| Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults. | |
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MedLine Citation:
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PMID: 23274505 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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RATIONALE: Chronic dysregulation of hypothalamus-pituitary-adrenal (HPA) axis activity is related to several neuropsychiatric disorders. Studies suggest that cortisol response to stress has a strong genetic etiology, and that FK506 binding protein 5 (FKBP5) and G-protein coupled type-I CRH receptor (CRHR1) are key proteins regulating response. Variations in the genes encoding these proteins, FKBP5 and CRHR1, have been associated with several neuropsychiatric disorders. OBJECTIVES: We examined variation in these genes in relation to cortisol response to psychological stress in one of the largest Trier Social Stress Test (TSST) cohorts yet examined. METHODS: A total of 368 healthy, young adults underwent the TSST. Salivary cortisol was measured at multiple time points before and after the stressor. Nine variants in FKBP5 and four in CRHR1 were assessed. Single marker analyses were conducted. Secondary analyses assessed haplotypes and interaction with stress-related variables. RESULTS: The strongest association was for rs4713902 in FKBP5 with baseline cortisol (p (dom) = 0.0004). We also identified a male-specific effect of FKBP5 polymorphisms on peak response and response area under the curve (p = 0.0028 for rs3800374). In CRHR1, rs7209436, rs110402, and rs242924 were nominally associated with peak response (p (rec) = 0.0029-0.0047). We observed interactions between trait anxiety and rs7209436 and rs110402 in CRHR1 in association with baseline cortisol (p (LRT) = 0.0272 and p (LRT) = 0.0483, respectively). CONCLUSIONS: We show association of variants in FKBP5 and CRHR1 with cortisol response to psychosocial stress. These variants were previously shown to be associated with neuropsychiatric disorders. These findings have implications for interindividual variation in HPA axis activity and potentially for the etiology of neuropsychiatric disorders. |
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Authors:
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Pamela Belmonte Mahon; Peter P Zandi; James B Potash; Gerald Nestadt; Gary S Wand |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-30 |
Journal Detail:
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Title: Psychopharmacology Volume: - ISSN: 1432-2072 ISO Abbreviation: Psychopharmacology (Berl.) Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7608025 Medline TA: Psychopharmacology (Berl) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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The Johns Hopkins Mood Disorders Center, Baltimore, MD, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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