Elsevier

Biological Psychiatry

Volume 63, Issue 2, 15 January 2008, Pages 146-151
Biological Psychiatry

Original Article
Interaction between CRHR1 Gene and Stressful Life Events Predicts Adolescent Heavy Alcohol Use

https://doi.org/10.1016/j.biopsych.2007.04.026Get rights and content

Background

Recent animal research suggests that alterations in the corticotropin releasing hormone receptor 1 (CRHR1) may lead to heavy alcohol use following repeated stress. The aim of this study was to examine interactions between two haplotype-tagging single nucleotide polymorphisms (SNPs) covering the CRHR1 gene and adverse life events on heavy drinking in adolescents.

Methods

Data were available from the Mannheim Study of Children at Risk, an ongoing cohort study of the long-term outcome of early risk factors followed since birth. At age 15 years, 280 participants (135 males, 145 females) completed a self-report questionnaire measuring alcohol use and were genotyped for two SNPs (rs242938, rs1876831) of CRHR1. Assessment of negative life events over the past three years was obtained by a standardized interview with the parents.

Results

Adolescents homozygous for the C allele of rs1876831 drank higher maximum amounts of alcohol per occasion and had greater lifetime rates of heavy drinking in relation to negative life events than individuals carrying the T allele. No gene × environment interactions were found for regular drinking and between rs242938 and stressful life events.

Conclusions

These findings provide first evidence in humans that the CRHR1 gene interacts with exposure to stressful life events to predict heavy alcohol use in adolescents.

Section snippets

Participants

Participants were selected from the Mannheim Study of Children at Risk, a large-scale prospective longitudinal study of the outcome of early risk factors from infancy into adolescence (10). The initial sample comprised 384 children of predominantly (>99.0%) European descent born between 1986–1988. Infants were recruited from two obstetric and six children’s hospitals of the Rhine-Neckar Region of Germany and were included consecutively into the sample according to a two-factorial design

Results

Table 1 presents descriptive data for the drinking and life events measures in the total sample and separately for each genotype. Bivariate comparisons adjusted for sex revealed significant differences between genotype groups. Adolescents homozygous for the C allele of rs1876831 exhibited both higher regular and heavy alcohol use than those carrying the T allele. In addition, carriers of the A allele of rs242938 reported significantly more lifetime heavy drinking than homozygotes for the G

Discussion

This study is the first to provide evidence in humans that genetic variation in CRHR1 moderates the impact of stress on heavy drinking, revealing an effect of negative life events only among individuals carrying a particular genotype of this gene. Specifically, our results indicated that, among 15-year-olds homozygous for the C allele of a haplotype tagging single nucleotide polymorphism (rs1876831) of CRHR1, the number of negative life events during the past three years was significantly

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