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Familial Pathways to Early-Onset Suicide Attempt
Risk for Suicidal Behavior in Offspring of Mood-Disordered Suicide Attempters
David A. Brent, MD;
Maria Oquendo, MD;
Boris Birmaher, MD;
Laurence Greenhill, MD;
David Kolko, PhD;
Barbara Stanley, PhD;
Jamie Zelazny, BSN;
Beth Brodsky, PhD;
Jeffrey Bridge, PhD;
Steve Ellis, PhD;
J. Octavio Salazar, MD;
J. John Mann, MD
Arch Gen Psychiatry. 2002;59:801-807.
ABSTRACT
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Background Although adoption, twin, and family studies have shown that suicidal
behavior is familial, the risk factors for familial transmission from parent
to child remain unclear.
Methods A high-risk family study was conducted comparing the offspring of 2
mood-disordered groups: suicide attempters and nonattempters. Recruited from
2 sites, probands were 81 attempters and 55 nonattempters, with 183 and 116
offspring, respectively. Offspring were assessed by investigators masked to
proband status. Probands and offspring were assessed with respect to psychopathologic
findings, suicide attempt history, impulsive aggression, and exposure to familial
environmental stressors.
Results Offspring of attempters had a 6-fold increased risk of suicide attempts
relative to offspring of nonattempters. Familial transmission of suicide attempt
was more likely if (1) probands had a history of sexual abuse and (2) offspring
were female and had a mood disorder, substance abuse disorder, increased impulsive
aggression, and a history of sexual abuse.
Conclusions The offspring of mood-disordered suicide attempters are at markedly
increased risk for suicide attempts themselves. Familial transmission of suicidal
behavior in families with mood disorders almost always requires transmission
of a mood disorder and is also related to the offspring's impulsive aggression
and the familial transmission of sexual abuse. Early treatment of mood disorders
and targeting impulsive aggression and sexual trauma may be helpful in the
prevention and treatment of suicidal behavior in families with mood disorders.
INTRODUCTION
SUICIDE ATTEMPTS are among the most serious complication of mood disorders.
Although most completed and attempted suicides occur in the context of a mood
disorder, most individuals with mood disorders never engage in suicidal behavior.1 Therefore, there must be factors other than the mood
disorder that predispose an individual to suicidal behavior. For example,
familial genetic or nongenetic factors increase the likelihood that a suicide
attempt will occur in the context of an episode of mood disorder.2-3
Adoption, family, and twin studies have demonstrated the familial transmission
of suicide and suicidal behavior. Biological, but not adoptive, relatives
of adoptees who commit suicide show a 6-fold higher risk for suicide compared
with the biological relatives of living control adoptees.4
A related adoption study showed a 15-fold greater risk of suicide in the biological
relatives of probands with mood disorders, with the highest rate in the relatives
of probands with affect reaction, a condition akin
to borderline personality disorder.5 Family
studies2-16
of probands who completed or attempted suicide report a 4- to 6-fold greater
risk of suicide or suicidal behavior in their relatives compared with the
relatives of community or patient controls. There is greater concordance for
monozygotic compared with dizygotic twins for completed and attempted suicide.17-19 In a large, representative
sample of Australian twins, the heritability of serious suicide attempts was
55%.19
The familial transmission of suicidal behavior may involve a common
liability for both completed and attempted suicide insofar as the rates of
attempted suicide are elevated in the relatives of completers2, 6-7,18
and the rates of completed suicide are elevated in the relatives of attempters.11, 13, 16, 20 Familial
transmission of suicidal behavior is not explained by transmission of mental
disorders alone, since increased risk for suicide or suicidal behavior persists
even after controlling for familial transmission of mental disorder.2, 6-7,10, 12, 19
Little is known about the factors responsible for familial transmission
of suicidal behavior. Familial transmission of mood disorders is thought to
be important but not sufficient for familial transmission of suicidal behavior.8 Impulsive aggression and violent suicidal behavior
in suicide attempters or completers are associated with much greater family
loading for suicidal behavior.6 Aggressive
traits and mood disorders may be familially transmitted by genetic or nongenetic
factors. Likewise, familial factors predisposing an individual to suicidal
behavior can be environmental or genetic.11-13
Family discord increases the risk for suicide attempt and completion in young
people.2-3,21 Maltreatment,
particularly sexual abuse, conveys a markedly increased risk for suicide and
suicidal behavior.22-26
Family discord and abuse may also be explained by increased rates of parental
mental disorder, tendency to impulsive aggression, and suicide attempt in
abusive parents.15, 27-28
Nevertheless, even after controlling for other family problems, sexual abuse
accounts for almost 20% of the population-attributable risk for suicide attempt
in young people.23-24 Imitation
is not a major mechanism in familial transmission, given the results of adoption
and twin studies and prospective studies of exposure to suicide.4-5,19, 29-30
Few studies have examined the risk factors for familial transmission,
which can provide insight into the causes of suicidal behavior and offer potential
targets for intervention. We describe a high-risk prospective family study
to examine the rate of and risk factors for suicidal behavior in the offspring
of 2 groups of parents with mood disorders: those with and those without a
history of suicide attempt. We tested 2 main hypotheses: (1) the offspring
of attempters, compared with the offspring of nonattempters, will show a higher
rate of suicide attempt, greater levels of impulsivity and aggression, and
greater exposure to family environmental stressors; and (2) the familial transmission
of suicide attempt will be explained by proband and offspring impulsivity
and aggression and family environmental stressors, not just by the transmission
of mood disorder.
SUBJECTS AND METHODS
SAMPLE AND RECRUITMENT METHODS
Two proband groups were recruited from inpatient units, namely, depressed
suicide attempters and a comparison group of depressed nonattempters, and
their biological offspring. All probands were classified as attempters or
nonattempters based on their report of a suicide attempt defined as "self-injurious
behavior with intent to die." Attempters were required to have made an attempt
with a Medical Damage Lethality Scale rating of at least 2, indicating physical
threat or sequelae that required medical evaluation or treatment.31 A proportion (43%) of the probands were recruited
from a pool of previous participants in biological studies of suicidal behavior,
last assessed 4 to 8 years previously, with a recruitment rate of 23%. Despite
the low participation rate, participants and nonparticipants were similar
with regard to Axis I and II diagnoses, impulsive aggression, and indices
of severity of suicidal behavior. Participants were more likely to be female
(P = .008) and married (P
= .03).
The remainder of the samples (n = 77, 57%) in Pittsburgh, Pa, and New
York, NY, was recruited from inpatient units following the same inclusion
and exclusion criteria as the original cohort, with an acceptance rate of
75%. Probands provided contact information for offspring and biological coparents
of offspring. In total, 299 offspring were recruited, with an acceptance rate
of 88%. For the 146 biological coparents, information was provided by direct
interview for 47% and by the proband for 29%, and no information was available
for 36%. Similar proportions of coparents of attempter and nonattempter probands
were directly interviewed (36% vs 50%). Informed consent for all interviews
was obtained as approved by the institutional review boards of the University
of Pittsburgh, Pittsburgh, St Francis Medical Center, Pittsburgh, and the
New York State Psychiatric Institute in New York City.
ASSESSMENT
Axis I Disorder
All subjects older than 18 years were assessed for the presence of lifetime
and current DSM-IV32
psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID-I).33 Biological coparents
not directly interviewed were assessed with regard to diagnosis and history
of suicidal and assaultive behavior using the Family History Research Diagnostic
Criteria34 (with criteria modified to DSM-IV) reported by either the proband or a biological
relative. Offspring between the ages of 10 and 17 years were assessed with
regard to Axis I disorders using the School Aged Schedule for Affective Disorders
and Schizophrenia, Present and Lifetime Version (K-SADS-PL).35
For offspring aged 2 to 9 years (n = 67, 22%), subjects were assessed solely
with the parent-report questionnaire, the Child Behavior Checklist (CBCL).36 History of suicidal behavior was assessed using the
Columbia University Suicide History Form, the Medical Damage Lethality Rating
Scale, and the Beck Suicide Intent Scale for the current and most severe attempts
in probands and all offspring 10 years and older.31, 37
Personality disorders were diagnosed using the Structured Clinical Interview
for the DSM-IV Diagnosis of Personality Disorders
(SCID-II) in all subjects older than 14 years.38
Aggression was rated using the 11-item Brown-Goodwin Lifetime History of Aggression
(BGLHA) in all subjects.39 Tendency to impulsive
aggression was assessed by the Buss-Durkee Hostility Inventory (BDHI) in all
subjects older than 14 years.40 In children
aged 10 to 13 years, the downward extension of the BDHI, the Children's Hostility
Inventory (CHI), was used.41 In subjects older
than 18 years, impulsivity was assessed using the Barratt Impulsivity Scale
(BIS).42 In subjects aged 10 to 17 years, the
5-item impulsivity subscale of the Iowa Conners Parent Physical Report was
used.43 In subjects older than 18 years, a
history of physical and sexual abuse was assessed from a series of screening
questions in our demographic questionnaire. As part of a 1-year follow-up,
a subset of subjects older than 18 years (n = 201) were reassessed with a
self-report measure of child trauma, the Child Experiences Questionnaire.44 Reliability with the initial assessment was moderate
for physical abuse ( = 0.41, SE = 0.11) and high for sexual abuse (
= 0.74, SE = 0.11). For children aged 10 to 17 years, a history of physical
and sexual abuse was assessed using the Psychosocial Schedule, an interview
with the parent and child about home and family environment.45
Patterns of maladaptive parenting were assessed using the child report of
the Conflict Tactics Scale (CTS).46 This scale
assesses the degree of 3 response patterns: reasoning, verbal aggression,
and physical violence following family conflicts. Family adaptability and
cohesion were assessed by the 20-item questionnaire Family Adaptability and
Cohesion Evaluation Scales (Version II), which were filled out by the child.47
Diagnostic Procedure
All interviewers were at least master's degree–level clinicians
or psychiatric nurses who received extensive training in the administration
of semistructured interviews. Assessments of offspring and probands were conducted
blind to each other. Best-estimate diagnoses were made by consensus and used
all available sources in diagnostic consensus conferences. Within-site and
cross-site reliability on the SCID-I and SCID-II, K-SADS-PL, suicide history,
and the BGLHA were high (intraclass correlation coefficient = 0.82-0.98,
= 0.86-0.95).
DATA ANALYSIS
Data for the 2 sites were combined after ascertaining that differences
between sites were not contributing to any risk factor–by–site
interactions with regard to familial transmission. The morbid risks of a suicide
attempt history in the offspring of attempters and nonattempters were compared
using the Kaplan-Meier estimate.48 Characteristics
of offspring who attempted and those who did not, as well as the characteristics
of their parents, were compared using the  2 test for dichotomous
variables and t tests for continuous variables. The
variables that discriminated between offspring of probands who did and did
not attempt suicide were entered into a mixed-effects nominal logistic regression
model along with site (Pittsburgh vs New York) and recruitment source (old
vs new sample).49 A mixed-effects model was
used to account for clustering of offspring within families, with covariates
included as fixed effects. Because the data had previously been examined for
a midpoint analysis,  was set at .025 for hypothesis-testing analyses.
As a further check, we conducted a separate set of analyses that treated the
family as the analytic unit.
RESULTS
PROBANDS
Table 1 gives the demographic
and clinical characteristics of the probands. Probands were middle-aged, mostly
female, and had mood disorders. Proband attempters made their first attempt
around the age of 30 years (mean ± SD, 31.5 ± 14.1 years). More
than half had made multiple attempts (56%), with high maximum intent (mean
± SD, 16.4 ± 5.6) and lethality (43.6 ± 1.8). Attempters
compared with nonattempters were more likely to be nonwhite and non-Catholic
and have diagnoses of posttraumatic stress disorder and cluster B disorder.
Probands recruited from Pittsburgh were younger (40.7 ± 9.7 vs 51.6
± 12.7 years, Mann-Whitney U test = 1092.0, P<.001), less likely to be college educated (49% vs
85%, 21 = 17.57, P<.001),
had higher rates of posttraumatic stress disorder (35% vs 15%, 21 = 6.15, P = .01), and had higher
rates of any alcohol or substance abuse (56% vs 31%, 21 = 8.19, P = .004) than the probands from
New York. However, these 4 variables conveyed similar risks for offspring
attempt in Pittsburgh and New York. Therefore, for subsequent analyses the
samples were combined. Coparents of attempters were younger (45.8 ±
10.6 vs 50.5 ± 12.5 years, t92
= 1.98, P = .05) and more likely to be nonwhite (34%
vs 12%, 21 = 5.64, P =
.02), but were otherwise similar.
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Table 1. Demographic and Clinical Characteristics of Probands*
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OFFSPRING
Offspring were on average in early adulthood, with age distribution
depicted in Table 2. Offspring
of attempters and nonattempters showed similar rates of Axis I and II disorders,
both lifetime (Table 2) and current
disorders.
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Table 2. Demographic and Clinical Characteristics of Offspring*
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There was a higher rate of suicide attempt in the offspring of attempters
than in the offspring of nonattempters (12% vs 2%, 21 = 6.96, P = .008). Per family analyses also
revealed a higher rate of offspring attempt in attempter vs nonattempter families
(20% vs 2.1%, Fisher exact test, P = .005). There
was also a higher morbid risk of attempt in offspring of attempters using
the Kaplan-Meier procedure (0.21 ± 0.05 vs 0.03 ± 0.02; Generalized
Savage 21 = 7.89; P =
.005; odds ratio [OR], 6.2; 97.5% confidence interval [CI], 1.2-33.4). Figure 1 shows that the peak age of incident
attempt was between 15 and 30 years, with a median age of onset of 16 years.
On 1-year follow-up, 5 of 39 nonattempter probands made a first suicide attempt.
When data were reanalyzed with these probands reclassified, the results were
essentially the same (OR, 5.4; 97.5% CI, 1.0-28.9).
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Cumulative proportion of suicide attempts among offspring of attempters
vs nonattempters (Generalized Savage: 2 = 7.89; P
= .005; odds ratio, 6.2; 97.5% confidence interval, 1.2-33.4).
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MEASURES OF IMPULSIVITY AND AGGRESSION
The offspring aged 14 years or older of attempters had higher scores
on the BDHI assaultive subscale compared with offspring of nonattempters (4.2
± 2.6 vs 3.3 ± 2.3, t170
= 2.39, P = .02). Similarly, younger offspring of
attempters had higher scores on the CHI assaultive subscale compared with
offspring of nonattempters (8.8 ± 1.4 vs 7.6 ± 1.0, t39 = 2.74, P = .009). However,
there were no differences noted in the BGLHA or either of the measures of
impulsivity (BIS or the Iowa Conners Impulsivity Subscale). Among younger
children, the CBCL scores were not different with respect to total score or
internalizing or externalizing subscales.
FAMILY ENVIRONMENTAL STRESSORS
Proband attempters were more likely to have been exposed to sexual abuse
compared with proband nonattempters (39% vs 18%, 21
= 6.52, P = .01), although there were no differences
between the 2 groups with regard to history of physical abuse (35% vs 35%; P = .96). Neither sexual (9% vs 4%; P = .24) nor physical abuse (9% vs 6%; P =
.41) was more common in offspring of attempters compared with offspring of
nonattempters. Among the subset of offspring living with a parent (n = 93),
offspring of attempters were exposed to lower family cohesion (51.6 ±
11.7 vs 60.9 ± 10.7, t89 = 3.73, P<.001) and lower adaptability (41.1 ± 9.2 vs
45.6 ± 7.4, t88 = 2.41, P<.02) compared with offspring of nonattempters. There were no group
differences on any subscales of the CTS.
RISK FACTORS FOR FAMILIAL TRANSMISSION OF SUICIDAL BEHAVIOR
Nineteen of the offspring attempted suicide, of whom 6 were pairs of
siblings. Offspring who themselves attempted suicide were much more likely
to have a parent who had attempted suicide and who reported a history of sexual
abuse (Table 3). Offspring characteristics
associated with an attempt were female sex; lifetime diagnoses of mood, anxiety,
alcohol or other substance abuse, and cluster B disorder; a history of sexual
abuse; exposure to more psychological aggression; and higher impulsive aggression.
Parent sexual abuse was associated with offspring sexual abuse (OR, 6.4; 97.5%
CI, 1.8-27.5). A mixed-effects logistic regression was conducted, including
site (New York vs Pittsburgh), recruitment source (old vs new sample), and
all the significant variables noted herein, except for offspring cluster B
personality disorder and continuous measures, for which sample sizes were
reduced. Neither site nor recruitment source contributed significantly to
the models. Proband sexual abuse (adjusted OR [AOR], 23.8; 97.5% CI, 2.0-289.5),
offspring sex (AOR, 17.1; 97.5% CI, 1.6-183.6), and offspring alcohol and/or
other substance abuse (AOR, 8.7; 97.5% CI, 1.2-64.6) were significant risk
factors. Analysis of these data using Cox regression yielded nearly identical
results. Of the 19 offspring who attempted suicide, 17 (90%) were the offspring
of suicide attempters, and so risk factors for offspring attempt were examined
just within the offspring of attempters, with very similar results. A logistic
regression conducted with offspring of attempters also identified parental
history of sexual abuse, offspring substance abuse, and offspring female sex
as predictors of familial transmission of suicidal behavior.
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Table 3. Risk Factors for Offspring Suicide Attempt*
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TIMING OF PROBAND AND OFFSPRING ATTEMPT
The relationship between the timing of the most recent parent attempt
and earliest offspring attempt was examined and did not show any evidence
of time clustering. In 4 parent-child pairs, the offspring attempt actually
preceded the parent attempt by 1.8 to 9.4 years. In 4 parent-child pairs,
the offspring attempts occurred more than 20 years after the last parent attempt.
In only 2 parent-offspring pairs did the attempts occur within 12 months of
one another. In addition, there were 3 sibling pairs of attempters whose first
attempts occurred within 10 months, 18 months, and 14 years of one another.
COMMENT
This high-risk family study found a strong and specific familial transmission
of early-onset suicidal behavior from parent to child. Offspring of attempters
had a 6-fold increased risk for a suicide attempt, relative to offspring of
nonattempters, comparable to rates reported in adoption, twin, and family
studies of suicide and suicidal behavior.2, 4-20
An essential but not sufficient component of familial transmission of suicidal
behavior was the transmission of a mood disorder because 82% of familial offspring
suicide attempts occurred in the context of an offspring mood disorder. In
addition to the transmission of a mood disorder, the familial transmission
of suicidal behavior was related to the familial transmission of sexual abuse
and to increased impulsive aggression in offspring.
Sexual abuse in both parent and child played an important role in transmission
of suicidal behavior. A history of reported parental sexual abuse increased
the risk of attempt in offspring, regardless of the offspring's reported abuse
status. In addition, a history of sexual abuse in the proband increased the
likelihood that their offspring would be sexually abused, which in turn was
also associated with increased likelihood of offspring attempt. The intrafamilial
transmission of sexual abuse has been described previously,50
but to our knowledge, this is the first report linking the familial transmission
of reported sexual abuse with the familial transmission of suicide attempt.
At present, we cannot determine how parent and child sexual abuse were related
in this sample, although other studies51-52
suggest that abused parents may be less vigilant and more likely to choose
an abusive partner. Other family environmental correlates of suicide attempt
in offspring, namely, increased parental psychological aggression directed
toward the child and decreased family cohesion, are consistent with previous
reports and are often important family correlates of sexual abuse.51-53
Difficulties with regulation of mood and behavior in parent and offspring
were associated with offspring attempt. Offspring of probands with suicide
attempts showed a greater likelihood to respond to frustration or provocation
with aggression on the BDHI or its downward extension, the CHI, and also showed
a higher prevalence of cluster B personality disorder. Impulsive aggression,
measured dimensionally, and cluster B personality disorder were also associated
with offspring suicide attempt. However, measures of impulsivity alone were
not associated with offspring attempt. These data are consistent with a growing
literature that associates liability to hostility or aggression in the face
of stress, rather than impulsivity, with suicidal behavior.54
Our data are not consistent with imitation as an explanation for parent-to-child
transmission. The time difference between parent and child attempt was highly
variable, with the child attempt preceding the parent attempt in some cases.
Other studies of familial transmission of suicidal behavior are also inconsistent
with imitation. Studies29-30 of
youth exposed to suicide, including siblings, did not find imitation of suicidal
behavior. Twins concordant for suicide attempt show great variability in the
timing of their attempts.19 Adoption studies
do not support a strong role for modeling of suicide within families.4-5
The strengths of this study include a high-risk family design, allowing
assessment of mechanisms of transmission from parent to child, assessment
of key domains likely to be involved in the transmission of suicidal behavior,
and control for mood disorder in both proband groups, so that risk factors
for transmission of suicidal behavior other than mood disorder could be examined.
Our assessment of sexual abuse showed high reliability with few false-negative
results. In this 2-site study, the same risk factors for familial transmission
of suicide attempt were observed at both sites, thereby bolstering the validity
and generalization of these findings.
This study has some limitations. The proband sample, recruited from
inpatient facilities, was clinically severe, so it remains to be determined
whether the findings can be generalized to those with less severe mood disorders.
Therefore, this sample is informative, because of its severity, rather than
representative. However, other family studies6-7,10, 19
that used representative samples of suicide completers and attempters, although
not of a high-risk design, have also found transmission of suicidal behavior.
Because all the probands had mood disorders, we cannot draw conclusions about
the familial transmission of suicidal behavior in those with other mental
disorders, although other studies16, 20
suggest that familial transmission of suicidal behavior occurs in patients
with alcoholism and schizophrenia. Our sample of probands contains very few
male attempters, because male attempters who were inpatients often did not
have access to their children. Consequently, our results are informative about
familial transmission of suicidal behavior from mother to child only. However,
our findings are consistent with family studies2, 4-7,9, 17-18
of mostly male suicide completers. In this article, we only report on the
presence or absence of physical or sexual abuse. More detailed assessment
of abuse and exposure histories are being obtained on follow-up and will be
the subject of future communications. The reliability of our assessment of
physical abuse was only moderate, in keeping with the literature, and this
may have obscured finding a relationship between physical abuse and suicidal
behavior.55 Finally, although the design of
the study is prospective, in this report, we describe solely the cross-sectional
relationships observed.
In conclusion, we have demonstrated familial transmission of suicidal
behavior in a sample of hospitalized adults with mood disorders and their
offspring using a high-risk design. These findings are consistent with previous
adoption, twin, and family studies. In a clinically referred sample, parents
with mood disorders who have made suicide attempts and have been sexually
abused are highly likely to have children who attempt suicide. Conversely,
children with mood disorders are at greater risk for an attempt if they also
show evidence of impulsive aggression, have been sexually abused, and have
parents with the aforementioned risk indicators. These findings provide a
framework for potential targets for treatment and prevention. Future studies
will attempt to validate and extend these observations through the further
prospective follow-up of this cohort.
AUTHOR INFORMATION
Submitted for publication May 16, 2001; final revision received August
15, 2001; Accepted for October 24, 2001.
This work was supported by National Institutes of Mental Health grants
MH56612, MH56390, MH55123, and MH62185.
We thank Anabel Bejarano, PhD, Ainslie Burke, PhD, Shannon Falcone,
MSW, Hope Jacob, MEd, and Kary McPherson, BSN, for conducting interviews;
Joselin Mackily, BA, and Lynn Manalac-Stanley, BS, for completing data cleaning
and management; Laurel Chiappetta, BS, for database development and consultation;
Judith Cohen, MD, for editorial suggestions; and Satish Iyengar, PhD, for
providing statistical consultation. We also thank Beverly Sughrue and Virginia
Howard for their expert assistance in the preparation of this manuscript.
Corresponding author: David A. Brent, MD, 3811 O'Hara St, Suite 112,
Pittsburgh, PA 15213 (e-mail: brentda{at}msx.upmc.edu).
From the Western Psychiatric Institute and Clinic (Drs Brent, Birmaher,
Kolko, and Bridge and Ms Zelazny) and St Francis Medical Center (Dr Salazar),
Pittsburgh, Pa; and New York State Psychiatric Institute, New York City (Drs
Oquendo, Greenhill, Stanley, Brodsky, Ellis, and Mann).
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