title: Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Theoretical and Clinical Psychobiology, University of Trier, Johanniterufer 15, 54290 Trier, Germany. stefan.wuest@zi-mannheim.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Wüst
authors.forename: Robert
authors.initials: R
authors.lastname: Kumsta
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Josef
authors.initials: J
authors.lastname: Frank
authors.forename: Sonja
authors.initials: S
authors.lastname: Entringer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000328:Adult; D003276:Contraceptives, Oral / Q000008:administration & dosage; D003907:Dexamethasone / Q000097:blood / Q000494:pharmacology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000502:physiology; D012463:Saliva / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D003276:Contraceptives, Oral; D050486:Serotonin Plasma Membrane Transport Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone