Effects of 5-HTTLPR genotype and cognitive rumination on long-term cortisol reactivity measured in human hair

Ample experimental and associative studies have shown that carrying two short (S) alleles of the serotonin transporter gene (5-HTTLPR) contributes to an increased vulnerability for stress and related affective disorders. Recent findings indicate that this relationship might become even more profound when also possessing a negative ruminative (stress-related) thinking style. However, previous studies on the relationship among 5-HTTLPR, stress, and stress-responsiveness almost exclusively measured salivary cortisol concentrations during exposure to a single acute (laboratory) stressor. Measuring cortisol concentrations over longer periods of time might better reflect (chronic) Gene by biological (HPA) stress responsiveness associations. In recent years, the strategy to assess hair cortisol concentration (HCC) has been established as a more reliable marker for chronic HPA activations. The current study explored associations between 3-months accumulated HCC and the tendency to ruminate about negative events in 27 S/S and 27 L/L 5-HTTLPR-carriers (screened from a large n = 827 DNA database). Hierarchical regression (including moderation) analyses revealed clear significant interactions between Genotype and Rumination (p <0.01, f(2)=0.26); indicating greatest accumulation of HCC in high ruminating S/S-allele carriers. These findings implicate that the combined possession of a genetic (S-allele 5-HTTLPR) and cognitive (Rumination) stress-vulnerability might meaningfully increases long-term stress responsiveness; most likely due to increased daily (chronic) stress experiences.Lay summary The current study investigated whether the combined possession of a biological (genetic) and cognitive (negative thinking pattern) stress vulnerability may lead to a greater vulnerability to experience daily stress. This hypothesis was confirmed as a higher accumulation of the cortisol stress hormone was found over the past 3 months in scalp hair of participants that carried both vulnerability factors in combination.