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Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults.

ABSTRACT: 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.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.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.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).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.

SUBMITTER: Mahon PB

PROVIDER: S-EPMC3628278 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults.

Mahon Pamela Belmonte PB Zandi Peter P PP Potash James B JB Nestadt Gerald G Wand Gary S GS

Psychopharmacology 20121230 2

<h4>Rationale</h4>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.<h4>Objectives</h4>W ...[more]

PMID: 23274505

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Project description:As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one's time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms) and long (1,600 ms) visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group), individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the understanding of the relationship between stress and temporal sensitivity.

Dataset Information

Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults.

Publications

Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults.

Similar Datasets

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