The short allele of the serotonin transporter gene 5’ promoter region polymorphism (5-HTTLPR) is reported by A. Caspi and others to be associated with susceptibility to depression and suicidality in response to stressful life events. We examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events (SLE) and severity of major depression and suicidality.

Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasians of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism, two low expressing alleles (LG, S) and a higher expressing LA allele. All subjects underwent structured clinical interviews for DSM IV diagnoses, ratings of psychopathology, stressful life events, developmental history and suicidal behavior. Cerebrospinal fluid (CSF) 5-HIAA was assayed in a sub-sample.

Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate-severe life events compared with the LA allele. No associations with suicidal behavior and CSF 5-HIAA were found.

Low expression transporter alleles explain 31% of the variance in major depression severity and increase the impact of stressful life events on severity. The biological phenotype responsible for these effects remains to be elucidated