Association of Alcohol Use with COVID-19 Infection and Hospitalization Among People Living with HIV in the United States, 2020.

Alcohol use was associated with elevated COVID-19 risk in the general population. People with HIV (PWH) have high prevalences of alcohol use. To evaluate the effect of alcohol use on COVID-19 risks among PWH, we estimated the risk of COVID-19 diagnosis and COVID-19-related hospitalization among PWH in routine care at 8 HIV primary care centers that contributed data to the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort according to their alcohol use just prior to the COVID-19 pandemic. The CNICS data repository includes demographic characteristics, clinical diagnoses, and laboratory test results from electronic medical records and other sources. Alcohol use, substance use, and mental health symptoms were self-reported on tablet-based standardized surveys. Alcohol use was categorized according to standard, sex-specific Alcohol Use Disorder Identification Test-Consumption instrument cut-offs. We followed 5,496 PWH (79% male, 48% Black race, median age = 53 years) from March 1, 2020 to December 31, 2020. Relative to PWH with no baseline alcohol use, the adjusted hazard ratio (aHR) of COVID-19 diagnosis was 1.09 (95% confidence interval [CI]: 0.78, 1.51) for lower-risk drinking and 1.19 (95%CI: 0.81, 1.73) for unhealthy drinking. The aHR of COVID-19-related hospitalization was 0.82 (95%CI: 0.33, 1.99) for lower-risk drinking and 1.25 (95%CI: 0.50, 3.09) for unhealthy drinking. Results were not modified by recent cocaine or non-prescribed opioid use, depressive symptoms, or diagnoses of alcohol use disorder. The study suggested a slightly increased, but not statistically significant risk of COVID-19 diagnosis and hospitalization associated with unhealthy alcohol use.

Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Alcohol Use Disorder and Recent Alcohol Use and HIV Viral Non-Suppression Among People Engaged in HIV Care in an Urban Clinic, 2014-2018.

We estimated joint associations between having history of alcohol use disorder (AUD) (based on prior ICD-9/ICD-10 codes) and recent self-reported alcohol use and viral non-suppression (≥ 1 viral load measurement > 20 copies/mL in the same calendar year as alcohol consumption was reported) among patients on ART enrolled in routine care, 2014-2018, in an urban specialty clinic. Among 1690 patients, 26% had an AUD, 21% reported high-risk alcohol use, and 39% had viral non-suppression. Relative to person-years in which people without AUD reported not drinking, prevalence of viral non-suppression was higher in person-years when people with AUD reported drinking at any level; prevalence of viral non-suppression was not significantly higher in person-years when people with AUD reported not drinking or person-years when people without AUD reported drinking at any level. No level of alcohol use may be "safe" for people with a prior AUD with regard to maintaining viral suppression.

Methylomic and transcriptomic predictors of one-month exposure to cortisol in healthy individuals.

Allostatic load (AL) refers to the cumulative "wear and tear" on an organism throughout its lifetime. One of the primary contributing factors to AL is prolonged exposure to stress or its primary catabolic agent cortisol. Chronic exposure to stress or cortisol is associated with numerous diseases, including cardiovascular disease, metabolic disorders, and psychiatric disorders. Therefore, a molecular marker capable of integrating a past history of cortisol exposure would be of great utility for assessing disease risk. To this end, we recruited 87 healthy males and females of European ancestry between 18 and 60 years old, extracted genomic DNA and RNA from leukocytes, and implemented a gene-centric DNA enrichment method coupled with bisulfite sequencing and RNA-Seq of total RNA for the determination of genome-wide methylation and gene transcription, respectively. Sequencing data were analyzed against awakening and bedtime cortisol data to identify differentially methylated regions (DMRs) and CpGs (DMCs) and differentially expressed genes (DEGs). Six candidate DMCs (punadjusted < 0.005) and nine DEGs (punadjusted < 0.0005) were used to construct a prediction model that could capture past 30+ days of both bedtime and awakening cortisol levels. Utilizing a cross-validation approach, we obtained a regression coefficient of R2 = 0.308 for predicting continuous awakening cortisol and an area under the curve (AUC) = 0.753 for dichotomous (high vs. low tertile) awakening cortisol, and R2 = 0.224 and AUC = 0.723 for continuous and dichotomous bedtime cortisol levels, respectively. To our knowledge, the current study represents the first attempt to identify genome-wide predictors of cortisol exposure that utilizes both methylation and transcription targets. The utility of our approach needs to be replicated in an independent cohort of samples for which similar cortisol metrics are available.

Decreased Alcohol Consumption in an Implementation Study of Computerized Brief Intervention among HIV Patients in Clinical Care.

This prospective, nonrandomized implementation study evaluated a computerized brief intervention (CBI) for persons with HIV (PWH) and heavy/hazardous alcohol use. CBI was integrated into two HIV primary care clinics. Eligible patients were engaged in care, ≥ 18 years old, English speaking, endorsed heavy/hazardous alcohol use on the Alcohol Use Disorders Identification Test-C (AUDIT-C). Two 20-min computerized sessions using cognitive behavioral techniques were delivered by a 3-D avatar on touch screen tablets. Of 816 eligible AUDIT-C scores, 537 (66%) resulted in CBI invitation, 226 (42%) of invited patients enrolled, and 176 (78%) of enrolled patients watched at least one session. CBI enrollment was associated with a significant average reduction of 9.1 drinks/week (95% CI - 14.5, - 3.6) 4-12 months post-enrollment. Among those who participated in one or both sessions, average reduction in drinks/week was 11.7 drinks/week (95% CI - 18.8, - 4.6). There was corresponding improvement in AUDIT-C scores. Overall patients reported high levels of intervention satisfaction, particularly among older and Black patients. These promising results point to a practical intervention for alcohol reduction in this vulnerable patient population with elevated rates of heavy/hazardous drinking. Future research should examine strategies to increase initial engagement, strengthen intervention effects to increase the number of patients who achieve non-hazardous drinking, and examine the duration of therapeutic effects.

Changing Patterns of Alcohol Use and Probability of Unsuppressed Viral Load Among Treated Patients with HIV Engaged in Routine Care in the United States.

We examined HIV viral load non-suppression ([Formula: see text] 200 copies/mL) subsequent to person-periods (3-18 months) bookended by two self-reports of alcohol use on a standardized patient reported outcome assessment among adults in routine HIV care. We examined the relative risk (RR) of non-suppression associated with increases and decreases in alcohol use (relative to stable use), stratified by use at the start of the person-period. Increases in drinking from abstinence were associated with higher risk of viral non-suppression (low-risk without binge: RR 1.16, 95% CI 1.03, 1.32; low-risk with binge: RR 1.35, 95% CI 1.11, 1.63; high-risk: RR 1.89, 95% CI 1.16, 3.08). Decreases in drinking from high-risk drinking were weakly, and not statistically significantly associated with lower risk of viral non-suppression. Other changes in alcohol use were not associated with viral load non-suppression. Most changes in alcohol consumption among people using alcohol at baseline were not strongly associated with viral non-suppression.

Drug and alcohol use among people living with HIV in care in the United States by geographic region.

Substance use in the U.S. varies by geographic region. Opioid prescribing practices and marijuana, heroin, and methamphetamine availability are evolving differently across regions. We examined self-reported substance use among people living with HIV (PLWH) in care at seven sites from 2017-2019 to understand current regional substance use patterns. We calculated the percentage and standardized percentage of PLWH reporting current drug use and at-risk and binge alcohol use by U.S. Census Bureau geographic region and examined associations in adjusted logistic regression analyses. Among 7,686 PLWH, marijuana use was the most prevalent drug (30%), followed by methamphetamine/crystal (8%), cocaine/crack (7%), and illicit opioids (3%). One-third reported binge alcohol use (32%). Differences in percent of current use by region were seen for marijuana (24-41%) and methamphetamine/crystal (2-15%), with more use in the West and Northeast, and binge alcohol use (26-40%). In adjusted analyses, PLWH in the Midwest were significantly less likely to use methamphetamine/crystal (aOR: 0.13;0.06-0.25) or illicit opioids (aOR:0.16;0.05-0.53), and PLWH in the Northeast were more likely to use cocaine/crack (aOR:1.59;1.16-2.17), compared to PLWH in the West. Understanding differences in substance use patterns in the current era, as policies continue to evolve, will enable more targeted interventions in clinical settings among PLWH.

Changes in Hemodynamic Response Function Resulting From Chronic Alcohol Consumption.

BACKGROUND: Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known. METHODS: Participants with AUD and controls (CTL) received structural, functional, and vascular scans. During fMRI, participants were cued to tap their fingers, and averaged responses were extracted from the motor cortex. Curve fitting on these HRFs modeled them as a difference between 2 gamma distributions, and the temporal occurrence of the main peak and undershoot of the HRF was computed from the mean of the first and second gamma distributions, respectively. RESULTS: ANOVA and regression analyses found that the timing of the HRF undershoot increased significantly as a function of total lifetime drinking. Although gray matter volume in the motor cortex decreased with lifetime drinking, this was not sufficient to explain undershoot timing shifts, and vascular factors measured in the motor cortex did not differ among groups. Comparison of random-effects analyses using custom-fitted and canonical HRFs for CTL and AUD groups showed better results throughout the brain for custom-fitted versus canonical HRFs for CTL subjects. For AUD subjects, the same was true except for the basal ganglia. CONCLUSIONS: These findings suggest that excessive alcohol consumption is associated with changes in the HRF undershoot. HRF changes could provide a possible biomarker for the effects of lifetime drinking on brain function. Changes in HRF topography affect fMRI activation measures, and subject-specific HRFs generally improve fMRI activation results.

Neural Substrates Underlying Eyeblink Classical Conditioning in Adults With Alcohol Use Disorders.

BACKGROUND: Excessive alcohol consumption produces changes in the brain that often lead to cognitive impairments. One fundamental form of learning, eyeblink classical conditioning (EBC), has been widely used to study the neurobiology of learning and memory. Participants with alcohol use disorders (AUD) have consistently shown a behavioral deficit in EBC. The present functional magnetic resonance imaging (fMRI) study is the first to examine brain function during conditioning in abstinent AUD participants and healthy participants. METHODS: AUD participants met DSM-IV criteria for alcohol dependence, had at least a 10-year history of heavy drinking, and were abstinent from alcohol for at least 30 days. During fMRI, participants received auditory tones that predicted the occurrence of corneal airpuffs. Anticipatory eyeblink responses to these tones were monitored during the experiment to assess learning-related changes. RESULTS: Behavioral results indicate that AUD participants showed significant conditioning deficits and that their history of lifetime drinks corresponded to these deficits. Despite this learning impairment, AUD participants showed hyperactivation in several key cerebellar structures (including lobule VI) during conditioning. For all participants, history of lifetime drinks corresponded with their lobule VI activity. CONCLUSIONS: These findings suggest that excessive alcohol consumption is associated with abnormal cerebellar hyperactivation and conditioning impairments.

Psychiatric Disorders and Substance Use Among African American Women in HIV Care.

African-American (AA) women are overrepresented among women with HIV (WWH). In the United States, psychiatric disorders are prevalent among WWH and associated with adverse outcomes. However, little research has examined psychiatric disorders among AA WWH. 315 AA women who were hazardous/heavy drinkers (HD) or moderate/non-drinkers (ND) were recruited from an HIV clinic in a study on alcohol use disorders. We compared sample prevalence of Axis-1 psychiatric diagnoses using the Structured Clinical Interview for DSM-IV with those from general population AA women in the National Comorbidity Survey-Replication (NCS-R). While 29.9% of general population AA women had any lifetime disorder, 66.9% of HD and 62.4% of ND WWH met criteria for a lifetime Axis-1 disorder. Specifically, lifetime PTSD and lifetime MDD were over threefold higher; current PTSD and current MDD respectively were 11-fold and threefold higher. PTSD was the most frequent comorbid diagnosis. HD and ND WWH did not differ in prevalence of psychiatric diagnoses despite significantly higher rates of substance use among HD women. Diagnostic evaluation and intervention for psychiatric disorders should be a priority in HIV medical care settings to improve health outcomes. Interventions should be tailored to address the particular stressors, challenges, and resiliencies among AA WWH.

The Relationship of Varenicline Agonism of α4ß2 Nicotinic Acetylcholine Receptors and Nicotine-Induced Dopamine Release in Nicotine-Dependent Humans.

INTRODUCTION: Cigarette smoking continues to be one of the most important behavioral causes of morbidity and mortality in the world. Varenicline, an α4ß2 nicotinic acetylcholine receptor (nAChR) partial agonist, has been shown to increase smoking quit rates compared with nicotine-based products. This human laboratory, double-blind, placebo-controlled study examined varenicline and placebo effects on α4ß2-nAChRs occupancy, nicotine-induced change in [11C]raclopride non-displaceable binding potential (BPND), and behavioral measures of cigarette smoking, nicotine craving, and withdrawal. METHODS: Current nicotine dependent daily smokers (N = 17) were randomized to varenicline 1 mg twice daily or placebo for 13 days. Using positron emission tomography), we characterized α4ß2-nAChRs occupancy using [18F]AZAN and dopamine receptor binding using [11C]raclopride as well as behavioral measures of cigarettes smoked, craving, and nicotine withdrawal. RESULTS: Varenicline compared with placebo resulted in significant reductions in [18F]AZAN BPND in multiple brain regions including thalamus, midbrain, putamen, and ventral striatum. Following administration of a controlled-dose nicotine cigarette, dopamine release was significantly suppressed in the ventral striatum in the varenicline-treated compared with the placebo group. There was a significant relationship between α4ß2-nAChRs BPND measured in thalamus during the [18F]AZAN scan and nicotine-induced change in raclopride BPND in the ventral striatum. CONCLUSION: This is the first human study to demonstrate a direct relationship between the extent of varenicline occupancy of α4ß2-nAChRs and the magnitude of dopamine release following nicotine use. IMPLICATIONS: It has remained unclear how nicotinic receptor blockade through partial agonist medications such as varenicline promotes smoking cessation. One hypothesized mechanism is downstream dampening of the mesolimbic reward dopamine system. For the first time in human smokers, we observed a direct relationship between the extent of varenicline blockade of α4ß2-nACh nicotinic receptors and the magnitude of dopamine release following smoking. This has mechanistic and therapeutic implications for improving smoking cessation interventions.

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95-1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74-0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

Alcohol Use Patterns and Subsequent Sexual Behaviors Among Women, Men who have Sex with Men and Men who have Sex with Women Engaged in Routine HIV Care in the United States.

Among people with HIV, alcohol use is associated with increased prevalence of sexual transmission behaviors. We examined associations between alcohol use in the prior year and sexual behaviors approximately six months later among 1857 women, 6752 men who have sex with men (MSM) and 2685 men who have sex with women (MSW). Any alcohol use was associated with increased risk of unsafe vaginal sex among women; anal sex and =>2 anal sex partners among MSM; and anal sex, =>2 anal or vaginal sex partners, and unsafe vaginal sex among MSW. In particular, among women >7 alcoholic drinks/week and among MSW =>5 alcoholic drinks/drinking day increased the likelihood of certain subsequent sexual behaviors. For all groups, especially women, the risk of sex under the influence of drugs/alcohol markedly increased with increases in quantity and frequency of alcohol consumption. These different patterns of drinking and sexual behaviors indicate the importance of tailored counseling messages to women, MSM and MSW.

The relationship between alcohol use and anxiety and retrospective attendance of primary care visits among women with human immunodeficiency virus.

In this retrospective study, we sought to determine the associations between alcohol use and anxiety and RIC among WHIV. Alcohol use was assessed using the Timeline Follow-back to measure use over the 90 days preceding the interview. Anxiety symptoms scores, assessed with the Hospital Anxiety and Depression Scale- Anxiety Subscale (HADS-A). Primary care visits over twelve months prior to the interview were collected from clinic registration records. We used three logistic mixed models, adjusting for age, race, education, cocaine use, depression, viral load, and antiretroviral therapy (ART) status. Among 364 WHIV, mean attendance of primary care visits was 63.9%. Every one-day increase in drinking days (OR = 0.99, 95% CI 0.99, 1.00) or heavy drinking days (OR = 0.99, 95% CI 0.90, 1.00) was associated with decreased odds of attending primary care visits (P = 0.02). Moderate/severe anxiety scores, compared to minimal anxiety scores, were associated with decreased odds of attending primary care visits (OR = 0.69, 95% CI 0.50, 0.97). Cocaine use was associated with decreased odds of attending primary care visits (OR 0.56, 0.57). Our findings indicate that identifying and treating WHIV with alcohol use (especially heavy drinking), moderate/severe anxiety symptoms and/or cocaine use could potentially improve their RIC.

Detecting Deception in Our Research Participants: Are Your Participants Who You Think They Are?

There is increasing awareness of the potential negative impacts of participant deception on research, including possibly undermining reliability and reproducibility of study findings. These deceptive individuals set their personal interests above the rules of study participation, thereby jeopardizing data quality as well as placing themselves and others at risk. The costs of participant deception are numerous. Overall, it reduces statistical power and may even result in false conclusions about efficacy and safety. To date, most studies have not utilized sufficient methods to detect rule-breaking subjects. The purpose of this article is to bring to the attention of alcohol and other drug researchers issues involving deceptive participants. The review will suggest alcohol-specific as well as more general strategies to identify and thereby minimize enrollment of these deceptive participants. Specifically, we will identify strategies that are employed in different phases of human alcohol research and advance approaches that may be helpful to the field in reducing these contaminants. As a field, we need to be more proactive in identifying the deceptive participant even at the cost of more burdensome study enrollment. In light of the systemic nature and multipronged damage that this emerging pattern of deception inflicts on clinical research, it is imperative that we each assume greater responsibility for our role in mitigating this source of research contamination.

Predictors of Longitudinal Trajectories of Alcohol Consumption in People with HIV.

BACKGROUND: Our aim was to describe alcohol consumption trajectories in a cohort of people living with HIV and determine clinical and sociodemographic predictors of each trajectory. METHODS: This is a prospective cohort study of 7,906 patients in the 7 Centers for AIDS Research Network of Integrated Clinical Systems sites. Alcohol consumption was categorized as none, moderate, and alcohol misuse. Predictors included age, race/ethnicity, depressive or anxiety symptoms, illicit drug use (opioids, methamphetamines, cocaine/crack), marijuana use, hepatitis C virus (HCV) infection, HIV transmission risk factor, and HIV disease progression. We estimated sex-stratified alcohol consumption trajectories and their predictors. RESULTS: We found 7 trajectories of alcohol consumption in men: stable nondrinking and increased drinking (71% and 29% of initial nondrinking); stable moderate, reduced drinking, and increased alcohol misuse (59%, 21%, and 21% of initial moderate alcohol use); and stable alcohol misuse and reduced alcohol misuse (75% and 25% of initial alcohol misuse). Categories were similar in women, except lack of an increase to alcohol misuse trajectory among women that begin with moderate use. Older men and women were more likely to have stable nondrinking, while younger men were more likely to increase to or remain in alcohol misuse. Minorities, people with depressive or anxiety symptoms, HCV-infected individuals, and people who injected drugs were more likely to reduce use. Illicit drug use was associated with a reduction in overall drinking, while marijuana use was associated with stable moderate drinking or misuse. CONCLUSIONS: Longitudinal trajectories of increasing alcohol use and stable misuse highlight the need to integrate routine screening and alcohol misuse interventions into HIV primary care.

The role of personal and household members' substance use in health-related quality of life in women living with HIV/AIDS.

Advances in HIV treatments have led to a greater focus on health-related quality of life (HRQOL) among people living with HIV/AIDS. The current study examined factors associated with HRQOL among 378 women in HIV care. HRQOL was measured using a modified version of the 12-Item Short Form Health Survey; scores were derived for the mental and physical composite summaries (MCS and PCS). We measured personal alcohol use and drug use. Household members' substance use were assessed by asking participants about the alcohol/drug status of persons with whom they live. Multivariate generalized linear models were used to estimate the linear association between MCS and PCS scores and personal and household members' alcohol and drug use. We found lower MCS scores were significantly associated with personal alcohol use and living with someone with alcohol or/and drug problems. Lower PCS scores were not significantly associated with personal alcohol use or living with someone with alcohol or/and drug problems. Findings suggest that universal screening and targeted interventions for alcohol use by the patient or household members may offer potential strategies for improving mental health quality of life among women living with HIV/AIDS.

A paradigm for examining stress effects on alcohol-motivated behaviors in participants with alcohol use disorder.

Although epidemiological research has shown an increase in drinking following stressors and trauma, limited paradigms have been validated to study the relationship between stress and drinking in the human laboratory. The current study developed a progressive ratio (PR) operant procedure to examine the effects of psychosocial stress on alcohol craving and several alcohol-motivated behaviors in persons with alcohol use disorder. Current heavy, nontreatment-seeking drinkers (N = 30) were media-recruited and completed a comprehensive assessment of recent drinking, mood and health. Participants were admitted to the clinical research unit and underwent 4-day, physician-monitored alcohol abstinence. On days 4 and 5, participants underwent the Trier Social Stress Test or a neutral session in random order followed by the alcohol-motivated response (AMR) procedure in which subjects worked for money or alcohol under a PR operant procedure. Subjects received earned money vouchers or alcohol at the conclusion of the session. The Trier Social Stress Test increased alcohol craving and rate of responding and decreased the number of changeovers between alcohol versus money reinforcers on the PR schedule. There was a positive relationship between alcohol craving and drinks earned during the stress session. This novel paradigm provides an experimental platform to examine motivation to drink without confounding by actual alcohol ingestion during the work session, thereby setting the stage for future studies of alcohol interventions.

Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.

BACKGROUND: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. METHODS: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol contents (0.03 to 0.1%). DNA was analyzed for OPRM1 AA versus AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) versus 9 or lesser alleles (A9), and ancestral informative markers. RESULTS: There were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective High Assessment Scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele. CONCLUSIONS: These findings highlight the biological importance of interactions between these 2 genes and interactions between brain opioid and dopamine systems.