Journal
PSYCHONEUROENDOCRINOLOGY
Volume 42, Issue -, Pages 89-97Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2014.01.007
Keywords
Hypothalamic-pituitary-adrenal axis; FK506 binding protein 5; Polymorphism; Post-traumatic stress disorder; Dexamethasone/corticotropin-releasing hormone test; Glucocorticoid receptor; Age-dependent
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Funding
- Japan Society for the Promotion of Science (JSPS) [23791371, 20790870]
- Japan Human Sciences Foundation
- JST, CREST
- Intramural Research Grant for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry, Japan [24-11]
- Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan [10102837]
- Grants-in-Aid for Scientific Research [25861041, 23791371, 20790870] Funding Source: KAKEN
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Regulation of hypothalamic-pituitary-adrenal (HPA) axis reactivity plays an important role in the development of stress-related psychiatric disorders. FK506 binding protein 5 (FKBP5) modulates HPA axis reactivity via glucocorticoid receptor (GR; NR3C1) sensitivity and signaling. The T allele of the single nucleotide polymorphism, FKBP5 rs1360780 (C/T), is associated with higher FKBP5 induction by glucocorticoids. In the present study, we performed the dexamethasone/corticotropin releasing hormone (DEX/CRH) test and quantitative real-time PCR analysis of peripheral blood mononuclear cell (PBMC) cDNA samples in 174 and 278 non-clinical individuals, respectively. We found increased suppression of the stress hormone (cortisol) response to the DEX/CRH test (P = 0.0016) in aged (>50 years) individuals carrying the Tallele compared with aged non-T allele carriers. Tcarriers showed significant age-related changes in GR and FKBP5 mRNA expression levels in PBMCs (P = 0.0013 and P = 0.00048, respectively). Our results indicate that FKBP5 rs1360780 regulates HPA axis reactivity and expression levels of GR and FKBP5 in PBMCs in an age-dependent manner. Because these phenotypes of aged Tcarriers are similar to endophenotypes of people with post-traumatic stress disorder, our findings may be useful for determining the molecular mechanisms, treatment, and preventive strategies for this disease. (C) 2014 Elsevier Ltd. All rights reserved.
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