Sleep features in alcohol use disorder: A systematic review and meta-analysis of polysomnographic findings in case-control studies

Background and objectives Alcohol use disorder (AUD) is often linked to sleep problems, but previous studies on sleep abnormalities in AUD have produced inconsistent results. This study aims to provide a comprehensive analysis of objectively measured sleep abnormalities in AUD and determine the impact of related and demographic factors on sleep disturbance. Methods We conducted a comprehensive search of several databases from 1968 to 2023 to identify relevant studies. A total of 12 studies, consisting of 13 datasets, were included in the analysis. We extracted information on sleep microarchitecture, as well as demographic and clinical features, from each study. The GRADE approach was used to assess the reliability and strength of the evidence. Results Patients with AUD exhibited several sleep abnormalities, including longer sleep onset latency, lower sleep efficiency, increased stage 1 sleep, decreased stage 2 sleep, reduced slow wave sleep, and elevated rapid eye movement (REM) sleep density and first REM minute. The sleep patterns in individuals with AUD were also influenced by factors such as ethnicity, age, gender, and abstinence period. Conclusions This study is the largest quantitative assessment of impaired sleep as a diagnostic marker in patients with AUD. Understanding the sleep patterns of individuals with AUD can assist clinicians in developing effective treatment plans for managing sleep-related symptoms associated with AUD. (AU)

The effects of alcohol use on smoking cessation treatment with nicotine replacement therapy: An observational study.

INTRODUCTION: Concurrent users of tobacco and alcohol are at greater risk of harm than use of either substance alone. It remains unclear how concurrent tobacco and alcohol use affects smoking cessation across levels of alcohol use and related problems. This study assessed the relationship between smoking cessation and levels of alcohol use problems. METHODS: 59,018 participants received nicotine replacement therapy through a smoking cessation program. Alcohol use and related symptoms were assessed using the Alcohol Use Disorders Identification Test (AUDIT-10) and the AUDIT-Concise (AUDIT-C). The primary outcome was 7-day point prevalence cigarette abstinence (PPA) at 6-month follow-up. We evaluated the association between alcohol use (and related problems) and smoking cessation using descriptive methods and mixed-effects logistic regression. RESULTS: 7-day PPA at 6-months was lower in groups meeting hazardous alcohol consumption criteria, with the lowest probability of smoking abstinence observed in the highest risk group. The probability of successful tobacco cessation fell with increasing levels of alcohol use and related problems. Adjusted predicted probabilities were 30.3 (95 % CI = 29.4, 31.1) for non-users, 30.2 (95 % CI = 29.4, 31.0) for low-risk users, 29.0 (95 % CI = 28.1, 29.9) for those scoring below 8 on the AUDIT-10, 27.3 (95 % CI = 26.0, 28.6) for those scoring 8-14, and 24.4 (95 % CI = 22.3, 26.5) for those scoring 15 or higher. CONCLUSION: Heavy, hazardous alcohol use is associated with lower odds of successfully quitting smoking compared to low or non-use of alcohol. Targeting alcohol treatment to this group may improve tobacco cessation outcomes.

Reward, relief, and habit drinking profiles in treatment seeking individuals with an AUD.

AIMS: This study aimed to compare reward, relief, and habit treatment-seeking individuals on recent drinking, alcohol use disorder (AUD) phenomenology, and mood. The second aim of the study was to evaluate the predictive validity of reward, relief, and habit profiles. METHOD: Treatment-seeking individuals with an AUD (n = 169) were recruited to participate in a medication trial for AUD (NCT03594435). Reward, relief, and habit drinking groups were assessed using the UCLA Reward Relief Habit Drinking Scale. Group differences at baseline were evaluated using univariate analyses of variance. A subset of participants were enrolled in a 12-week, double-blind, placebo-controlled medication trial (n = 102), and provided longitudinal drinking and phenomenology data. The predictive validity of group membership was assessed using linear regression analyses. RESULTS: At baseline, individuals who drink primarily for relief had higher craving and negative mood than those who drink for reward and habit. Prospectively, membership in the relief drinking group predicted greater alcohol use, greater heavy drinking, and fewer days abstinent compared to those in the reward drinking group. Membership in the relief drinking group also predicted greater alcohol craving, more alcohol-related consequences, and more anxiety symptoms over 12 weeks compared to those in the reward drinking group. CONCLUSIONS: This study provides support for reward and relief drinking motive profiles in treatment-seeking individuals with an AUD. Membership in the relief drinking motive group was predictive of poorer drinking outcomes and more negative symptomology over 12 weeks, indicating that individuals who drink for relief may be a particularly vulnerable sub-population of individuals with AUD.

Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic-Pituitary-Adrenal Axis, and Neurotransmission in Alcohol Use Disorder.

In recent years, there has been a marked increase in interest in the role of the kynurenine pathway (KP) in mechanisms associated with addictive behavior. Numerous reports implicate KP metabolism in influencing the immune system, hypothalamic-pituitary-adrenal (HPA) axis, and neurotransmission, which underlie the behavioral patterns characteristic of addiction. An in-depth analysis of the results of these new studies highlights interesting patterns of relationships, and approaching alcohol use disorder (AUD) from a broader neuroendocrine-immune system perspective may be crucial to better understanding this complex phenomenon. In this review, we provide an up-to-date summary of information indicating the relationship between AUD and the KP, both in terms of changes in the activity of this pathway and modulation of this pathway as a possible pharmacological approach for the treatment of AUD.

Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department.

The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE-4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE-4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence].

Associations between alcohol consumption and empathy in a non-clinical sample: drinking motives as a moderator.

People consume alcohol for multiple reasons. Negative motives are often associated with alcohol-related problems. These problems might be explained by negative effects of high alcohol consumption on empathy. Past studies have associated alcohol use disorder (AUD) with reduced cognitive and affective empathy. Few studies have focused on non-clinical samples and considered behavioral empathy. We examined the links between alcohol consumption and multiple aspects of empathy, and if these links were moderated by negative drinking motives. We collected online data of 520 unselected individuals. All completed the AUD Identification Test (AUDIT) and a Drinking Motives Questionnaire. Affective and cognitive empathy were assessed using the Empathy Quotient. Behavioral empathy was assessed by asking participants how likely they would help the person in each of 24 scenarios involving pain. Helping others in pain was positively predicted by affective and cognitive empathy. Higher AUDIT scores were associated with helping others less, particularly among participants who scored higher on drinking to cope with negative affect. People who drink more and do so to cope with negative affect appear to have less behavioral empathy. This supports the view that negative drinking motives contribute to AUD risk.

Support after return to alcohol use: a mixed-methods study on how abstinence motivation and app use change after return to alcohol use in an app-based aftercare intervention for individuals with alcohol use disorder.

BACKGROUND: As the return to alcohol use in individuals with alcohol use disorder (AUD) is common during treatment and recovery, it is important that abstinence motivation is maintained after such critical incidences. Our study aims to explore how individuals with AUD participating in an app-based intervention with telephone coaching after inpatient treatment perceived their abstinence motivation after the return to alcohol use, whether their app use behavior was affected and to identify helpful factors to maintain abstinence motivation. METHODS: Using a mixed-methods approach, ten participants from the intervention group of the randomized controlled trial SmartAssistEntz who returned to alcohol use and recorded this in the app Appstinence, a smartphone application with telephone coaching designed for individuals with AUD, were interviewed about their experiences. The interviews were recorded, transcribed and coded using qualitative content analysis. App use behavior was additionally examined by using log data. RESULTS: Of the ten interviewees, seven reported their abstinence motivation increased after the return to alcohol use. Reasons included the reminder of negative consequences of drinking, the desire to regain control of their situation as well as the perceived support provided by the app. App data showed that app use remained stable after the return to alcohol use with an average of 58.70 days of active app use (SD = 25.96, Mdn = 58.50, range = 24-96, IQR = 44.25) after the return to alcohol use which was also indicated by the participants' reported use behavior. CONCLUSIONS: The findings of the study tentatively suggest that the app can provide support to individuals after the return to alcohol use to maintain and increase motivation after the incidence. Future research should (1) focus on specifically enhancing identification of high risk situations and reach during such critical incidences, (2) actively integrate the experience of the return to alcohol use into app-based interventions to better support individuals in achieving their personal AUD behavior change goals, and (3) investigate what type of support individuals might need who drop out of the study and intervention and discontinue app use altogether. TRIAL REGISTRATION: The primary evaluation study is registered in the German Clinical Trials Register (DRKS, registration number DRKS00017700) and received approval of the ethical committee of the Friedrich-Alexander University Erlangen-Nuremberg (193_19 B).

Determinants of depressive and alcohol use disorders among female sex workers in Ethiopia: evidence from a national bio-behavioral survey, 2020.

BACKGROUND: Female sex workers (FSWs) face an elevated risk of developing mental health disorders and alcohol use disorders (AUD), which in turn increase their vulnerability to HIV and other sexually transmitted infections (STIs) and other negative outcomes. To effectively address both of these health issues, it is crucial to understand the shared key determinants underlying these illnesses, which is a substantial knowledge gap in Ethiopia and elsewhere in the world. Therefore, this study aimed to identify the common key determinants of depression and AUD among FSWs in Ethiopia using a bivariate multivariable ordinal logistic model. METHODS: We analyzed cross-sectional biobehavioral data collected in 2020 from 16 cities and major towns in Ethiopia using the respondent-driven sampling (RDS) technique, which involved a total of 6,085 FSWs. FSWs who had lived at the study sites for at least a month before the study period were deemed eligible for recruitment. Major depressive disorder (DD) and AUD were screened using the Patient Health Questionnaire (PHQ9) and alcohol use disorder identification test (AUDIT), respectively. We used descriptive statistics to summarize study population characteristics and bivariate multivariable ordinal logistic regression (BMOLR) to identify common determinants of DD and AUD combined and their nonnormal correlation. RESULTS: Among 6085 FSWs screened for DD and AUD, 13.5% and 4.0% have met the criteria for moderate and severe depressive disorder, respectively, and 20.3% and 34.7% have met the AUDIT criteria for harmful or hazardous behavior and alcohol dependence, respectively. FSW with experience of inconsistent condom use, condom failure, violence, mobility, use of any drugs, non-paying partners, abortion, and selling sex for more than five years were associated with an increase in the severity of both disorders. A high average income from selling sex and the number of paying partners reduced the severity of depression and increased the level of alcohol dependence. Being HIV positive and ever having anal sex were associated only with an increase in depression. CONCLUSION: Major DD and AUD are prevalent among FSWs in Ethiopia. The findings revealed that common key determinants, which exacerbated the severity of both disorders, were also risk factors for HIV and other STIs. Consequently, integrated STI strategies are essential in the screening, referral, and treatment of depression and AUD. Intervention packages should encompass determinants of depression and AUD, including condom utilization, drug use, mobility between towns, abortion, violence, and counseling services. Additionally, strategies to ensure economic security should be incorporated.

Alcohol Use Disorder and Chronic Pain: An Overlooked Epidemic.

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which may escalate into AUD. This narrative review discusses the intricate relationship between AUD and chronic pain. Based on the literature available, the authors present a theoretical model explaining the reciprocal relationship between AUD and chronic pain across alcohol intoxication and withdrawal. They propose that the use of alcohol for analgesia rapidly gives way to acute tolerance, triggering the need for higher levels of alcohol consumption. Attempts at abstinence lead to alcohol withdrawal syndrome and hyperalgesia, increasing the risk of relapse. Chronic neurobiological changes lead to preoccupation with pain and cravings for alcohol, further entrenching both conditions. To stimulate research in this area, the authors review methodologies to improve the assessment of pain in AUD studies, including self-report and psychophysical methods. Further, they discuss pharmacotherapies and psychotherapies that may target both conditions, potentially improving both AUD and chronic pain outcomes simultaneously. Finally, the authors emphasize the need to manage both conditions concurrently, and encourage both the scientific community and clinicians to ensure that these intertwined conditions are not overlooked given their clinical significance.

Associations Between a Primary Care-Delivered Alcohol-Related Brief Intervention and Subsequent Opioid-Related Outcomes.

OBJECTIVE: The co-occurrence of unhealthy alcohol use and opioid misuse is high and associated with increased rates of overdose, emergency health care utilization, and death. The current study examined whether receipt of an alcohol-related brief intervention is associated with reduced risk of negative downstream opioid-related outcomes. METHODS: This retrospective cohort study included all VISN-6 Veterans Affairs (VA) patients with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening results (N=492,748) from 2014 to 2019. Logistic regression was used to examine the association between documentation of an alcohol-related brief intervention and probability of a new 1) opioid prescription, 2) opioid use disorder (OUD) diagnosis, or 3) opioid-related hospitalization in the following year, controlling for demographic and clinical covariates. RESULTS: Of the veterans, 13% (N=63,804) had "positive" AUDIT-C screen results. Of those, 72% (N=46,216) had a documented alcohol-related brief intervention. Within 1 year, 8.5% (N=5,430) had a new opioid prescription, 1.1% (N=698) had a new OUD diagnosis, and 0.8% (N=499) had a new opioid-related hospitalization. In adjusted models, veterans with positive AUDIT-C screen results who did not receive an alcohol-related brief intervention had higher odds of new opioid prescriptions (adjusted odds ratio [OR]=1.10, 95% CI=1.03-1.17) and new OUD diagnoses (adjusted OR=1.19, 95% CI=1.02-1.40), while new opioid-related hospitalizations (adjusted OR=1.19, 95% CI=0.99-1.44) were higher although not statistically significant. Removal of medications for OUD (MOUD) did not impact associations. All outcomes were significantly associated with an alcohol-related brief intervention in unadjusted models. CONCLUSIONS: The VA's standard alcohol-related brief intervention is associated with subsequent lower odds of a new opioid prescription or a new OUD diagnosis. Results suggest a reduction in a cascade of new opioid-related outcomes from prescriptions through hospitalizations.

Neural Correlates of Stress and Alcohol Cue-Induced Alcohol Craving and of Future Heavy Drinking: Evidence of Sex Differences.

OBJECTIVE: Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue-induced craving compared with neutral cue-induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences. METHODS: Treatment-seeking adults with AUD (N=77; 46 men and 31 women) completed a functional MRI task involving stress, alcohol, and neutral cue exposure with repeated assessments of alcohol craving. Most of these participants (N=72; 43 men and 29 women) then participated in an 8-week standardized behavioral AUD treatment program, during which the percentage of heavy drinking days was assessed. RESULTS: Significant increases in both stress and alcohol cue-induced craving relative to neutral cue-induced craving were observed, with a greater alcohol-neutral contrast in craving relative to the stress-neutral contrast among men and equivalent stress-neutral and alcohol-neutral contrasts in craving among women. Whole-brain voxel-based regression analyses showed craving-associated hyperactivation in the neutral condition, but hypoactive prefrontal (ventromedial and lateral prefrontal, supplementary motor, and anterior cingulate regions) and striatal responses during exposure to stressful images (stress-neutral contrast) and alcohol cues (alcohol-neutral contrast), with significant sex differences. Additionally, a higher percentage of heavy drinking days was associated with hypoactivation of the subgenual anterior cingulate cortex and the bed nucleus of the stria terminalis in the stress-neutral contrast among women, hyperactivation of the hypothalamus in the stress-neutral contrast among men, and hyperactivation of the hippocampus in the alcohol-neutral contrast among men. CONCLUSIONS: Sex differences in stress- and alcohol cue-induced responses in the cortico-striatal-limbic network related to subjective alcohol craving and to heavy drinking indicated that distinct brain circuits underlie alcohol use outcomes in women and men. These findings underscore the need for sex-specific therapeutics to address this neural dysfunction effectively.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Liver cirrhosis in a patient with alcohol dependence and autoimmune hepatitis.

BACKGROUND: Liver cirrhosis is the end-stage entity for a wide variety of chronic liver pathologies. These include viral hepatitis B and C, alcoholic liver disease, non-alcoholic fatty liver disease, hemochromatosis, Wilson disease, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis. In the majority of cases, liver cirrhosis remains completely asymptomatic until acute decompensation occurs. Patients may present complications of portal hypertension such as gastro-esophageal varices and upper digestive hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepato-renal syndrome. Establishing the right etiology of cirrhosis is of paramount importance as it helps the treating physician plan the best suitable treatment options and also improves overall outcome. CASE REPORT: We present a case of a chronic alcohol consumer, which, over time, resulted in alcoholic cirrhosis. Initial diagnosis comprised of alcoholic liver disease. However, a further look into the medical history of the patients indicated the presence of underlying autoimmune liver disease, such as autoimmune hepatitis, which might have also contributed to the chronic liver injury. CONCLUSIONS: Multiple factors can lead to liver cirrhosis. Although the most commonly found entity is alcoholism, it cannot be taken as a thumb rule for the only possible etiology. In-depth analysis and proper differential diagnosis should be carefully conducted in order not to miss out on other possible causes. As seen in our case, where an underlying autoimmune hepatitis was found to be the culprit, but due to a long history of alcohol consumption, it was masked at first instance.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Patterns and Factors Associated With Alcohol Misuse Among Young Black Men Who Have Sex With Men in New York City.

Alcohol misuse is a significant health concern among gay, bisexual, same-gender-loving, and other men who have sex with men (MSM). Yet, little is known about the severity and predictors of alcohol misuse among self-reported young Black MSM. This study aimed to identify patterns of and factors associated with alcohol misuse in a sample of young Black MSM living in New York City. Baseline data from a randomized controlled trial aimed at improving the uptake of HIV testing among 250 MSM aged 18 to 29 were analyzed. Log-binominal regression analyses were conducted to assess the association of demographic and psychosocial factors with alcohol misuse in the past year and past 3 months among young Black MSM. Overall, 33.2% and 28.0% of young Black MSM in the study experienced alcohol misuse in the past year and past 3 months, respectively. In the adjusted model, factors positively associated with past-year alcohol misuse included marijuana use, a history of drug use, and having one-two or more than two male sex partners. Likewise, participants who used marijuana and those with one-two or more than two male partners were more likely to report past 3-month alcohol misuse. No significant association was found between positive screening for depressive symptoms, chemsex, internalized homophobia, and the likelihood of having alcohol misuse. The high prevalence of alcohol misuse underscores the importance of raising awareness of alcohol misuse and designing alcohol risk reduction programs that jointly address HIV risk among young Black MSM.

ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of the Acute Antisuicidal and Antidepressant Effects of Intranasal (R,S)-Ketamine in Severe Unipolar and Bipolar Depression With and Without Comorbid Alcohol Use Disorder.

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic (R,S)-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients.Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN (R,S)-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure.Results: No significant group × time effect was noted for SI (F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression (F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD (r =0.927, P = .023) that was absent in patients with AUD (r = 0.39, P = .44).Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted.Trial Registration: ClinicalTrials.gov identifier: NCT03539887.

Prevalence of alcohol and other psychoactive substance abuse and association with depression among medical students in Niger Delta University, Bayelsa State.

Introduction: alcohol and other psychoactive substances have adverse health effects, particularly on young people. This study determined the prevalence of alcohol and other psychoactive substance abuse and its association with depression among Niger Delta University, Bayelsa State, Nigeria, medical students. Methods: a cross-sectional study involving 243 medical students who completed a patient-rated version of the Mini International Neuropsychiatric Interview (MINI-PR). For analyzing the data, descriptive and inferential statistics were employed. Results: most respondents were 18 to 24 years old (67.1%), and 52.7% were male; the prevalence of major depressive episodes (current) and lifetime alcohol and other psychoactive use was 30.5%, 25.5%, and 21%, respectively. Also, the prevalence of current alcohol abuse and dependence was 5.8% and 4.9%, respectively. Alcohol use (χ2: 12.57, p = 0.001) and abuse (χ2: 22.33, p = 0.001) were significantly associated with depression. Psychoactive substance use was significantly associated with depression (χ2: 12.91, p = 0.001). The odds of having depression increased with the use of alcohol (OR: 3.54; 95% CI: 1.71-7.33) and psychoactive substances (OR: 4.52; 95% CI: 1.88-10.88). Conclusion: alcohol and psychoactive substance use were significantly associated with depression. Organizing interventions to reduce such unhealthy social practices among medical students is necessary.