Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide

There is abundant evidence that the serotonin (5-HT) system is modulating mood and several behavioural traits and that disturbances in the regulation of this system can be associated with severe behavioural malfunctions, as aggressive implusive and suicidal behaviour.(1) Recently a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was identified(2) and the presence of one or two short alleles was associated with anxiety-related personality traits(3) and several psychiatric disturbances, such as affective disorder(4) or severe alcohol dependence.(5) With respect to the importance of the 5-HT transporter in serotonergic transmission, we have genotyped the DNA of 58 Caucasian suicide victims (with unknown psychiatric diagnoses) and 110 healthy controls for the biallelic functional polymorphism in the 5-HTTLPR. We found a highly significant increased frequency of suicide victims being carriers of one or two short alleles (Fisher's Exact Test, two sided, P = 0.0003), which suggests that a genetically altered protein function within the serotonergic pathway might be involved in suicidality, independently from the clinical diagnosis.