Serotonin transporter polymorphism (5-HTTLPR) is associated with post-awakening cortisol measures in previous depression

Elevated cortisol levels have been linked to major depressive disorder (MDD), but cortisol dynamics vary substantially across individuals and clinical states. Genetic variation in the serotonin transporter polymorphism (5-HTTLPR) has been proposed as one contributor to differences in hypothalamic-pituitary-adrenal axis functioning. The present study examined associations between cortisol awakening measures and 5-HTTLPR genotype groups in individuals with a history of depression compared with healthy controls, and explored whether current depressive symptom severity was related to cortisol indices. A total of 108 individuals with a history of depression were genotyped and compared with 59 healthy controls. Participants completed structured diagnostic interviews and self-reported depressive symptoms. Salivary cortisol was sampled in the evening and at five consecutive timepoints after awakening (15-min intervals). Cortisol was analyzed using a linear mixed-effects model of repeated measures and by cortisol awakening response (CAR) summary indices: area under the curve with respect to ground (AUCg) and area under the curve with respect to increase (AUCi). Cortisol changed significantly over time, but there was no evidence that genotype groups differed in the overall cortisol timecourse. In CAR summary analyses, group differences were observed for AUCg, whereas AUCi did not show corresponding group differences. Regression analyses indicated that BDI-II was not associated with AUCg or AUCi after adjustment for covariates. These findings suggest that 5-HTTLPR-related differences, when present, may be more detectable in overall post-awakening cortisol output than in baseline-relative increase.