Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.
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.
Wüst
Stefan
S
Department of Theoretical and Clinical Psychobiology, University of Trier, Johanniterufer 15, 54290 Trier, Germany. stefan.wuest@zi-mannheim.de
Kumsta
Robert
R
Treutlein
Jens
J
Frank
Josef
J
Entringer
Sonja
S
Schulze
Thomas G
TG
Rietschel
Marcella
M
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
D003276:Contraceptives, Oral; D050486:Serotonin Plasma Membrane Transport Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone