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

Abstract

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 identified² and the presence of one or two short alleles was associated with anxiety-related personality traits³ and several psychiatric disturbances, such as affective disorder⁴ 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.