This is an R21 developmental application and collaborative international project, designed to strengthen existing cooperative relationships between alcohol researchers in the U.S. and Poland. Its broad, long-term objective is to identify subtypes of alcoholic patients predisposed to relapse, because of genetically determined abnormalities in brain functioning. Thus, it is directly related to NIAAA's mission to conduct research in the areas of genetics and treatment, and to collaborate with international programs engaged in alcohol-related work. It will accomplish its objective by investigating relationships among genetic markers, quantitative EEG activity, impulsivity, and relapse in alcohol-dependent individuals from the U.S. and Poland. Hypothesized relationships among variables, based on literature review and preliminary data, will be tested with an aim to demonstrate feasibility and calculate effect sizes for a larger NIH grant proposal, which would also include larger scale genotyping.
The specific aims are to (1) investigate relationships between impulsivity and relapse in alcohol-dependent subjects; (2) investigate relationships between biological markers of two neurotransmitter systems (serotonin and GABA) and impulsivity in alcohol-dependent subjects; and (3) investigate relationships between genetic and electrophysiological markers of the serotonin and GABA systems and relapse risk in alcohol-dependent subjects. Included in this prospective, naturalistic outcome study are 300 men and women, 18 years of age and over, who meet study criteria for alcohol dependence, and are entering treatment in either Warsaw or Ann Arbor. Visits for structured data collection will occur at intake (baseline) and after 3 and 6 months. The major dependent variable is relapse to alcoholic drinking. Relapse to other drugs of abuse is also considered. The major independent variables are genetic variability in serotonin and GABA neurotransmitter systems (genotypes), fast beta frequency brain activity (endophenotype) as measured by quantitative electroencephalograpy (QEEG), and depressed mood, suicidality, and impulsivity (phenotypes) as measured by validated questionnaires and a computerized stopping task. ? ? ?
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