ArticleArchives of general psychiatry2008
CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques.
Article in Archives of general psychiatry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 63 citations in OpenAlex.
- Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Stress (Amsterdam, Netherlands) · 2024Article
- Resilience to Stress: Lessons from Rodents about Nature versus Nurture.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2022Review
- CRF modulation of central monoaminergic function: Implications for sex differences in alcohol drinking and anxiety.Alcohol (Fayetteville, N.Y.) · 2018Review
- Low Inherent Sensitivity to the Intoxicating Effects of Ethanol in Rhesus Monkeys with Low CSF Concentrations of the Serotonin Metabolite 5-Hydroxyindoleacetic Acid.Alcoholism, clinical and experimental research · 2018Article
- HPA Axis Genes, and Their Interaction with Childhood Maltreatment, are Related to Cortisol Levels and Stress-Related Phenotypes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- OPRM1 genotype interacts with serotonin system dysfunction to predict alcohol-heightened aggression in primates.Addiction biology · 2017Article
- Influence of stress associated with chronic alcohol exposure on drinking.Neuropharmacology · 2017Review
- Don't stress about CRF: assessing the translational failures of CRFPsychopharmacology · 2017Review
- Intermittent Access to Ethanol Induces Escalated Alcohol Consumption in Primates.Journal of addictive behaviors, therapy & rehabilitation · 2017Article
- Studying longitudinal trajectories in animal models of psychiatric illness and their translation to the human condition.Neuroscience research · 2016Review
- NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking.Nature neuroscience · 2015Article
- Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation.Genes, brain, and behavior · 2015Review
- Quantitative Genetics of Response to Novelty and Other Stimuli by Infant Rhesus Macaques (International journal of primatology · 2014Article
- Neurochemical mechanisms of alcohol withdrawal.Handbook of clinical neurology · 2014Review
- Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge.Translational developmental psychiatry · 2013Article
- The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.ILAR journal · 2013Review
- Nonhuman primate models in the genomic era: a paradigm shift.ILAR journal · 2013Review
- Genetic load is associated with hypothalamic-pituitary-adrenal axis dysregulation in macaques.Genes, brain, and behavior · 2012Article
- Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys.Psychopharmacology · 2012Article
- Pathway based analysis of genotypes in relation to alcohol dependence.The pharmacogenomics journal · 2012Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
contextBoth 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.
objectiveTo determine whether CRH variation influences relevant intermediate phenotypes, behavior, and alcohol consumption in rhesus macaques.
designWe 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.
settingNational Institutes of Health Animal Center.
participantsRhesus macaques.
main outcome measuresAnimals 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.
resultsWe 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.
conclusionHaplotypes 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.
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