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Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Anxiety Reactivity in Daily Life: A Daily Process Approach to Gene-Environment Interaction

From the Department of Psychology (K.C.G.), American University; Department of Psychiatry (T.S.C., J.C., H.R.K.), University of Connecticut School of Medicine; Department of Psychology (S.A.), Fairleigh Dickinson University; Department of Community Medicine (H.T.), University of Connecticut School of Medicine.

Address correspondence and reprint requests to Howard Tennen, Department of Community Medicine, MC 6325 263 Farmington Avenue, Farmington, CT 06030-6325. Email: tennen{at}nso1.uchc.edu

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_AL_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.

Key Words: serotonin transporter • anxiety • stress • reactivity • daily diary

Abbreviations: 5-HTTLPR = serotonin transporter gene promoter polymorphism; 5-HTT = serotonin transporter protein; fMRI = functional magnetic resonance imaging; STAI = State-Trait Anxiety Inventory.

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