. Discussion
≥ 25,001NTD/month 8417 (26.6) 40,098 (31.7)
In the United States, TBI accounts for approximately 840,000 hospital
TBI: traumatic brain injury; NTD: new Taiwan dollar; SD: standard deviation. and emergency department visits annually in patients younger than 25
years (Sariaslan et al., 2016). Overall prevalence can reach as high as
Table 2
nearly 30% for individuals between 0 and 25 years of age. Although
Cox regression analyses of the risk of any suicide attempt among adolescents 70%–90% of the TBIs in the present study were classified as mild injury or
and young adults with TBI and controls. concussion, a typical TBI has long-lasting consequences. It is now well-
known that TBI is a major public health concern (McKinlay et al., 2008).
Model 1a Model 2b
HR (95% CI) HR (95% CI)
Our study demonstrated the incidence of attempted suicide markedly
increased following TBI events in adolescents and young adults. The age
TBI (presence vs absence) 4.59 (4.26–4.95) 3.86 (3.58–4.18) at first suicide attempt was significantly younger than that of the controls
Mild 4.49 (4.13–4.89) 3.89 (3.58–4.24) without TBI. After calculations had been adjusted for confounding factors,
Moderate 4.66 (4.18–5.20) 3.69 (3.30–4.13)
namely demographics and psychiatric comorbidities, the hazard ratio of
Severe 6.75 (5.03–9.07) 5.38 (4.00–7.23)
Psychiatric comorbidities (n,%) attempted suicide was still significantly elevated in the TBI cohort. The
Anxiety disorders 0.95 (0.69–1.30) co-existence of unipolar depression, bipolar disorder, alcohol, or sub-
Unipolar depression 2.83 (2.52–3.18) stance abuse independently increased the risk of attempted suicide fol-
Bipolar disorder 2.43 (1.97–2.99)
lowing TBI. Severe TBI, female sex, adolescent status, and repeated TBI
Alcohol use disorders 2.57 (2.25–2.94)
Substance use disorders 1.88 (1.65–2.15)
events were associated with higher risks of attempted suicide compared
respectively with milder TBI, male sex, young adult status, and a single
TBI: traumatic brain injury; HR: Hazard ratio; CI: Confidence interval. TBI event. In contrast to the control cohort, long-term cumulative in-
Bold type means the statistical significance. cidence of attempted suicide significantly increased in the TBI cohort. To
a
adjusting for demographic data. the best of our knowledge, this is the first investigation of the risk of
b
adjusting for demographic data and psychiatric comorbidities. attempted suicide following TBI in this age category that uses a large
database and numerous cases. The primary strength of our study was the
We further investigated the hazard of attempted suicide by strati- ability to obtain longitudinal records from a national health care system
fying the age of TBI occurrence, sex, and frequency of TBI events with nearly 99% of the population enrolled and a complete follow-up
(Tables 3–4). Higher rates of attempted suicide were observed in pa- database. Investigating suicidal behavior following TBI with a large pro-
tients who sustained TBI during adolescence (adjusted HR 4.37, 95% spective observational study is challenging. The long-term tracking in
CI, 3.74–5.11), were female (adjusted HR 4.01, 95% CI, 3.60–4.46), and such prospective study is almost impossible, and patients are easily lost to
experienced repeated TBI events (≧2 times, adjusted HR 4.43, 95% CI, follow-up. Furthermore, mortality rates for adolescents and young adults
4.04–4.87). An analysis of the long-term data for more than 10 years of are low in developed countries such as Taiwan. Accordingly, large sam-
follow-up proved that the cumulative hazards of any suicide attempt ples sizes and long follow-up periods are necessary to accumulate an
among adolescents and young adults were significantly elevated in the adequate number of cases to understand the trend and to ensure appro-
TBI cohort compared with the controls (P < 0.001, Fig. 1). priate statistical power in the analysis.

23
H.-K. Chang, et al.
Fig. 1. Cumulative hazards of developing any suicide attempt among adolescents and young adults with TBI and controls. (TBI: traumatic brain injury).
Fazel et al. investigated suicide and premature mortality for adults
following TBI by using a Swedish population cohort (Fazel et al., 2014).
Relative to the general population and unaffected siblings, 3- and 2.6-
fold increased odds of mortality were noted, respectively. The external
causes included suicide, injury, and assaults. They also reported high
premature mortality in the subset of their TBI cohort that was comorbid
with psychiatric disorders and substance abuse. Our study directly de-
monstrated an elevated incidence of attempted suicide after TBI in
adolescents and young adults and substantially elevated risk when co-
morbid with psychiatric disorders and substance abuse.
We also examined whether TBI alone tended to independently as-
sociate with the increase of attempted suicide. Our data (Table 4) de-
monstrated that any single TBI event was associated with a 3.43-fold
increased risk of attempted suicide after adjusting for psychiatric condi-
tions and demographics. Repeated TBI events increased the risk 4.43-fold.
The underlying mechanism through which TBI independently increased
attempted suicide remains unclear. TBI has been linked to impulsivity and
self-destructive behaviors among veterans and adults (James et al., 2014;
Rochat et al., 2010). In children with severe TBI, raised intracranial
pressure caused long-term deficits in impulsivity, attention, and executive
function (Slawik et al., 2009). Similarly, an animal model demonstrated
that TBI can increase impulsivity in rats (Vonder Haar et al., 2017). Im-
pulsivity and aggression have been associated with suicide risk in aldo-
lescents (Gorlyn, 2005). Biological data suggested a behavior pathway of
suicide following TBI, mediated by tumor necrosis factor (TNF)-α to
disinhibition and impulsivity (Juengst et al., 2014). A study published
24
Journal of Affective Disorders 250 (2019) 21–25
direct radiographic evidence for suicidality after TBI; magnetic resonance
images from 15 male veterans with TBI proved that abnormal frontal
white matter tracts were associated with both impulsivity and suicidality
(Yurgelun-Todd et al., 2011). A growing body of evidence suggests a
connection between TBI and suicidality through impulsive behaviors and
poor inhibition performance. Nevertheless, the present study cannot
verify if there was a causal relationship between TBI and suicide attempt
based on the possibility of collider bias. It is likely that either TBI or
suicide attempts happened frequently in the experimental group, and a
false association may present if such group was controlled. Although the
incidence of suicide attempt following TBI among adolescents and young
adults in the present study (4.6%) was not increased relative to the
general population using data collected from the National Trauma Data
Bank (3.0–8.2%), the possibility of collider bias cannot be completely
eliminated (Kesinger et al., 2016).
One limitation of our study was our inability to review each in-
dividual's medical chart and radiographic image in detail. Therefore,
the severity of TBI could not be determined using conventional mea-
sures such as the Glasgow Coma Scale; thus, severity was determined
from interventions applied to patients. The management strategy fol-
lowed the treatment guidelines endorsed by major pediatric critical
care societies and neurosurgical associations in the United States
(Kochanek et al., 2012). Although a randomized prospective study in-
volving a TBI and a non-TBI cohort would be ideal to study our hy-
pothesis, it would be difficult to track the long-term incidence in the
observational period and to obtain complete follow-up records.
H.-K. Chang, et al.
5. Conclusion
Our data suggested that TBI was related to a substantially elevated
incidence of attempted suicide in adolescents and young adults. TBI
severity, repetitive injury, female sex, young age at injury, and certain
psychiatric comorbidities (unipolar depression, bipolar disorder, al-
cohol, and substance use disorders) were associated with an elevated
risk of attempted suicide. Cumulative hazards (>10 years) of any sui-
cide attempt among adolescents and young adults were significantly
elevated in the TBI cohort relative to the control cohort.
Conflict of interest
No competing financial interests exist.
Funding
The study was supported by grant from Taipei Veterans General
Hospital (V103E10-001, V104E10-002, V105E10-001-MY2-1, V105A-
049, V106B-020, V107B-010, V107C-181). The funding source had no
role in any process of our study.
Financial disclosure
All authors have no financial relationships relevant to this article to
disclose.
Declaration of interest
None.
Acknowledgment
We thank Mr I-Fan Hu for his friendship and support.
Authors’ contribution
Hsuan-Kan Chang, Ju-Wei Hsu, Jau-Ching Wu, Kai-Lin Huang,
Huang-Chou Chang, Ya-Mei Bai, Tzeng-Ji Chen, Mu-Hong Chen
HKC, JWH, JCW, HCC, MHC: conception and design, and/or ac-
quisition of data, and/or analysis and interpretation of data; HKC, JCW,
KLH, MHC: drafting the article or revising it critically for important
intellectual content; YMB, TJC, MHC: Collect data, Performed bioin-
formatics and statistical analyses; HCC, YMB, TJC: Supervised the re-
search; All authors have critically revised and approved the final article.
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