OBJECTIVE: A key regulator of serotonergic neurotransmission is the serotonin transporter (5-HTT) and a common 5HTT gene promoter polymorphism, termed 5HTTLPR, is associated with phenotypes related to anxiety and depression. Furthermore, the serotonergic system influences hypothalamus-pituitary-adrenal (HPA) axis activity, which, in turn, is related to psychiatric diseases. METHODS: To explore the association between the 5-HTTLPR and HPA axis regulation we performed a detailed endophenotyping in 216 healthy subjects (all 126 females used oral contraceptives). RESULTS: While ACTH and cortisol responses to an established psychosocial stress paradigm (Trier Social Stress Test) were not found to be related to the 5-HTTLPR, we observed a significant and sex-specific association with the cortisol awakening response, which is a reliable marker of basal cortisol secretion, and with ACTH levels after dexamethasone administration. The supplementary inclusion of a 5-HTT A/G polymorphism (rs25531) in the analyses did not substantially modify our results. CONCLUSION: These findings support the view that the 5-HTTLPR is associated with a major neuroendocrine stress system. It could be speculated that the sex-specific nature of this association contributes to the distinct gender differences in the vulnerability for depression.
OBJECTIVE: A key regulator of serotonergic neurotransmission is the serotonin transporter (5-HTT) and a common 5HTT gene promoter polymorphism, termed 5HTTLPR, is associated with phenotypes related to anxiety and depression. Furthermore, the serotonergic system influences hypothalamus-pituitary-adrenal (HPA) axis activity, which, in turn, is related to psychiatric diseases. METHODS: To explore the association between the 5-HTTLPR and HPA axis regulation we performed a detailed endophenotyping in 216 healthy subjects (all 126 females used oral contraceptives). RESULTS: While ACTH and cortisol responses to an established psychosocial stress paradigm (Trier Social Stress Test) were not found to be related to the 5-HTTLPR, we observed a significant and sex-specific association with the cortisol awakening response, which is a reliable marker of basal cortisol secretion, and with ACTH levels after dexamethasone administration. The supplementary inclusion of a 5-HTT A/G polymorphism (rs25531) in the analyses did not substantially modify our results. CONCLUSION: These findings support the view that the 5-HTTLPR is associated with a major neuroendocrine stress system. It could be speculated that the sex-specific nature of this association contributes to the distinct gender differences in the vulnerability for depression.
Authors: R Parrish Waters; Marion Rivalan; D A Bangasser; J M Deussing; M Ising; S K Wood; F Holsboer; Cliff H Summers Journal: Neurosci Biobehav Rev Date: 2015-08-10 Impact factor: 8.989
Authors: H Welper; A Aller; V Guttenthaler; S Höfels; L Lennertz; U Pfeiffer; S G Schwab; A Zobel Journal: Nervenarzt Date: 2014-03 Impact factor: 1.214
Authors: Anne N Banducci; Melissa Gomes; Laura MacPherson; C W Lejuez; Marc N Potenza; Joel Gelernter; Ananda B Amstadter Journal: Psychol Trauma Date: 2014-01-01
Authors: Carolyn A Fredericks; Emily M Drabant; Michael D Edge; Jean M Tillie; Joachim Hallmayer; Wiveka Ramel; Janice R Kuo; Sean Mackey; James J Gross; Firdaus S Dhabhar Journal: Brain Behav Immun Date: 2009-10-31 Impact factor: 7.217