Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion
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.
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.
5-HTTLPR, cortisol awakening response, dexamethasone suppression test, trier social stress test, gender differences
972-982
Wüst, Stefan
530861ea-05ba-4a73-8030-9735f1759d5b
Kumsta, Robert
88285030-6a7c-4ef1-ba75-b78e09cd2f1e
Treutlein, Jens
8fe5a1df-2563-4dd0-a823-4b54e1eb3dac
Frank, Josef
1beb289a-ac15-45fa-9f9b-28afa842f519
Entringer, Sonja
f96a0401-9da9-4f00-aada-b6a3569501ba
Schulze, Thomas G.
d1e5d68c-483e-4e8b-8970-da43ca55bdd4
Rietschel, Marcella
bfe692f6-8ff2-4137-aa33-b28b65710390
August 2009
Wüst, Stefan
530861ea-05ba-4a73-8030-9735f1759d5b
Kumsta, Robert
88285030-6a7c-4ef1-ba75-b78e09cd2f1e
Treutlein, Jens
8fe5a1df-2563-4dd0-a823-4b54e1eb3dac
Frank, Josef
1beb289a-ac15-45fa-9f9b-28afa842f519
Entringer, Sonja
f96a0401-9da9-4f00-aada-b6a3569501ba
Schulze, Thomas G.
d1e5d68c-483e-4e8b-8970-da43ca55bdd4
Rietschel, Marcella
bfe692f6-8ff2-4137-aa33-b28b65710390
Wüst, Stefan, Kumsta, Robert, Treutlein, Jens, Frank, Josef, Entringer, Sonja, Schulze, Thomas G. and Rietschel, Marcella
(2009)
Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.
Psychoneuroendocrinology, 34 (7), .
(doi:10.1016/j.psyneuen.2009.01.011).
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.
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.
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More information
Published date: August 2009
Keywords:
5-HTTLPR, cortisol awakening response, dexamethasone suppression test, trier social stress test, gender differences
Identifiers
Local EPrints ID: 66663
URI: http://eprints.soton.ac.uk/id/eprint/66663
ISSN: 0306-4530
PURE UUID: 79f8cfa1-33b3-4cb4-9ff6-aac5d7e10c75
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Date deposited: 07 Jul 2009
Last modified: 13 Mar 2024 18:28
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Contributors
Author:
Stefan Wüst
Author:
Robert Kumsta
Author:
Jens Treutlein
Author:
Josef Frank
Author:
Sonja Entringer
Author:
Thomas G. Schulze
Author:
Marcella Rietschel
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