A smartphone app-based intervention combined with face-to-face sessions for alcohol dependence at internal medicine clinics: A randomized controlled trial.

BACKGROUND: Addressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be "prescribed" for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002. METHODS: In a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed. RESULTS: We enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of -6.99 days (95% CI: -12.4 to -1.6 days, standardized mean difference: -0.80). CONCLUSIONS: These results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002.

National burden of gambling in Japan: an estimation from an online-based cross-sectional investigation and national epidemiological survey.

BACKGROUND: Gambling is a popular leisure activity in many countries, often expected to boost regional economies. Nevertheless, its negative impacts remain a significant concern. Gambling disorder is recognized as the most severe consequence; however, even non- or low-risk gamblers may also face negative impacts. This study aimed to estimate the number of Japanese gamblers experiencing gambling-related harm (GRH) and its distribution across six life domains, financial, relational, emotional, health, social and other aspects, based on the severity of their problem gambling risk. METHODS: This cross-sectional study relied on an online survey conducted between August 5 and 11, 2020. Participants aged 20 years and above, who engaged in gambling during 2019 were recruited via a market research company. The survey assessed the prevalence of GRH 72 items among four gambler risk groups (non-problem, low-, moderate-, and high-risk), as categorized by the Problem Gambling Severity Index. The data was adjusted for population weighting using representative national survey data: the 2017 Comprehensive Survey of Living Conditions and the 2017 Epidemiological Survey on Gambling Addictions. RESULTS: Out of the 28,016 individuals invited to the survey, 6,124 participated in the screening, 3,113 in the main survey, and 3,063 provided valid responses. After adjusting the survey data, it was estimated that 39.0 million (30.8%) of Japan's 126.8 million citizens gambled in 2019. Among them, 4.44 million (11.4%) experienced financial harm, 2.70 million (6.9%) health harm, 2.54 million (6.5%) emotional harm, 1.31 million (3.4%) work/study harm, 1.28 million (3.3%) relationship harm, and 0.46 million (1.2%) other harm. Although high-risk gamblers experienced severe harm at the individual level, over 60% of gamblers who experienced GRHs were non- and low-risk gamblers, with the exception of other harm, at the population level. CONCLUSIONS: The study highlighted the prevention paradox of gambling in Japan. While national gambling policies primarily focus on the prevention and intervention for high-risk gamblers, a more effective approach would involve minimizing GRH across the entire population.

Prevalence of hazardous drinking and suspected alcohol dependence in Japanese primary care settings.

OBJECTIVE: We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns. METHODS: From July to August 2023, we conducted a multi-site cross-sectional study as a screening survey for participants in a cluster randomized controlled trial. The trial included outpatients aged 20-74 from primary care clinics. Using the Alcohol Use Disorders Identification Test (AUDIT) alongside a self-administered questionnaire, we evaluated the prevalence of hazardous drinking and suspected alcohol dependence, patients' readiness to change, and their awareness of others' concerns. RESULTS: Among the 1388 participants from 18 clinics, 22% (95% confidence interval (CI): 20% to 24%) were identified as engaging in hazardous drinking or suspected of being alcohol dependent. As the AUDIT scores increased, so did their readiness to change. However, only 22% (95%CI: 16% to 28%) of those with scores ranging from 8 to 14 reported that others, including physicians, had expressed concerns about their drinking during the past year. For those with scores of 15 or higher, the figure was 74%. CONCLUSIONS: This study underscores the need for universal or high-risk alcohol screening and brief intervention in Japanese primary care settings. Trial registry UMIN-CTR (https://www.umin.ac.jp/ctr/) (UMIN000051388).

Associations of ADH1B and ALDH2 genotypes and alcohol flushing with drinking history, withdrawal symptoms, and ICD-10 criteria in Japanese alcohol-dependent men.

OBJECTIVES: Given the high prevalence of fast-metabolizing alcohol dehydrogenase-1B*2 (ADH1B*2 ) and inactive aldehyde dehydrogenase-2*2 (ALDH2*2 ) alleles in East Asians, we evaluated how the ADH1B / ALDH2 genotypes and alcohol flushing might affect the development of alcohol dependence (AD). METHODS: We evaluated how the ADH1B / ALDH2 genotypes and self-reported alcohol flushing affected history of drinking events and withdrawal symptoms and ICD-10 criteria in 4116 Japanese AD men. RESULTS: The ADH1B*1/*1 group and ALDH2*1/*1 group were 1-5 years younger than the ADH1B*2 (+) and ALDH2*1/*2 groups, respectively, for all of the ages at onset of habitual drinking, blackouts, daytime drinking, uncontrolled drinking, withdrawal symptoms, and first treatment for AD, and the current age. Blackouts were more common in the ADH1B*1/*1 group and ALDH2*1/*1 group. Daytime drinking, uncontrolled drinking, and withdrawal symptoms, such as hand tremor, sweating, convulsions, and delirium tremens/hallucinations were more common in the ADH1B*1/*1 group. The ADH1B*1/*1 was positively associated with the ICD-10 criteria for 'tolerance' and 'withdrawal symptoms'. The ADH1B*1/*1 group and ALDH2*1/*2 group had a larger ICD-10 score. Never flushing was reported by 91.7% and 35.2% of the ALDH2*1/*1 and ALDH2*1/*2 carriers, respectively. After a 1-2-year delay in the onset of habitual drinking in the former-/current-flushing group, no differences in the ages of the aforementioned drinking milestones were found according to the flushing status. CONCLUSION: The ADH1B*1/*1 and ALDH2*1/*1 accelerated the development of drinking events and withdrawal symptoms in Japanese AD patients. ICD-10 score was larger in the ADH1B*1/*1 group and ALDH2*1/*2 group. The effects of alcohol flushing on drinking events were limited.

Acetaldehyde-mediated increase in glutamatergic and N-acetylaspartate neurometabolite levels in the midcingulate cortex of ALDH2*1/*2 heterozygous young adults.

BACKGROUND: To elucidate the neurobiology underlying alcohol's effect on the human brain, we examined the acute effects of moderate alcohol administration on levels of glutamatergic neurometabolites and N-acetylaspartate, an amino acid found in neurons, may reflect disordered neuronal integrity. METHODS: Eighteen healthy Japanese participants (7 males/11 females) aged 20-30 years who were heterozygous for an inactive allele of acetaldehyde dehydrogenase-2 (ALDH/*1/*2) were included. Participants underwent an intravenous alcohol infusion using the clamp method at a target blood alcohol concentration (BAC) of 0.50 mg/mL for 90 min within a range of ±0.05 mg/mL. We examined glutamate + glutamine (Glx) and N-acetylaspartate N-acetylaspartylglutamate (NAA) levels in the midcingulate cortex (MCC) using 3 T 1 H-MRS PRESS at baseline, 90 min, and 180 min (i.e., 90 min after alcohol infusion was finished). A two-way repeated-measures analysis of variance was used to assess longitudinal changes in Glx and NAA levels, with time and sex as within- and between-subject factors, respectively. Pearson's correlation coefficients were calculated among neurometabolite levels and BAC or blood acetaldehyde concentration (BAAC). RESULTS: Both Glx (F(2,32) = 8.15, p = 0.004, η2 = 0.15) and NAA (F(2,32) = 5.01, p = 0.04, η2 = 0.07) levels were increased after alcohol injection. There were no sex or time × sex interaction effects observed. NAA levels were positively correlated with BAAC at 90 min (r(13) = 0.77, p = 0.01). There were no associations between neurometabolite levels and BAC. CONCLUSIONS: Both Glx and NAA levels in the MCC increased in response to the administration of moderate concentrations of alcohol. Given positive associations between NAA levels and BAAC and the hypothetical glutamate release via dopamine pathways, the effects of drinking on the MCC in the acute phase may be ascribed to acetaldehyde metabolized from alcohol.

New-onset addictions in patients with alcohol dependence: A cross-sectional study.

BACKGROUND: Individuals who are addicted to one addiction are at an increased risk for developing another new addiction. New-onset addictions among patients with alcohol dependence needs to be considered for more effective treatment of alcohol dependence. METHODS: In this cross-sectional study, Japanese outpatients with alcohol dependence were assessed using a comprehensive, originally designed questionnaire to determine whether they were addicted to substances or behaviors other than alcohol. The prevalence rates of new-onset addictions were compared between alcohol-dependent patients who had abstained from alcohol for a year or more and those who had not. Multiple regression analysis was performed to examine the association between the number of new-onset addictions and the demographic and clinical characteristics. RESULTS: One hundred and nine outpatients with alcohol dependence (54.6±11.0 years; 97 men) participated in the study. The prevalence of new-onset addictions was 41.3%. No significant differences were found in the prevalence of new-onset addictions between the patients who had abstained for a year or more and those who had not. Multiple regression analysis revealed that the number of new-onset addictions was positively associated with the presence of psychiatric comorbidity (ß = 0.24; p = 0.02) and use of benzodiazepines (ß = 0.20; p = 0.04) with a R2 of 0.153. CONCLUSION: Alcohol dependent patients with characteristics such as psychiatric comorbidity and use of benzodiazepines should be given more attention to the development of new-onset addictive behaviors. On the other hand, those behaviors could be acceptable for harm-reduction unless excessive and loss of control.

Impact of COVID-19 and restricted self-help group attendance on drinking behavior among people with alcohol use disorder: Results of a nationwide cross-sectional survey.

BACKGROUND: Concerns regarding symptom severity and the risk of relapse among people seeking recovery from alcohol use disorder (AUD) have been raised since the onset of the COVID-19 pandemic. Owing to preventive measures implemented during the pandemic (social distancing or lockdown), self-help group (SHG) meetings were restricted. However, the impact of deprivation of onsite recovery meetings on drinking behavior and risk among SHG members with AUD remains unclear. We examined the proportion of SHG members who reported drinking and their reasons for drinking during the early stages of the pandemic and the effect of nonattendance at onsite recovery meetings on drinking behavior during the early pandemic period, stratified by gender. METHODS: A national cross-sectional survey of Japanese SHG members was conducted to measure self-reported alcohol consumption, sociodemographic characteristics, AUD diagnosis, treatment status, SHG meeting attendance, membership duration, psychological distress, and health-related variables. Of 6478 SHG members, 2955 (male: n = 2678; female: n = 277; response rate: 46.7%) responded, and the responses were analyzed using a gender-stratified multivariate logistic regression model. RESULTS: Most participants reported having abstained from alcohol use, while 6% of the respondents reported having consumed alcohol during the early stages of the pandemic. The proportion of "drinkers" among women (10.5%) was significantly higher than that among men (5.9%; p = 0.012). Through multivariate model analysis, the factors associated with drinking during the pandemic were identified as psychological distress (among men and women) and not attending onsite recovery meetings (among men). Conversely, a longer duration of SHG membership was associated with less drinking during the pandemic for both genders. CONCLUSIONS: Most SHG members appear to have remained abstinent during the early stages of the COVID-19 pandemic. However, psychological distress in both genders and the inability to attend recovery meetings among men may have influenced drinking behavior.

Highly endorsed screening and assessment scales for alcohol problems: A systematic review.

BACKGROUND: Problems associated with alcohol use are multidimensional with psychiatric, psychological, physical, and social aspects, which makes it challenging to choose appropriate assessment scales. However, there has been no systematic evaluation of existing alcohol scales. METHODS: A systematic literature search was conducted for articles that assessed the psychometric properties of scales for alcohol use disorder on March 19, 2023, using Medline, EMBASE, and PsycINFO. Only scales whose original development papers were cited more than 20 times were included. The methodological quality and psychometric properties of the scales were evaluated using COnsensus-based Standards for the selection of health Measurement INstruments. The overall rating of the scales were assessed with a score ranging from 0 to 18. RESULTS: In total, 314 studies and 40 scales were identified. These scales differ widely in measurement methods, target populations, and psychometric properties. The overall mean score was 6.3, and only the following three scales received >9 points suggesting a moderate level of evidence: Alcohol Use Disorders Identification Test (AUDIT), Alcohol Dependence Scale (ADS), and Short Alcohol Dependence Data Questionnaire (SADD). Measurement error and responsiveness were not evaluated or reported in the included scales. CONCLUSIONS: Although the AUDIT, ADS, and SADD were rated the highest among the 40 scales, they showed, at most, a moderate level of evidence. These findings underscore the need to accumulate further evidence to assure the quality of the scales. It may be advisable to select and combine scales to meet the purpose of the assessment.

[Pharmacological Treatment for Alcohol Dependence].

This review provides an overview of medications for the treatment of alcohol dependence. The medications were classified into three categories: medications for alcohol withdrawal, medications for maintaining abstinence from alcohol or reducing its consumption, and medications for insomnia in patients with alcohol dependence. Acamprosate is the first choice in maintaining abstinence, whereas to reduce drinking, nalmefene, which is available in Japan, is used. However, medications are not "stand-alone" treatments for alcohol dependence. Pharmacological treatments for maintaining abstinence and reducing drinking are effective only when used in conjunction with psychosocial treatment, such as cognitive and behavioral therapy for alcohol dependence.

Wearable Sensor and Mobile App-Based mHealth Approach for Investigating Substance Use and Related Factors in Daily Life: Protocol for an Ecological Momentary Assessment Study.

BACKGROUND: Digital health technologies using mobile apps and wearable devices are a promising approach to the investigation of substance use in the real world and for the analysis of predictive factors or harms from substance use. Moreover, consecutive repeated data collection enables the development of predictive algorithms for substance use by machine learning methods. OBJECTIVE: We developed a new self-monitoring mobile app to record daily substance use, triggers, and cravings. Additionally, a wearable activity tracker (Fitbit) was used to collect objective biological and behavioral data before, during, and after substance use. This study aims to describe a model using machine learning methods to determine substance use. METHODS: This study is an ongoing observational study using a Fitbit and a self-monitoring app. Participants of this study were people with health risks due to alcohol or methamphetamine use. They were required to record their daily substance use and related factors on the self-monitoring app and to always wear a Fitbit for 8 weeks, which collected the following data: (1) heart rate per minute, (2) sleep duration per day, (3) sleep stages per day, (4) the number of steps per day, and (5) the amount of physical activity per day. Fitbit data will first be visualized for data analysis to confirm typical Fitbit data patterns for individual users. Next, machine learning and statistical analysis methods will be performed to create a detection model for substance use based on the combined Fitbit and self-monitoring data. The model will be tested based on 5-fold cross-validation, and further preprocessing and machine learning methods will be conducted based on the preliminary results. The usability and feasibility of this approach will also be evaluated. RESULTS: Enrollment for the trial began in September 2020, and the data collection finished in April 2021. In total, 13 people with methamphetamine use disorder and 36 with alcohol problems participated in this study. The severity of methamphetamine or alcohol use disorder assessed by the Drug Abuse Screening Test-10 or the Alcohol Use Disorders Identification Test-10 was moderate to severe. The anticipated results of this study include understanding the physiological and behavioral data before, during, and after alcohol or methamphetamine use and identifying individual patterns of behavior. CONCLUSIONS: Real-time data on daily life among people with substance use problems were collected in this study. This new approach to data collection might be helpful because of its high confidentiality and convenience. The findings of this study will provide data to support the development of interventions to reduce alcohol and methamphetamine use and associated negative consequences. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44275.

Nonsmoking after simultaneous alcohol abstinence and smoking cessation program was associated with better drinking status outcome in Japanese alcohol-dependent men: A prospective follow-up study.

BACKGROUND: Growing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians. METHOD: We prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation. RESULTS: Nonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge. CONCLUSION: Nonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs.

Accelerated cognitive decline after the COVID-19 pandemic in a community population of older persons with cognitive impairment: A 4-year time series analysis in the Tokyo Metropolis area.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has led to lifestyle restrictions and might be associated with long-term changes in cognitive function. The aim of the present study was to elucidate the overall effect of the COVID-19 pandemic on the cognitive trajectory of a cohort of patients with cognitive impairment. METHODS: We enrolled 160 patients who had been making regular visits to a medical center for dementia. Cognitive function was assessed based on changes in scores on the Mini-Mental State Examination before and during the COVID-19 pandemic throughout a 4-year period. The trajectory of cognitive decline was determined by carrying out a time series analysis using a state-space model. RESULTS: Crude analysis showed that the Mini-Mental State Examination scores decreased from 20.9 ± 4.4 points (mean ± SD) at the time of the initial cognitive assessments to 17.5 ± 5.6 points at the time of the final assessments, and the decline rate was 1.15 ± 1.78 points per year (P < 0.0001). The time series analysis showed an accelerated cognitive trajectory after the COVID-19 outbreak, and the average decline in the Mini-Mental State Examination scores was 0.46 points (95% confidence interval 0.034-0.91) per year before the COVID-19 pandemic, and a steeper decline of 1.87 points (95% confidence interval 1.34-2.67) per year after the outbreak. CONCLUSIONS: The COVID-19 pandemic accelerated the rate of cognitive decline in patients with cognitive impairment fourfold in comparison with before the pandemic. Specific strategies designed for cognitively older people in the "new normal" will reconcile both requirements, reducing the risk of infection, and maintaining their physical and psychological well-being. Geriatr Gerontol Int 2023; 23: 200-204.

Influence of ADHD, especially attention-deficit characteristics, on the course of alcohol-dependent individuals.

BACKGROUND: While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined. METHODS: This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated. RESULTS: The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of "Recurrence" and lower rates of "Abstinence" and "Controlled drinking" (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003). CONCLUSION: ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.

Patterns of functional connectivity alterations induced by alcohol reflect somatostatin interneuron expression in the human cerebral cortex.

Acute alcohol administration affects functional connectivity, yet the underlying mechanism is unknown. Previous work suggested that a moderate dose of alcohol reduces the activity of gamma-aminobutyric acidergic (GABAergic) interneurons, thereby leading to a state of pyramidal disinhibition and hyperexcitability. The present study aims to relate alcohol-induced changes in functional connectivity to regional genetic markers of GABAergic interneurons. Healthy young adults (N = 15, 5 males) underwent resting state functional MRI scanning prior to alcohol administration, immediately and 90 min after alcohol administration. Functional connectivity density mapping was performed to quantify alcohol-induced changes in resting brain activity between conditions. Patterns of differences between conditions were related to regional genetic markers that express the primary GABAergic cortical interneuron subtypes (parvalbumin, somatostatin, and 5-hydroxytryptamine receptor 3A) obtained from the Allen Human Brain Atlas. Acute alcohol administration increased local functional connectivity density within the visual cortex, sensorimotor cortex, thalamus, striatum, and cerebellum. Patterns of alcohol-induced changes in local functional connectivity density inversely correlated with somatostatin cortical gene expression. These findings suggest that somatostatin-expressing interneurons modulate alcohol-induced changes in functional connectivity in healthy individuals.

Influence of alcohol and acetaldehyde on cognitive function: findings from an alcohol clamp study in healthy young adults.

AIMS: To investigate the acute effects of intravenous alcohol and its metabolite acetaldehyde on cognitive function in healthy individuals. DESIGN: Experimental pre-test/post-test design. SETTING: Kurihama Medical and Addiction Center, Japan. PARTICIPANTS: A total of 298 healthy Japanese people age 20 to 24 years. MEASUREMENTS: Participants underwent an intravenous alcohol infusion with a target blood alcohol concentration (BAC) of 0.50 mg/mL for 180 minutes. Participants completed the continuous performance test (CPT) for sustained attention, the paced auditory serial addition test (PASAT) for working memory, and the reaction time test (RTT) for speed/accuracy, along with the blood test for BAC and blood acetaldehyde concentration (BAAC) at baseline, 60 and 180 minutes. FINDINGS: Although the target BAC was maintained during the infusion, BAAC peaked at 30 minutes and then gradually declined (η2 = 0.18, P < 0.01). The CPT scores worsened, and the changes between 0 and 60 minutes were correlated with BAAC (correct detection, η2 = 0.09, P < 0.01; r = -0.34, P < 0.01; omission errors, η2 = 0.08, P < 0.01; r = 0.34, P < 0.01). PASAT scores improved through 180 minutes, whereas the changes between 0 and 60 minutes were negatively correlated with BAAC (task one, η2 = 0.02, P < 0.01; r = -0.25, P < 0.01; task two, η2 = 0.03, P < 0.01; r = -0.28, P < 0.01). Although RTTs worsened, they were not associated with BAC or BAAC. None of these comparisons maintained the time effect after controlling for body height. CONCLUSIONS: Acetaldehyde exposure following acute intravenous alcohol appears to have a negative impact on sustained attention and working memory, whereas there seems to be only a minor effect of moderate alcohol concentration on speed and accuracy.

Alcohol dependence severity determines the course of treatment-seeking patients.

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 < 0.001, respectively) than those with poorer drinking outcomes. CONCLUSIONS: The present study showed that more severe alcohol dependence predicts a poorer course after alcohol treatment, as reflected by findings on multiple measures. These results suggest that assessing the dependence severity at the outset of treatment could be useful both in predicting treatment outcome and targeting interventions to alcohol-dependent individuals who need additional support in their recovery.

Combinations of alcohol-induced flushing with genetic polymorphisms of alcohol and aldehyde dehydrogenases and the risk of alcohol dependence in Japanese men and women.

OBJECTIVE: The risk of alcohol dependence (AD) in Japanese men and women was evaluated according to combinations of alcohol flushing and aldehyde dehydrogenase-2 (ALDH2, rs671) and alcohol dehydrogenase-1B (ADH1B, rs1229984) genotypes, all of which are known to determine AD susceptibility in Asians. Previous studies have focused on men, since women account for a smaller proportion of AD subjects. METHODS: Case control studies were conducted between 3721 male and 335 female AD Japanese and 610 male and 406 female controls who were asked about their current or former tendency to experience facial flushing after drinking a glass of beer and underwent ALDH2 and ADH1B genotyping. The time at which alcohol-induced facial flushing tendencies had disappeared in former-flushing AD subjects was also evaluated. RESULTS: Current alcohol flushing, the inactive ALDH2*1/*2 genotype, and the fast-metabolizing ADH1B*2 allele were less frequently found in the AD groups. Although alcohol flushing was strongly influenced by the ALDH2 and ADH1B genotypes, multiple logistic model showed that never or former flushing and the genotype combinations were independent strong risk factors of AD in men and women. Never or former flushing (vs. current flushing) markedly increased the odds ratios of AD in carriers of each of the ALDH2 and ADH1B genotype combinations. The temporal profiles for drinking and flushing in former-flushing AD subjects revealed that the flushing response disappeared soon after or before the start of habitual drinking during young adulthood, regardless of the ALDH2 genotype. CONCLUSION: Although alcohol flushing is influenced by the ALDH2 and ADH1B genotypes, constitutional or acquired flushing tolerance is an independent susceptibility trait for AD. The combination of the alcohol flushing status and the ALDH2 and ADH1B genotypes can provide a better new strategy for AD risk assessment than the alcohol flushing status alone or the genotypes alone in Asian men and women.

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 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.