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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.

The article reviews the existing evidence and the concept of the anti-suicidal effect of lithium long-term treatment in bipolar patients. The core studies supporting the concept of a suicide preventive effect of lithium in bipolar patients come from the international research group IGSLI, from Sweden, Italy, and recently also from the U.S. Patients on lithium possess an eight- time lower suicide risk than those off lithium. The anti-suicidal effect is not necessarily coupled to lithium's episode suppressing efficacy. The great number of lives potentially saved by lithium adds to the remarkable benefits of lithium in economical terms. The evidence that lithium can effectively reduce suicide risk has been integrated into modern algorithms in order to select the optimal maintenance therapy for an individual patient.

The suicide-related mortality among patients with affective disorders is approximately 30 times higher, and overall mortality 2 to 3 times higher, than suicide-related mortality in the general population. Lithium has demonstrated possibly specific antisuicidal effects apart from its prophylactic efficacy: it significantly reduces the high excess mortality of patients with affective disorders. To date, suicide-prevention effects have not been shown for antidepressant or anticonvulsant long-term treatment. Clozapine appears to reduce the suicide rate in schizophrenia patients. Against this background, guidelines and algorithms for selecting an appropriate prophylactic strategy for affective disorders should consider the presence of suicidality in patient history. Appropriate lithium prophylaxis prevents approximately 250 suicides yearly in Germany, although lithium salts are infrequently prescribed within the National Health Scheme (specifically, to 0.06% of the population). Rational treatment strategies most likely would demand that prescription rates be about 10 times higher.

Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented. [ABSTRACT FROM AUTHOR]

Tests for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. Linkage and association strategies in identifying genes of major effect; Role of etiologic heterogeneity; Impact of the combination of linkage and association strategies on detecting true gene effects.