Familial Transmission of Suicidal Behavior
Section snippets
Adoption Studies
Three adoption studies have been conducted, all using the same Danish adoption registry (Table 1). Kety and colleagues [2], in a study designed to examine the genetics of schizophrenia and mood disorders, found a nonsignificant trend toward higher concordance for suicide in biological, compared with adoptive relatives of adoptees who committed suicide. Subsequently, a second study compared the rates of suicide among the biological and adoptive relatives of adoptees who committed suicide versus
Twin Studies
In their review of twin case reports for suicide, Roy and Segal [5] found an increased concordance for suicide in monozygotic (MZ) versus dizygotic twins (DZ) (14.9% versus 0.7%), consistent with Tsuang's [6] original observations (Table 3, Table 4). Roy and colleagues [5], [7] found an even higher concordance rate for suicide attempt in the surviving monozygotic twin of the co-twin's suicide in MZ versus DZ twins (38% versus 0%), supporting the view that the clinical phenotype for concordance
Family Studies
Family studies compare the rate of suicide or suicidal behavior in the relatives of a proband with suicidality to the rate of suicide or suicidal behavior in the relatives of probands without suicidality. Studies have varied in outcome (family history of completed suicide, attempted suicide, or both), choice of proband (either completed or attempted suicide), choice of comparison group (community or psychiatric control), and method of assessment of family loading (record review, family history,
Studies of the Risk of Suicide in Probands with Completed Suicide
In studies that examined the familial rates of completed suicide in the relatives of probands who committed suicide, all show an elevated rate of completed suicide in the relatives of completers versus relatives of a comparison group, regardless of whether that comparison group consists of psychiatric, general medical, and community controls (Table 5). Also, these findings are consistent, regardless of whether the probands were drawn from large community pedigrees [14], diagnostically
Population Registry Studies
Four studies using Scandinavian registries report an increased risk of suicide conveyed to a first-degree relative, even after controlling for parental and personal history of inpatient psychiatric treatment (Table 6) [35], [37], [38], [41]. In one study, family history of suicide was associated with an increased rate of suicide even compared with those who have had a first-degree relative die from either accidents or homicides, supporting the view that the familial transmission of suicidal
Family Studies of Suicide Probands and Familial Rates of Suicidal Behavior
Four studies have examined rates of attempted and completed suicide in the families of suicide probands versus the relatives of community controls (Table 7) [23], [24], [28], [40]. Two studies focused on adolescents [23], [24], and two on adults [28], one of which focused exclusively on males [40]. All found an increased rate of suicidal behavior in the relatives of completers compared with relatives of community controls, even after controlling for differences in rates of psychiatric disorder
Family History of Suicidal Behavior in Suicide Attempting Probands
Table 8 lists 12 studies that have examined the rate of suicidal behavior in the families of suicide attempter probands, using a family history method. The findings are very consistent across studies, finding an increased rate of both completed and attempted suicide in the relatives of suicide attempters compared with the family members of controls. These findings are robust across a wide range of conditions: age of attempters (adolescents and adults), sampling frame (community samples,
Family Studies of Suicide-Attempting Probands
Three family studies of child or adolescent suicide-attempting probands have been conducted, finding an increased risk of suicide attempt in the relatives of suicide-attempting probands (Table 9) [21], [25], [26]. These studies also support a definition of the clinical phenotype that includes suicidal behavior, but does not include suicidal ideation, insofar as Pfeffer and colleagues [21] found that a family history of attempts was increased only in the relatives of proband attempters but not
High-Risk Studies
A variant of the family study, the high-risk study, has been used to prospectively examine the risks and processes associated with the familial transmission of suicidal behavior. In three studies that have taken this strategy, results are consistent—offspring of adult mood-disordered suicide attempters have a much higher risk of suicide attempt than offspring of mood-disordered probands who have never made a suicide attempt (Fig. 1). Greater familial loading for suicidal behavior is associated
Possible Mechanisms By Which Familial Transmission of Suicidal Behavior May Occur
Some possible intermediate phenotypes have emerged from family genetic studies. An intermediate phenotype according to Gottesman and Gould [53], must be related to the clinical phenotype, must be heritable, must predict the onset of the condition in offspring, and show evidence of mediation when controlling for the relationship between parent and offspring transmission of the overall clinical phenotype. The intermediate phenotype with the most convergent evidence is impulsive aggression, ie,
Parental Divorce and Separation
There is a large literature documenting a higher risk for suicidal behavior and suicide in children from non-intact families. However, divorce per se is unlikely to lead to suicidal behavior [41], [80], [81]. For example, marital disruption is more common in parents with psychiatric disorder. In studies that have examined the three-way relationships among divorce, parental and child psychiatric disorder, and child suicidal behavior, the relationship between divorce and child suicidal behavior
Summary
It is well recognized that suicidal behavior runs in families. Adoption and twin studies together make a compelling case that familial transmission of suicidal behavior is in part attributable to genetic factors. There is some evidence that the transmission of suicidal behavior is mediated by the transmission of impulsive aggression. Other, less thoroughly investigated possible mediators include neuroticism and neurocognitive deficits. However, given that at best, around 50% of the variance is
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This work was supported by NIMH grants MH 43366, 55123, 6612, 56390, 66371, 62185, and 77930. The expert assistance of Beverly Sughrue in preparation of the manuscript is appreciated.