History of mental comorbidities and their relationships with drinking milestones, hazardous drug use, suicide attempts, and the ADH1B and ALDH2 genotypes in 4116 Japanese men with alcohol dependence: An exploratory study

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BACKGROUND: Alcohol dependence (AD) is often comorbid with other mental disorders. We assessed how comorbidities are associated with the clinical features of AD. METHODS: Information on the history of mental comorbidities, hazardous drug use, suicide attempts, and drinking milestones was collected on a semi-structured medical history form from 4116 Japanese male AD inpatients (2007-2018); the subjects' ADH1B and ALDH2 genotypes (rs1229984/rs671) were also determined. RESULTS: Of the total, 889 (21.60%) patients reported a history of mental comorbidities, including mood disorders (15.48%) and insomnia (2.89%); 202 (4.91%) reported a history of hazardous drug use, and 614 (14.92%) reported suicide attempts. Comorbidities were most commonly diagnosed around the time of onset of advanced alcohol use disorder (aAUD). Patients with comorbidities who began drinking regularly showed more rapid progression to aAUD and to the start of treatment for AD. Multivariate odds ratios (MORs [95%CI]) for the fast-metabolizing ADH1B*1/*2 and ADH1B*2/*2, protective against AD, were higher in patients with comorbidities [1.43 (1.16-1.76) and 1.35 (1.11-1.66)], drug use [1.64 (1.09-2.46) and 1.60 (1.07-2.38)], and suicide attempts [1.45 (1.13-1.85) and 1.49 (1.17-1.88)] compared with the ADH1B*1/*1. MORs for the inactive protective ALDH2*1/*2 were increased only in patients with insomnia [2.65 (1.75-4.02)] compared with the ALDH2*1/*1. MORs for smoking [0.74 (0.58-0.94)] and for age ≤15 years at first drink [0.66 (0.54-0.81)] were lower in patients with comorbidities. MORs for suicide attempts were 2.87 (2.36-3.48) in patients with comorbidities and 3.38 (2.47-4.62) in patients with drug use. CONCLUSIONS: Mental comorbidities and a history of suicide attempts were frequent in Japanese patients with AD. Risk factors for AD (ADH1B*1/*1, smoking, early initiation of drinking) were negatively associated with the risk of comorbidities, suggesting interactions between comorbidities and AD risk factors. Insomnia was positively associated with the inactive ALDH2*1/*2. AD patients with mental comorbidities require multifaceted interventions, including suicide prevention.

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