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IMPORTANCE Suicide attempts are strong predictors of suicide, a leading cause of adolescent jamapsychiatry.com
mortality. Suicide attempts are highly familial, although the mechanisms of familial
transmission are not understood. Better delineation of these mechanisms could help frame
potential targets for prevention.
DESIGN, SETTING, AND PARTICIPANTS In this prospective study conducted from July 15, 1997,
through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of
334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a
suicide attempt, were followed up for a mean of 5.6 years.
MAIN OUTCOMES AND MEASURES The primary outcome was a suicide attempt. Variables were
examined at baseline, intermediate time points, and the time point proximal to the attempt.
Participants were assessed by structured psychiatric assessments and self-report and by
interview measures of domains hypothesized to be related to familial transmission (eg, mood
disorder and impulsive aggression).
RESULTS Among the 701 offspring, 44 (6.3%) had made a suicide attempt before
participating in the study, and 29 (4.1%) made an attempt during study follow-up.
Multivariate logistic regression revealed that proband suicide attempt was a predictor of
offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75-13.07), even controlling for
other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI,
1.37-12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94-16.74), and mood
disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29-56.00). Path analyses
were consistent with these findings, revealing a direct effect of proband attempt on offspring
suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive
aggression as a precursor of mood disorder. Author Affiliations: Department of
Psychiatry, University of Pittsburgh
School of Medicine, Pittsburgh,
CONCLUSIONS AND RELEVANCE Parental history of a suicide attempt conveys a nearly 5-fold
Pennsylvania (Brent, Melhem,
increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting Birmaher, Biernesser, Kolko, Zelazny,
for the familial transmission of mood disorder. Interventions that target mood disorder and Iyengar); Western Psychiatric
impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal Institute and Clinic, University of
Pittsburgh Medical Center,
behavior.
Pittsburgh, Pennsylvania (Brent,
Birmaher, Biernesser, Kolko, Porta,
Zelazny); Division of Molecular
Imaging and Neuropathology,
Department of Psychiatry, Columbia
University and New York State
Psychiatric Institute, New York
(Oquendo, Burke, Stanley, Keilp,
Ellis, Mann).
Corresponding Author: David A.
Brent, MD, Western Psychiatric
Institute and Clinic, University of
Pittsburgh Medical Center, 3811
OHara St, Bellefield Towers, Room
JAMA Psychiatry. 2015;72(2):160-168. doi:10.1001/jamapsychiatry.2014.2141 311, Pittsburgh, PA 15213 (brentda
Published online December 30, 2014. @upmc.edu).
A
ccording to a review article,1 adoption, twin, and fam- Site Differences
ily studies have established that suicidal behavior is fa- At baseline, after FDR correction, offspring in Pittsburgh, com-
milial. Moreover, the phenotype that is transmitted is pared with offspring in New York, were younger (mean [SD],
a suicide attempt or suicide rather than suicidal ideation.2,3 15.4 [6.8] vs 19.1 [10] years; t210.7 = 4.09; P < .001; q < .001), less
However, few studies4-6 have addressed the pathways by which likely to be Hispanic (1.6% vs 25.6%; 21 = 101.97; P < .001;
suicidal behavior is transmitted in families. q < .001), and followed up for a longer period of time (mean
To address this gap in the literature, we began the Famil- [SD], 6.1 [3.7] vs 4.9 [3.8] years; t699 = 4.06; P < .001).
ial Pathways to Early-Onset Suicidal Behavior study, in which
we followed up the offspring of parents with a mood disor- Assessment
der, with approximately half the parents in the study having Probands and offspring were assessed by separate, masked
a history of a suicide attempt. Previous studies7-11 have indi- clinical interviewers (C.B.). Baseline interviews covered life-
cated that offspring of suicide attempters had a 4- to 6-fold time occurrence of suicidal ideation and behavior, aggres-
greater risk of a suicide attempt and that possible mediators sion, and psychiatric disorders. Subsequent annual inter-
of familial transmission included the intrafamilial transmis- views covered these domains since the last assessment. These
sion of impulsive aggression, mood disorder, and childhood interviews, along with self-report questionnaires, targeted
maltreatment. However, these reports were cross-sectional or known contributors to suicidal risk, namely, previous at-
covered 1 to 2 years of follow-up with relatively few suicide at- tempt and suicidal ideation; mood, anxiety, and behavioral dis-
tempts among offspring. orders; impulsive aggression; Cluster B personality disorders
In contrast, we report on offspring of parents with mood (ie, borderline, antisocial, or narcissistic); family discord; his-
disorders who were followed up for a mean of 5.6 years. Con- tory of head trauma; and history of abuse.12-14 eTable 1 in the
sequently, a much larger proportion of this cohort is past the Supplement lists all assessments, targeted domains, and pe-
peak age at onset of mood disorder and suicidal behavior. On riods covered.
the basis of previous work and the extant literature, we hy- Suicidal behavior was assessed using the Columbia His-
pothesized that proband suicide attempt would predict off- tory of Suicide Form and classified as suicidal ideation, sui-
spring suicide attempt, even after controlling for the familial cide attempt, interrupted attempt, or aborted attempt as per
transmission of mood disorders, and that the familial trans- t h e C o l u m b i a C l a s s i f i c at i o n A l go r it h m fo r S u i c i d e
mission of suicidal behavior would be mediated by the famil- Attempts.15,16 Interrater reliability with the Columbia History
ial transmission of mood disorder, impulsive-aggressive traits, of Suicide Form is high ( = 0.97), as was the convergent
and childhood physical or sexual abuse. validity with the Columbia Suicide Severity Rating Scale.17,18
A suicide attempt was defined as a self-destructive act that
resulted in potential or actual tissue damage with inferred or
explicit intent to die.15 Suicide-related behavior included
Methods interrupted and aborted attempts and emergency referrals
Sample for suicidal ideation but not suicide attempts. Suicidal ide-
This study was reviewed and approved by the University of ation was assessed by the Scale for Suicidal Ideation19 or the
Pittsburgh Institutional Review Board and the New York State downward extension for youth younger than 14 years. 20
Psychiatric Institute Institutional Review Board, and written Nonsuicidal self-injury (NSSI) was assessed consistent with
informed consent or assent was obtained from all partici- its definition in the Columbia Classification Algorithm for
pants. The sample consisted of 701 offspring of 334 probands Suicide Attempts.15
with mood disorders, with 191 (57.2%) of the probands hav- Aggression was measured using the Brown-Goodwin Life-
ing made a suicide attempt and a mean (SD) number of off- time History of Aggression in all participants.21 Axis I disor-
spring siblings per proband of 2.1 (1.0) (Table 1). Most pro- ders were assessed by the Structured Clinical Interview for
bands were clinically referred to the Western Psychiatric DSM-IV for participants 18 years and older22 and by the Sched-
Institute or the New York State Psychiatric Institute, the 2 sites ule for Affective Disorders and Schizophrenia for School-Age
of this study, from July 15, 1997, through September 6, 2005, Children, Present and Lifetime Version, in youth.23 The Struc-
and followed through June 21, 2012. tured Clinical Interview for DSM-IV was augmented with a
module for the assessment of attention-deficit/hyperactivity
Follow-up disorder derived from the Schedule for Affective Disorders and
Offspring were followed up for a mean (SD) of 5.6 (3.8) years, Schizophrenia for School-Age Children, Present and Lifetime
with retention rates of 88.6%, 81.7%, 60.1%, 61.1%, and Version. Interrater reliability on depressive diagnoses for spe-
58.6% of the sample from intake for years 1 through 5, cific ( = 0.96; 95% CI, 0.90-1.00) and the full range of diag-
respectively; probands were also followed up prospectively. noses ( = 0.65-0.96) was high. Personality disorders in pro-
No baseline differences were found between those who were bands and offspring 18 years or older were assessed using the
retained and those who were lost to follow-up after correc- Structured Clinical Interview for DSM-IV Axis II disorders.24
tion for the false discovery rate (FDR) and there was no dif- Socioeconomic status of the head of household was assessed
ference in the rate of follow-up of offspring of suicide using Hollingsheads Four Factor Index of Social Status.25
attempters vs nonattempters (hazard ratio, 1.10; 95% CI, Race and ethnicity were based on the respondents self-
0.66-1.82; z = 0.35; P = .73). assessment.
jamapsychiatry.com (Reprinted) JAMA Psychiatry February 2015 Volume 72, Number 2 161
Table 1. Demographic and Clinical Characteristics of Offspring and Probands at Baseline Assessmenta
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; MDD, major were found except for offspring race, proband Cluster B personality disorder,
depressive disorder; NA, not applicable; OCD, obsessive-compulsive disorder; and proband lifetime alcohol or substance abuse (P < .001, q < .001).
PTSD, posttraumatic stress disorder. b
On the basis of participants self-report.
a
Data are presented as number (percentage) of study participants unless c
Only assessed in those 18 years or older.
otherwise indicated. No statistically significant differences between groups
162 JAMA Psychiatry February 2015 Volume 72, Number 2 (Reprinted) jamapsychiatry.com
ers. All 3 of these time points were before the assessed out-
Figure 1. Risk of Offspring Suicide Attempt by Proband History of
come (actual suicide attempt), thus maintaining the temporal Attempts
sequence for predictive models. Self-reports of symptom se-
verity were not included with other baseline variables to re- 0.30
Proband suicide attempter
duce the number of variables examined. Dichotomous vari-
ables, such as diagnosis, were counted as present if they
Proportion of Offspring
occurred during at least one of the intermediate time points, 0.20
and the most severe rating of suicidal ideation was reported,
whereas self-report data were averaged across intermediate
time points. We also examined proband lifetime diagnoses up 0.10
to the time point of offsprings suicide attempt or maximum Proband nonattempter
time point. We controlled a priori for proband lifetime sui-
cide attempts in all models. 0
Variables that were significant after using the FDR with the 0 20 40 60
Yekutieli and Benjamini43 method to account for correlations Age, y
among variables (qqvalue package in STATA statistical soft-
ware, version 11.2, Stata Corp) were included in multivariate Wilcoxon test: 12 = 7.01, P = .008; log-rank test: 12 = 8.19, P = .004.
jamapsychiatry.com (Reprinted) JAMA Psychiatry February 2015 Volume 72, Number 2 163
Table 2. Demographic and Clinical Characteristics of Offspring and Proband and Risk of Suicide Attempt in Offspring
Time Points
Baseline Intermediate Proximala
Characteristic OR (95% CI) P Value OR (95% CI) P Value OR (95% CI) P Value
Offspring
Age 0.99 (0.96-1.02) .37 NA NA NA
Sex 1.56 (0.74-3.27) .24 NA NA NA
White 0.77 (0.34-1.72) .52 NA NA NA
Hispanic 1.46 (0.51-4.16) .48 NA NA NA
Site 0.90 (0.42-1.92) .79 NA NA NA
Mood disorder 8.68 (3.41-22.11) <.001b 5.88 (2.55-13.57) <.001b 16.77 (3.59-78.33) <.001b
ADHD 2.76 (0.99-7.64) .05 2.90 (1.28-6.57) .01 7.03 (1.65-29.91) .008
PTSD 3.36 (1.34-8.45) .01 3.81 (1.45-10.03) .007 6.87 (1.73-27.27) .006
Anxiety disorder 1.51 (0.69-3.26) .30 3.36 (1.63-6.93) .001c 1.61 (0.41-6.27) .49
Eating disorder 4.94 (1.33-18.37) .02 NA NA NA NA
Alcohol or substance 2.40 (1.04-5.52) .04 2.59 (1.18-5.71) .02 0.47 (0.06-3.77) .48
abuse
Behavioral or antisocial 2.91 (1.26-6.71) .01 3.19 (1.38-7.35) .007 5.28 (1.36-20.44) .02
disorder
Depression, self-report NA NA 1.89 (1.43-2.51) <.001b 1.72 (1.12-2.63) .01
Hopelessness NA NA 1.45 (1.07-1.98) .02 1.68 (1.10-2.58) .02
Impulsivity 1.95 (1.31-2.90) .001c 2.61 (1.77-3.84) <.001b 1.82 (0.94-3.50) .07
Impulsive aggression 2.16 (1.35-3.44) .001c 2.40 (1.47-3.91) <.001b 2.65 (0.97-7.24) .06
b
Aggression 2.01 (1.43-2.83) <.001 1.45 (1.03-2.04) .04 1.81 (1.38-2.37) <.001b
Negative life events NA NA 2.00 (1.51-2.65) <.001b 2.61 (1.50-4.52) .001c
Reasons for living NA NA 0.92 (0.54-1.56) .76 0.56 (0.24-1.29) .17
Social support NA NA 0.74 (0.50-1.11) .15 0.73 (0.36-1.50) .39
Family adaptability or NA NA 0.93 (0.87-0.99) .02 0.96 (0.90-1.2) .20
cohesion
Nonsuicidal self- 6.98 (2.41-20.24) <.001b 7.67 (2.02-29.15) .003c 11.02 (3.03-40.11) <.001b
injurious behavior
Lifetime history of 2.12 (0.97-4.62) .06 NA NA NA NA
physical or sexual abuse
History of suicide 11.03 (4.87-24.99) <.001b NA NA NA NA
attemptd
History of suicide- 3.64 (0.88-15.04) .07 NA NA NA NA
related behaviorsd
Suicidal ideation 1.18 (1.05-1.33) .007 1.27 (1.16-1.39) <.001b 0.98 (0.76-1.26) .87
Suicide-related NA NA 5.88 (2.09-16.56) .001c 7.96 (0.80-79.46) .08
behaviors
Proband
Mood 1.05 (0.31-3.56) .94 1.41 (0.49-4.04) .52 1.68 (0.69-4.10) .25
Alcohol or substance 1.88 (0.86-4.14) .12 1.25 (0.54-2.89) .60 0.38 (0.09-1.66) .20
abuse
PTSD 1.33 (0.57-3.16) .51 1.49 (0.70-3.20) .30 2.17 (0.91-5.16) .08
Anxiety 1.26 (0.59-2.85) .58 0.74 (0.36-1.51) .40 0.76 (0.35-1.67) .50
Cluster B personality 2.19 (0.98-4.91) .06 NA NA NA NA
disorder
Lifetime history of 0.83 (0.29-2.39) .73 NA NA NA NA
physical or sexual abuse
Lifetime history of 4.49 (1.56-12.90) .005 NA NA NA NA
suicide
Impulsivity 1.02 (0.99-1.04) .18 1.01 (.99-1.03) .44 1.01 (0.97-1.05) .70
Impulsive aggression 1.02 (0.99-1.06) .24 1.02 (0.98-1.07) .29 1.05 (0.97-1.14) .26
Aggression 1.26 (0.92-1.74) .15 1.11 (0.73-1.70) .62 1.06 (0.78-1.44) .71
b
Abbreviations: ADHD, attention-deficit/hyperactivity disorder; NA, not q < .001.
applicable; OR, odds ratio; PTSD, posttraumatic stress disorder. c
q < .05.
a
Time point immediately before the onset of an actual suicide attempt or d
Compared with no event.
maximum time point for suicide nonattempters.
164 JAMA Psychiatry February 2015 Volume 72, Number 2 (Reprinted) jamapsychiatry.com
Figure 2. Path Analysis Including Predictors of Suicide Attempt and Mood Disorder at the Prior Time Point
History of Mood
Suicide Attempt Disorder
0.74 b 0.27 b
Black line indicates baseline variables;
1a
0.3
0.3
0.52
b paths are statistically significant. The
0
c
site, and proband suicide attempt. Using backward stepwise Path Model
regression, the most parsimonious set of variables associated Path analyses were conducted that included predictors of off-
with offspring suicide attempt were offspring mood disorder spring mood disorder at a proximal time point (eTable 1 in the
at baseline, a history of an offspring suicide attempt before en- Supplement) and predictors of offspring suicide attempt
try into the study, offspring mood disorder at the time point (Table 3 and Figure 2). We report the path coefficients and sta-
before the suicide attempt, and proband suicide attempt. There tistical significance for the entire path being described. Pro-
were no main effects of offspring age, offspring or proband sex, band suicide attempt had a direct effect on offspring attempt
or offspring or proband polarity of mood disorder on off- ( = 0.52, SE = 0.20, z = 2.64, P = .008). However, the indirect
spring suicide attempt and no significant interactions of any pathway from proband attempt via proband Cluster B, off-
variables with proband attempt (Table 3). spring impulsive aggression, and mood disorder before the at-
tempt was not statistically significant ( = 0.03, SE = 0.02,
Predictors of Mood Disorder at the Proximal Time Point P = .08). Offspring history of a previous suicide attempt had a
Because offspring mood disorder at the proximal time point direct path to offspring suicide attempt ( = 0.74, SE = 0.26,
to the attempt was among the strongest predictors of a sui- z = 2.87, P = .004). The effects of previous attempts and pre-
cide attempt, we tried to deconstruct this variable by identi- vious suicide-related behavior in offspring were also medi-
fying those baseline and intermediate variables most closely ated via offspring impulsive aggression and mood disorder
associated with it (eTable 2 in the Supplement), which were ( = 0.05, SE = 0.02, z = 2.20, P = .03, and = 0.05, SE = 0.03,
baseline proband Cluster B disorder and offspring age, as well z = 1.95, P = .05, respectively). A final pathway was a consis-
as the following offspring variables assessed at intermediate tent effect of offspring mood disorder at baseline and each fol-
time points: mood disorder, anxiety disorder, eating disor- low-up point on offspring suicide attempt ( = 0.30, SE = 0.10,
der, and impulsive aggression. z = 2.86, P = .004).
jamapsychiatry.com (Reprinted) JAMA Psychiatry February 2015 Volume 72, Number 2 165
166 JAMA Psychiatry February 2015 Volume 72, Number 2 (Reprinted) jamapsychiatry.com
ARTICLE INFORMATION interpretation of the data; preparation, review, or 13. Mann JJ, Waternaux C, Haas GL, Malone KM.
Submitted for Publication: April 29, 2014; final approval of the manuscript; and the decision to Toward a clinical model of suicidal behavior in
revision received June 27, 2014; accepted August 4, submit the manuscript for publication. psychiatric patients. Am J Psychiatry. 1999;156(2):
2014. Additional Contributions: The following project 181-189.
Published Online: December 30, 2014. staff from the University of Pittsburgh provided 14. Fazel S, Wolf A, Pillas D, Lichtenstein P,
doi:10.1001/jamapsychiatry.2014.2141. outstanding work on this project: Joseph Park, MA, Lngstrm N. Suicide, fatal injuries, and other
who participated in manuscript preparation; causes of premature mortality in patients with
Author Contributions: Dr Brent has full access to Monica Walker Payne, MA, who provided traumatic brain injury: a 41-year Swedish population
all the data in the study and takes responsibility for leadership with project coordination; Thomas study. JAMA Psychiatry. 2014;71(3):326-333.
the integrity of the data and the accuracy of the Hahner, MS, and Emily Hogan, MSCP, LPC, NCC,
data analysis. 15. Posner K, Oquendo MA, Gould M, Stanley B,
who worked as clinical interviewers; Irina Davies M. Columbia Classification Algorithm of
Study concept and design: Brent, Melhem, Puchkareva, MS, who assisted with database
Oquendo, Birmaher, Keilp, Stanley, Mann. Suicide Assessment (C-CASA): classification of
management; and Dana Kaufman, BFA, who suicidal events in the FDAs pediatric suicidal risk
Acquisition, analysis, or interpretation of data: assisted with database entry.
Brent, Melhem, Oquendo, Burke, Birmaher, Stanley, analysis of antidepressants. Am J Psychiatry. 2007;
Biernesser, Kolko, Ellis, Porta, Zelazny, Iyengar, 164(7):1035-1043.
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