Serotonin transporter gene variants and prediction of stress-induced risk for psychological distress.

The response to psychosocial stress is influenced by both psychosocial factors and genetic vulnerability. The most investigated gene in gene × environment studies in abnormal response to environmental stressors is the one coding for the serotonin transporter (SLC6A4). Variability within this gene has been associated with functional brain differences, personality dimensions, reactivity to stress and risk for various psychopathological conditions. In the present study, we set out to investigate the association of common genetic variants within SLC6A4 with state psychopathology in a community sample homogeneously exposed to stress, thus inquiring about potential genetic differences in stress sensitivity. One thousand eight hundred seventy-five young conscripts were evaluated for psychopathological distress with the 90-item Symptoms Checklist Revised in their first 2 weeks of admission to obligatory military service. Of these, 1594 were genotyped for the biallelic ins/del polymorphism (5-HTTLPR S/L) within the promoter region of SLC6A4, as well as the variation within the 'long' 5-HTTLPR allele (rs25531A/G). Homozygous for the 5-HTTLPR S allele reported significantly higher scores for paranoid ideation as compared with L-allele carriers. Slight effects on other subscales were observed, but were not significant after correction for multiple testing. Despite limitations linked to the evaluation of psychopathology by a single general scale and multiple comparisons, the present study support a role of SLC6A4 in modulating abnormal responses to environmental stress. In particular, variation within this gene may confer risk for paranoid/defensive reactions under conditions of environmental stress associated with military induction.