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The relationship between alcohol consumption, perceived stress, and CRHR1 genotype on the hypothalamic-pituitary-adrenal axis in rural African Americans.

ABSTRACT: OBJECTIVE:Rurally situated African Americans suffer from stress and drug-related health disparities. Unfortunately, research on potential mechanisms that underlie this public health problem have received limited focus in the scientific literature. This study investigated the effects of perceived stress, alcohol consumption, and genotype on the hypothalamic-pituitary-adrenal (HPA) Axis. METHODS:A rural sample of African American emerging adults (n = 84) completed a battery of assessments and provided six samples of salivary cortisol at wakeup, 30 min post wakeup, 90 min post wakeup, 3:00 PM, 3:30 PM, and 4:30 PM. RESULTS:Participants with a TT genotype of the CRHR1 (rs4792887) gene tended to produce the most basal cortisol throughout the day while participants with a CC genotype produced the least amount. Increased levels of perceived stress or alcohol consumption were associated with a blunted cortisol awakening response (CAR). Moreover, the CAR was obliterated for participants who reported both higher stress and alcohol consumption. CONCLUSION:Perceived stress and alcohol consumption had a deleterious effect on the HPA-Axis. Furthermore, genotype predicted level of cortisol production throughout the day. These findings support the need to further investigate the relationship between stress dysregulation, drug-use vulnerability, and associated health disparities that affect this community.

SUBMITTER: Obasi EM

PROVIDER: S-EPMC4471353 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The relationship between alcohol consumption, perceived stress, and CRHR1 genotype on the hypothalamic-pituitary-adrenal axis in rural African Americans.

Obasi Ezemenari M EM Shirtcliff Elizabeth A EA Brody Gene H GH MacKillop James J Pittman Delishia M DM Cavanagh Lucia L Philibert Robert A RA

Frontiers in psychology 20150618

<h4>Objective</h4>Rurally situated African Americans suffer from stress and drug-related health disparities. Unfortunately, research on potential mechanisms that underlie this public health problem have received limited focus in the scientific literature. This study investigated the effects of perceived stress, alcohol consumption, and genotype on the hypothalamic-pituitary-adrenal (HPA) Axis.<h4>Methods</h4>A rural sample of African American emerging adults (n = 84) completed a battery of asses ...[more]

PMID: 26150798

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Project description:CONTEXT:Both highly stress-reactive and novelty-seeking individuals are susceptible to alcohol use disorders. Variation in stress reactivity, exploration, and response to novelty have been attributed to differences in corticotropin-releasing hormone (CRH) system function. As such, CRH gene variation may influence risk for alcohol use and dependence. OBJECTIVE:To determine whether CRH variation influences relevant intermediate phenotypes, behavior, and alcohol consumption in rhesus macaques. DESIGN:We sequenced the rhesus macaque CRH locus (rhCRH) and performed cladistic clustering of haplotypes. In silico analysis, gel shift, and in vitro reporter assays were performed to identify functional variants. Cerebrospinal fluid (CSF) and blood samples were obtained, and levels of CRH and corticotropin (ACTH) were measured by radioimmunoassay. Behavioral data were collected from macaques during infancy. Among adolescent/adult animals, we recorded responses to an unfamiliar conspecific and measured levels of ethanol consumption. SETTING:National Institutes of Health Animal Center. PARTICIPANTS:Rhesus macaques. MAIN OUTCOME MEASURES:Animals were genotyped for a single-nucleotide polymorphism disrupting a glucocorticoid response element, rhCRH -2232 C>G, and the effects of this allele on CSF levels of CRH, plasma levels of ACTH, behavior, and ethanol consumption were assessed by analysis of variance. RESULTS:We show that -2232C>G alters DNA x protein interactions and confers decreased sensitivity of the CRH promoter to glucocorticoids in vitro. Consistent with the known effects of glucocorticoids on CRH expression in the brain, carriers of the G allele had lower CSF levels of CRH but higher levels of ACTH. Infants carrying the G allele were more exploratory and bold, and among adolescent and adult male macaques, the G allele was associated with exploratory/bold responding to an unfamiliar male. Adults with the C/G genotype also exhibited increased alcohol consumption in the social group, a model for high-risk alcohol-seeking behavior. CONCLUSION:Haplotypes that differ in terms of corticosteroid sensitivity have been identified in humans. Our data may suggest that functionally similar CRH variants could influence risk for externalizing disorders in human subjects.

Dataset Information

The relationship between alcohol consumption, perceived stress, and CRHR1 genotype on the hypothalamic-pituitary-adrenal axis in rural African Americans.

Publications

The relationship between alcohol consumption, perceived stress, and CRHR1 genotype on the hypothalamic-pituitary-adrenal axis in rural African Americans.

Similar Datasets

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