Bach P1, Vollstädt-Klein S1, Kirsch M1, Hoffmann S1, Jorde A1, Frank J2, Charlet K3, Beck A3, Heinz A3, Walter H4, Sommer WH1,5, Spanagel R5, Rietschel M2, Kiefer F1
1 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany
2 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany
3 Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin, Berlin, Germany
4 Division of Mind and Brain Research, Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin, Berlin, Germany
5 Institute of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Germany
The risk to develop an alcohol addiction is influenced by environmental and genetic factors. Recently, genetic polymorphisms in the glutamate and opioid receptor genes have been found to be associated with alcohol dependence risk. Those receptors are of special interest, because they are targets of therapeutic agents such as acamprosate and topiramate. However, the role of these genetic markers on neural response to alcohol, behavior and relapse risk remains to be determined. Several studies were conducted, in order to investigate the effects of genetic polymorphisms in the mu-opioid receptor gene OPRM1 and in the glutamate receptor genes GRIK1, GRIN1, GRIN2A, GRIN2C on alcohol cue-induced brain response, addictive behavior and relapse risk in samples of alcohol dependent patients. Experimental procedures included functional magnetic resonance imaging, neuropsychological testing and follow-up investigations. Data on clinical parameters, alcohol craving, neural response to alcohol cues and relapse risk was collected and analyzed. Results demonstrate effects of polymorphisms in glutamate and opioid receptor genes on alcohol cue-induced brain response in frontal and mesolimbic brain areas, subjective craving and time to first relapse. Current findings extend existing knowledge about the contribution of genetic effects to addictive behavior, treatment outcome and patient stratification. The investigation of genetic risk factors and mechanisms by which they affect addiction related phenotypes seems to be a promising tool to identify molecular treatment targets and predictors for successful treatment strategies.