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Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

Authors

  • Marcin Wojnar,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Kirk J. Brower,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Stephen Strobbe,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Mark Ilgen,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Halina Matsumoto,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Izabela Nowosad,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Elzbieta Sliwerska,

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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  • Margit Burmeister

    1. From the Department of Psychiatry (MW, KJB, SS, MI, MB), Molecular & Behavioral Neuroscience Institute (ES, MB), University of Michigan, Ann Arbor, Michigan; Department of Psychiatry, Medical University of Warsaw (MW, HM, IN), Warsaw, Poland; Department of Veterans Affairs (MI), Health Services Research & Development, Ann Arbor, Michigan.
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Reprint requests: Marcin Wojnar, MD, PhD, University of Michigan Addiction Research Center, Rachel Upjohn Building, 4250 Plymouth Road, Ann Arbor, MI 48109; Fax: 734-998-7992; E-mail: mwojnar@umich.edu

Abstract

Background:  The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients.

Methods:  The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures.

Results:  Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger.

Conclusions:  The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.

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