Serotonin transporter gene-linked polymorphic region (5-HTTLPR) and diurnal cortisol: A sex by genotype interaction.

In interaction with stressful life events, the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with depression. In response to stress, the hypothalamic-pituitary-adrenal (HPA) axis is activated. HPA activity is often increased in depression. Thus, one potential mechanism by which 5-HTTLPR might increase risk for depression is by its impact on HPA activity. We examined the effects of 5-HTTLPR on diurnal saliva cortisol secretion (0800 h, 1200 h, 1600 h, 2200 h) in 130 healthy adults (66 men, 64 women) equally distributed across four age groups (30-70 years) using the tri-allelic classification [high-expressing (LA/LA), intermediate-expressing (LG/LA, LA/S), low-expressing (S/S, S/LG)]. We found a significant sex by 5-HTTLPR interaction on cortisol secretion. In men, higher cortisol levels were associated with lower transcriptional activity of 5-HTTLPR, whereas no such trend was observed in women. Our results suggest that men and women differ in serotonergic mediation of HPA-axis activity. This might contribute to sex-specific risk for depression.