Influence of Comorbid Psychiatric Disorders on the Risk of Development of Alcohol Dependence by Genetic Variations of ALDH2 and ADH1B

Background Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known deterrent to the development of alcohol use disorder (AUD), and however, some individuals with inactiveALDH2do go on to develop AUD. These alcoholics are likely to have strong risk factors for the development of this disorder. Using a model of alcoholics with inactiveALDH2(the AIA model), we investigated the unique characteristics of alcoholics with inactiveALDH2in an attempt to identify the risk factors for AUD. In this study, we focused on comorbid psychiatric and personality disorders as potential risk factors for AUD. Methods The subjects were 103 male alcoholics with inactiveALDH2(AIAs), 87 age- andADH1Bgenotype-matched alcoholics with activeALDH2(AAAs) and 200 age-matched healthy men. The alcoholics were divided into 4 subgroups according to theirALDH2andADH1Bgenotypes (inactiveALDH2vs. activeALDH2, usualADH1Bvs. superactiveADH1B). To assess the participants' comorbid psychiatric disorders, we conducted semi-structured interviews using the Japanese translation of SSAGA version 2. We compared the prevalence of comorbid psychiatric and personality disorders among groups with different combinations of theALDH2andADH1Bgenotypes. Results The prevalence of attention-deficit/hyperactivity disorder (ADHD) was significantly higher in the AIAs with usualADH1Bthan in the other 3 subgroups of alcoholics. In contrast, the prevalence rates of agoraphobia and panic disorder were significantly lower in the AIAs with superactiveADH1Bthan in the other 3 subgroups of alcoholics. Conclusions This study suggested that (i) ADHD is a risk factor for AUD, consistent with previous reports; (ii) agoraphobia and panic disorder may have deterrent effects against the development of AUD in individuals with inactiveALDH2, probably attributable to the similarity between the symptoms of agoraphobia and panic disorder and the adverse reactions to consumption of alcohol in subjects with inactiveALDH2.