title: Serotonin transporter gene-linked polymorphic region (5-HTTLPR) and diurnal cortisol: A sex by genotype interaction.
abstract: 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.
authors.affiliation: Faculty of Psychology and Neuroscience, Maastricht University, The Netherlands.
authors.forename: Matthis
authors.initials: M
authors.lastname: Wankerl
authors.forename: Birgit-Christiane
authors.initials: BC
authors.lastname: Zyriax
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Kim
authors.initials: K
authors.lastname: Hinkelmann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Windler
authors.forename: Christian
authors.initials: C
authors.lastname: Otte
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012463:Saliva / Q000737:chemistry*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013315:Stress, Psychological / Q000235:genetics; D013997:Time Factors
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone