Document Detail


Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults.
MedLine Citation:
PMID:  23274505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pamela Belmonte Mahon; Peter P Zandi; James B Potash; Gerald Nestadt; Gary S Wand
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-30
Journal Detail:
Title:  Psychopharmacology     Volume:  227     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-10-28     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  231-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Female
Humans
Hydrocortisone / metabolism*
Hypothalamo-Hypophyseal System / metabolism
Male
Pituitary-Adrenal System / metabolism
Polymorphism, Single Nucleotide
Psychological Tests
Receptors, Corticotropin-Releasing Hormone / genetics*
Saliva / metabolism
Sex Factors
Stress, Psychological / genetics,  physiopathology*
Tacrolimus Binding Proteins / genetics*
Time Factors
Young Adult
Grant Support
ID/Acronym/Agency:
K05 AA020342/AA/NIAAA NIH HHS; K05AA020342/AA/NIAAA NIH HHS; R01 AA010158/AA/NIAAA NIH HHS; R01 MH076953/MH/NIMH NIH HHS; R01MH076953/MH/NIMH NIH HHS; U01 AA020890/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/CRF receptor type 1; 0/Receptors, Corticotropin-Releasing Hormone; EC 5.2.1.-/Tacrolimus Binding Proteins; EC 5.2.1.8/tacrolimus binding protein 5; WI4X0X7BPJ/Hydrocortisone
Comments/Corrections

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