To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the 'Mannheim Study of Risk Children' (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of > or =0.7% were identified. Both samples were genotyped and systematically examined for association with the htSNPs of CRHR1. In the adolescent sample, significant group differences between genotypes were observed in binge drinking, lifetime prevalence of alcohol intake and lifetime prevalence of drunkenness. The sample of adult alcohol-dependent patients showed association of CRHR1 with high amount of drinking. This is the first time that an association of CRHR1 with specific patterns of alcohol consumption has been reported. Our findings support results from animal models, suggesting an importance of CRHR1 in integrating gene-environment effects in alcohol use disorders.
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Article Synopsis
- Peripuberty is a crucial time for brain development, and blocking CRFR1 receptors in young rats helps minimize negative effects of early-life stress on neural function and behavior.
- In an experiment, male rats showed immediate behavioral changes like reduced prepulse inhibition (PPI) after receiving a CRFR1 antagonist, while females only exhibited differences in behavior after becoming adults.
- Long-term gene expression changes in the amygdala indicate that the effects of CRFR1 blockage during peripuberty impact different neural pathways in males and females, emphasizing the importance of understanding these effects for adolescent mental health.
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