Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior

259-264 Background: Dysfunction of serotoninergic transmission could predispose to excessive alcohol consumption and dependence. The functional polymorphism of the serotonin transporter gene (5-HTTLPR) has been associated with different disorders, including alcoholism. Considering the likelihood of heterogeneity in the “alcohol dependence” phenotype, 5-HTTLPR may be more specifically implicated in subsamples of patients or in related traits of alcoholism, such as impulsivity. Methods: We analyzed the role of this functional polymorphism in the risk for suicide attempt in a population of male alcohol-dependent subjects. One hundred ten male alcohol-dependent patients (DSM-III-R criteria), French for at least two generations, were personally interviewed with the Diagnostic Interview for Genetic Studies and compared with 61 unaffected blood donors. Results: The “short” (S) allele of the 5-HTTLPR appeared to be unrelated to alcohol dependence and comorbid depression in our sample, but was found associated with an increased risk for suicide attempts. This association was predominantly observed in severe and repetitive suicide attempts, with a significant dose effect of the S allele (0, 1, or 2) on the number and the severity of suicide attempts. Conclusions: Mood disorders and alcohol dependence may interact with a genetic (relative) deficiency in serotonin reuptake, thereby increasing the risk for aggressive/impulsive behaviors such as suicide attempts.