The International Journal of Neuropsychopharmacology

Research Article

Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds

Brigitte Schmida1, Dorothea Blomeyera1, Jens Treutleina2, Ulrich S. Zimmermanna3a4, Arlette F. Buchmanna1a4, Martin H. Schmidta1, Günter Essera5, Marcella Rietschela2, Tobias Banaschewskia1, Gunter Schumanna6 and Manfred Lauchta1a5 c1

a1 Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

a2 Molecular Genetics Laboratory, Central Institute of Mental Health, Mannheim, Germany

a3 Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden, Germany

a4 Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany

a5 Department of Psychology, Division of Clinical Psychology, University of Potsdam, Potsdam, Germany

a6 Section of Addiction Biology, Division of Psychological Medicine, Institute of Psychiatry, King's College, London, UK

Abstract

Research in animals and first results in adolescents have indicated that genetic variation in the corticotropin-releasing hormone receptor 1 (CRHR1) is associated with heavy alcohol consumption related to stress. The purpose of this study was to determine whether two haplotype-tagging single nucleotide polymorphisms covering the CRHR1 gene (rs242938, rs1876831) interact with stressful life events affecting age at drinking initiation and alcohol consumption in young adults. Participants were drawn from the Mannheim Study of Children at Risk, an epidemiological cohort study following the outcome of early risk factors. Structured interviews were administered to 270 participants (125 males, 145 females) at 15 yr and 19 yr to assess age at first drinking and, at 19 yr, to assess current drinking and recent stressful life events. Life events during childhood and child psychopathology were measured using standardized parent interviews. Results indicated that, even after control for a range of confounders, higher numbers of stressful life events prior to drinking onset were significantly related to earlier age at first drink only among homozygotes for the C allele of rs1876831. Earlier age at drinking onset was significantly associated with higher consumption levels in 19-yr-olds. Furthermore, homozygotes of the rs1876831 C allele as well as carriers of the rs242938 A allele, when exposed to stress, exhibited significantly higher drinking activity than carriers of other alleles. These findings extend previous reports by demonstrating that the CRHR1 gene and stressful life events interact to predict both drinking initiation in adolescence and progression of heavy alcohol use in young adulthood.

(Received September 25 2008)

(Reviewed October 28 2008)

(Revised May 19 2009)

(Accepted June 12 2009)

(Online publication July 17 2009)

Correspondence:

c1 Address for correspondence: Prof. Dr. M. Laucht, Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. Tel.: +49 621/1703-4903 Fax: +49 621/1703-1205 Email: manfred.laucht@zi-mannheim.de

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