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Excessive alcohol use is a leading cause of global morbidity and premature mortality. This study evaluated the effectiveness of two types of nurse-delivered interventions to reduce excessive alcohol consumption among screened participants using the alcohol use disorders identification test (AUDIT) in the workplace.A randomized controlled trial involving AUDIT-positive employees of five Japan-based companies was conducted. A total of 351 participants were randomized into groups that received a patient information leaflet (PIL), 5 min of brief advice, or 15 min of brief advice and counseling. Outcomes (weekly alcohol consumption and drinking and binge drinking frequency in the previous 30 days) were evaluated at 6 and 12-month follow-up.The follow-up rates were 96.3% (n = 338) and 94.9% (n = 333) at 6 and 12 months, respectively. At 6 months, the mean change in weekly alcohol consumption was -38.1 g (-1.64 US fluid oz/week) in the 15-min brief advice and counseling group, which differed significantly from the PIL group. The reduction in the advice and counseling group persisted at 12-month follow-up but was no longer significantly different from the PIL group. There was no significant change in alcohol consumption observed in the 5-min brief advice group. Improvement in drinking and binge drinking frequency was observed in all three groups.Nurse-delivered 15-min brief advice and counseling was effective over a 6-month period in reducing alcohol consumption in a workplace setting. This finding suggests that the implementation of workplace screening and brief intervention could play a useful role in preventing the burden of harmful alcohol use.

BACKGROUND While accumulating evidence suggests a relation between the severity of alcohol dependence and the risk of its recurrence, the impact of dependence severity on the course of the disorder has not been carefully evaluated. The present study examined the impact of several severity indices of alcohol dependence on the drinking course after inpatient treatment. METHODS This prospective study was conducted over a 12-month period following alcohol treatment at a specialized hospital. A total of 712 consecutively admitted alcohol-dependent patients were targeted for enrollment at the time of their hospitalization, with 637 patients registered and followed. The characteristics and severity of the subjects were assessed using multiple methods at admission, with their course after discharge followed continuously using mailed questionnaires that queried them regarding their drinking behavior. RESULTS Greater severity of dependence, assessed using the number of ICD-10 diagnostic criteria met, was associated with a lower rate of abstinence during the study period (p = 0.035). The rate of abstinence also decreased significantly as the baseline blood gamma-glutamyl transferase value and Alcohol Dependence Scale (ADS) score increased (p = 0.031 and p = 0.0002, respectively). In multivariate Cox proportional hazards analyses, the group with the most severe ADS scores had a significantly greater risk of relapse to drinking than the group with the least severe scores (HR = 2.67, p = 0.001). Dependence severity also associated with the drinking pattern; participants in both the controlled drinking group and the abstinence group had lower ADS scores at admission and a later age at first drinking (p = 0.001 and p

Background Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known deterrent to the development of alcohol use disorder (AUD), and however, some individuals with inactive ALDH2 do 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 inactive ALDH2 (the AIA model), we investigated the unique characteristics of alcoholics with inactive ALDH2 in 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 inactive ALDH2 (AIAs), 87 age- and ADH1B genotype-matched alcoholics with active ALDH2 (AAAs) and 200 age-matched healthy men. The alcoholics were divided into 4 subgroups according to their ALDH2 and ADH1B genotypes (inactive ALDH2 vs. active ALDH2, usual ADH1B vs. superactive ADH1B). 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 the ALDH2 and ADH1B genotypes. Results The prevalence of attention-deficit/hyperactivity disorder (ADHD) was significantly higher in the AIAs with usual ADH1B than in the other 3 subgroups of alcoholics. In contrast, the prevalence rates of agoraphobia and panic disorder were significantly lower in the AIAs with superactive ADH1B than 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 inactive ALDH2, probably attributable to the similarity between the symptoms of agoraphobia and panic disorder and the adverse reactions to consumption of alcohol in subjects with inactive ALDH2.

Alcohol use disorder is a common and complex disorder with a well-documented highly hereditary nature (Higuchi et al., 2006; Roh et al., 2008). Subjective response to alcohol is also known to be a genetically influenced characteristic (Schuckit et al., 2007; Viken et al., 2003). This suggests that genetic influences on individual variation in subjective response to alcohol may underlie the effects of genes on alcohol-related disorders. A low level of response to the acute effects of alcohol has been associated with an increased risk of both excessive alcohol intake (Hinckers et al., 2006; Schuckit et al., 2007) and alcohol dependence (Schuckit, 1994; Schuckit and Smith, 1996; Schuckit et al., 2004), which are well known to be highly heritable (Kendler, 2001). There is consistent evidence that the GABAA receptor regulates the alcohol self-administration in animal models, probably by stimulating reward circuitry in the mesolimbic system (Chester and Cunningham, 2002; Eiler and June, 2007; Harvey et al., 2002; June et al., 2003). Several GABAA receptor subunits have been implicated in alcohol effects, so that the specific subunit composition of the receptor may be an important determinant of alcohol’s CNS effects. The α2 subunit of the GABAA receptor mediates the anxiolytic effects of benzodiazepines (Low et al., 2000; Rudolph et al., 1999) and enhances the hypnotic, but not the sedative, effects of combined exposure to alcohol and benzodiazepines (Tauber et al., 2003). Two genome-wide scans in humans have provided evidence of linkage of alcohol dependence to a region of chromosome 4p that includes a cluster of 4 genes encoding γ-aminobutyric acid A (GABAA) receptor subunits (Long et al., 1998; Reich et al., 1998). A previous study (Edenberg et al., 2004) found that 31 single nucleotide polymorphisms (SNPs) in GABAA receptor α2 subunit gene (GABRA2), but only 1 of the 20 SNPs in the flanking genes, showed significant association with alcohol dependence. Additional studies have provided the replication of this association in a region of GABRA2 among various ethnic groups (Covault et al., 2004; Fehr et al., 2006; Lappalainen et al., 2005; Soyka et al., 2008); though, there is a negative association study between GABRA2 and alcohol dependence (Matthews et al., 2007). Previous studies have also provided evidence that GABAA receptors mediate several behavioral effects of alcohol such as ethanol self-administration and motor impairment (Davies, 2003; Grobin et al., 1998; Hanchar et al., 2005). GABRA2 gene was associated with the differences in the subjective effects of alcohol including blushing sensations, stimulant and sedative effects (Pierucci-Lagha et al., 2005), and the variance in drinking behavior (Bauer et al., 2007). In the former study (Pierucci-Lagha et al., 2005), the more common A allele of the rs279858 SNP within the GABRA2 gene showed greater subjective effects of alcohol than did individuals with 1 or 2 copies of the alcohol dependence–associated G allele. These findings underscore the potential contributions of variation at GABRA2 to the differences in the subjective responses to alcohol, the variance of drinking behavior, and the risk for alcohol dependence. This study examined the moderating effects of GABRA2 alleles on subjective and physiologic effects of alcohol in healthy social drinkers. We used the alcohol clamp method for alcohol administration, which uses an intravenous infusion of alcohol at rates adjusted online to close the gap between measurements of breath alcohol concentration (BrAC) and the target concentration. The clamp method reduces experimental variance in BrAC (O’Connor et al., 1998) which can be caused by the substantial pharmacokinetic variability following oral alcohol administration. Therefore, the alcohol clamp used in this study is a more exhaustive objective measure than the oral loading of alcohol that was used in the previous study of the effects of GABRA2 on the subjective effects of alcohol assessed only during the ascending limb of the BrAC (Pierucci-Lagha et al., 2005). Our method allowed the evaluation of the initial response to alcohol following the ascending limb of the BrAC as well as the adaptive response to alcohol during the clamped BrAC interval. Based on the previous studies, we hypothesized that GABRA2 alleles would moderate the subjective responses to alcohol measured during not only the ascending limb of BrAC curve but also the clamped BrAC interval. As we expected, subjects with ALDH2*1/*2 showed higher initial response than those with ALDH2*1/*1 (Matsushita et al., manuscript in preparation). Therefore, we divided subjects by ALDH2 genotype and performed further analyses separately in each ALDH2 genotypic group.

Objective: Limited neuronal cell loss is seen in the neuropathology of Wernicke’s encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer’s disease (AD) as a disease control. Methods: CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau181) and amyloid β-protein ending at amino acid 42 (Aβ42) in CSF were also determined for comparison between acute WE with AD. Results: Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau181 and Aβ42 differed between acute WE and AD. Conclusions: Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.