Heterogeneity of the risk of suicidal behavior in bipolar-spectrum disorders

Objectives: The risk of suicidal behavior is substantially elevated in major affective disorders (AD). In bipolar disorder (BD), as many as 15% of patients may commit suicide and family history of suicide is recognized as one of the most important risk factors. Lithium reduces the rates of suicidal behavior in BD, especially in patients who achieve full mood stabilization. Yet even patients who continue experiencing mood episodes do benefit from anti-suicidal properties of lithium. These observations raise questions about the nature of the relationship between the neurobiological mechanisms of BD and suicide, namely whether they are shared or independent. Methods: We studied the distribution of suicides and suicide attempts in 539 subjects from 78 families of probands with major AD, all responders to lithium prophylaxis. A Cox proportional hazard regression model was used to assess the contribution of several independent variables to the risks of AD, BD, and suicidal behavior. Results: The lifetime prevalence of BD was significantly greater among first-degree relatives of suicide than non-suicide probands (22% versus 11%) and the prevalence of BD in families was associated with an increased risk of developing mood disorder and subsequently committing or attempting suicide (p=0.003). Families fell into 1 of 3 groups, corresponding to a low (<0.1%), intermediate (17.8%), and high (87.8%) risk for suicide in affectively ill subjects. Conclusions: Suicidal behavior is distributed unevenly in families of probands with BD, aggregating in a subset of families. Our results also suggest that partially overlapping sets of genetic factors may underlie BD and suicide.