Serotonin transporter gene polymorphism (5-HTTLPR) and anxiety reactivity in daily life: a daily process approach to gene-environment interaction.

Objective: To test whether individuals with at least one copy of the short (S) or long (L)(G) allele of the serotonin transporter polymorphism (5-HTTLPR) exhibit greater increases in anxiety, compared with L(A)L(A) individuals, under periods of high daily stress. Although this common polymorphism in the serotonin transporter gene has been identified as a vulnerability factor for anxiety, findings in the literature are mixed. Discrepant findings could be explained by recent research showing that 5-HTTLPR is functionally triallelic (L(A) versus L(G) or S), rather than biallelic (L versus S). Mixed findings could also result from a lack of attention to diathesis-stress models, whereby genetic vulnerability is considered latent until activated by stress (gene-environment interplay). Based on this model, we argue that genotype differences in anxiety should be stronger in the presence of stress.

Methods: A total of 350 college students recorded their daily stressors and mood for two 30-day periods, separated by 1 year.

Results: Across both years, diathesis-stress patterns were observed for reports of anxious mood as a function of 5-HTTLPR. Individuals with at least one copy of the S or L(G) allele at 5-HTTLPR experienced elevated anxious mood on days with more intense stressors, as compared with those who were L(A) homozygotes. Genotype differences in anxiety were less apparent on low stress days. No consistent allelic association of 5-HTTLPR was observed with any other mood states, trait anxiety, or neuroticism.

Conclusion: Our findings highlight the potential value of focusing on genetic vulnerability in the context of everyday environmental triggers.