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Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood

  • Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment asRecent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. (C) 2013 Elsevier B.V. and ECNR This is an open access article under the CC BY-NC-ND license.show moreshow less

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Author:Arlette F. Buchmann, Nathalie Holz, Regina Boecker, Dorothea Blomeyer, Marcella Rietschel, Stephanie H. Witt, Martin H. Schmidt, Günter EsserGND, Tobias Banaschewski, Daniel Brandeis, Ulrich S. Zimmermann, Manfred Laucht
DOI:https://doi.org/10.1016/j.euroneuro.2013.12.001
ISSN:0924-977X (print)
ISSN:1873-7862 (online)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24411633
Parent Title (English):European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Year of first Publication:2014
Year of Completion:2014
Release Date:2017/03/27
Tag:Childhood adversity; Cortisol; FKBP5; HPA; Stress
Volume:24
Issue:6
Pagenumber:9
First Page:837
Last Page:845
Funder:National Genome Research Network
Organizational units:Humanwissenschaftliche Fakultät / Institut für Psychologie
Peer Review:Referiert