Stressing over anxiety: A novel interaction of 5-HTTPLR genotype and anxiety-related phenotypes in older adults

Variation within the serotonin transporter gene-linked polymorphic region (5-HTTPLR) contributes to individual differences in trait neuroticism and increases risk for the development of psychopathology in the context of stressful life events. The underlying mechanisms may involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of stress-related hormones. Yet, observed effects are small, possibly because they occur against the background of many other, mostly unknown, genetic and environmental variables. In this study, we removed much of the variance contributed by such background factors by including complex trait and behavioral measures in our analyses, to isolate the unique contributions of 5-HTTLPR genotype to cortisol baseline, reactivity, and recovery during the Trier Social Stress Test. We recruited 82 community-dwelling older adults (55 and older), an under-studied population, and measured salivary cortisol levels at baseline and following the TSST. As a comparison group we also recruited 88 younger adults (males only, 18-51 years old). Neuroticism, trait anxiety, perceived stress levels, and early childhood trauma experiences were measured using self-report questionnaires. An exploratory factor analysis revealed a latent anxiety trait. Cortisol baseline levels were significantly elevated in older adult S-allele carriers (but not in LL-homozygotes) who scored higher on the latent anxiety trait, relative to S-allele carriers. No such differences were found among younger adults, nor amongst measures obtained during the reactivity or recovery periods. These results highlight the utility of taking into account background variables that may otherwise obscure associations between genetic variables and endophenotypes.