Original ArticleInteraction between CRHR1 Gene and Stressful Life Events Predicts Adolescent Heavy Alcohol Use
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
References (32)
- et al.
Behavioral sequelae of perinatal insults and early family adversity at 8 years of age
J Am Acad Child Adolesc Psychiatry
(2000) - et al.
Reliability of life event assessments: test-retest reliability and fall-off effects of the Munich Interview for the Assessment of Life Events and Conditions
J Affect Disord
(1989) - et al.
Life events and changes in the course of depression in young adults
Eur Psychiatry
(2002) - et al.
Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use
Biol Psychiatry
(2007) - et al.
Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder
Biol Psychiatry
(2006) - et al.
Lack of association between single nucleotide polymorphisms in the corticotropin releasing hormone receptor 1 (CRHR1) gene and alcohol dependence
J Psychiatr Res
(2005) - et al.
The stressful life events schedule for children and adolescents: development and validation
Psychiatry Res
(2003) Stress and alcohol interaction: an update of human research
Alcohol Clin Exp Res
(1991)- et al.
The association between stress and drinking: modifying effects of gender and vulnerability
Alcohol Alcohol
(2005) Genetics of alcohol and tobacco use in humans
Ann Med
(2003)
Do centrally administered neuropeptides access cognate receptors?: an analysis in the central corticotropin-releasing factor system
J Neurosci
A chilled-out knockout
Nat Genet
Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress
Proc Natl Acad Sci U S A
Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples
Mol Psychiatry
Up-regulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala Crhr 1 expression following a history of dependence
Biol Psychiatry
3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl- imidazo[1,2-b]pyridazine: a novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism
J Neurosci
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