Sensitivity, specificity, and tolerability of the BACTrack Skyn compared to other alcohol monitoring approaches among young adults in a field-based setting.

BACKGROUND: There is a need for novel alcohol biosensors that are accurate, able to detect alcohol concentration close in time to consumption, and feasible and acceptable for many clinical and research applications. We evaluated the field accuracy and tolerability of novel (BACTrack Skyn) and established (Alcohol Monitoring Systems SCRAM CAM) alcohol biosensors. METHODS: The sensor and diary data were collected in a larger study of a biofeedback intervention and compared observationally in the present sub-study. Participants (high-risk drinkers, 40% female; median age 21) wore both Skyn and SCRAM CAM sensors for 1-6 days and were instructed to drink as usual. Data from the first cohort of participants (N = 27; 101 person-days) were used to find threshold values of transdermal alcohol that classified each day as meeting or not meeting defined levels of drinking (heavy, above-moderate, any). These values were used to develop scoring metrics that were subsequently tested using the second cohort (N = 20; 57 person-days). Data from both biosensors were compared to mobile diary self-report to evaluate sensitivity and specificity in relation to a priori standards established in the literature. RESULTS: Skyn classification rules for Cohort #1 within 3 months of device shipment showed excellent sensitivity for heavy drinking (94%) and exceeded expectations for above-moderate and any drinking (78% and 69%, respectively), while specificity met expectations (91%). However, classification worsened when Cohort #1 devices ≥3 months from shipment were tested (area under curve for receiver operator characteristic 0.87 vs. 0.79) and the derived classification threshold when applied to Cohort #2 was inadequately specific (70%). Skyn tolerability metrics were excellent and exceeded the SCRAM CAM (p ≤ 0.001). CONCLUSIONS: Skyn tolerability was favorable and accuracy rules were internally derivable but did not yield useful scoring metrics going forward across device lots and months of usage.

Within- and between-person effects of naltrexone on the subjective response to alcohol and craving: A daily diary investigation.

OBJECTIVE: Naltrexone is an effective treatment for heavy drinking among young adults. Laboratory-based studies have shown that naltrexone dampens the subjective response to alcohol and craving. However, few studies have tested naltrexone's dynamic, within-person effects on subjective response and craving among young adults in natural drinking environments. METHODS: Using daily diary data from a randomized, placebo-controlled study of naltrexone's efficacy in young adults, we examined the between-person effects of treatment condition (i.e., naltrexone vs. placebo) and medication dosage (i.e., daily, targeted, and daily + targeted) on the subjective response to alcohol and craving on drinking days. Multilevel mediation models predicted subjective response and craving from treatment condition (between-person) and medication dosage (within-person), accounting for drinking levels. All effects were disaggregated within and between persons. RESULTS: At the between-person level, naltrexone directly blunted intense subjective effects (i.e., "impaired", "drunk") and indirectly blunted subjective effects through reduced drinking. Naltrexone was not associated with craving. Between-person effects were not significant after alpha correction, but their effect sizes (bs = 0.14 to 0.17) exceeded the smallest effect size of interest. At the within-person level, taking two (vs. 1) pills was associated with heavier drinking, and taking one (vs. 0) pill was associated with lighter drinking, and lighter drinking was associated with a lower subjective response and craving. Treatment condition did not moderate the within-person effects of dosing on outcomes. CONCLUSIONS: Our findings suggest that the direct between-person effect of naltrexone was largest on intense subjective responses, blunting feelings of being "drunk" and "impaired". Future research using momentary (rather than daily) assessments could confirm and extend these findings.

The Impact of Integrated Behavioral Healthcare on Glycemic Control.

Integrated behavioral healthcare (IBH) is the "standard of care" to address psychosocial factors impacting diabetes outcomes; it is not standard in practice. This longitudinal, retrospective, chart-review examines IBH impact on glycemic control in an adult diabetes clinic. Adults (n = 374) with ≥ 1 behavioral health encounter, ≥ 2 hemoglobin A1c (HbA1c) values, and HbA1c value > 8% at initial IBH visit were included. Mixed effects linear piecewise models examined differences in slope trajectories for 365 days pre- and post-IBH intervention. Pre-intervention slope was not significant (z = - 1.09, p = 0.28). The post-intervention slope was significant (z = - 6.44, p < 0.001), indicating a significant linear decrease in HbA1c values. Results demonstrated that prior to engaging with behavioral health, there was no change in HbA1c. After initial IBH visit, there was a predicted reduction of > 1% in HbA1c over the following year. These results suggest that IBH significantly improves patients' metabolic status. Next steps for IBH research are offered.

Mapping data-driven individualized neurobehavioral phenotypes in heavy alcohol drinkers.

OBJECTIVE: Recent studies have examined the factor structure and associated correlates of three neurofunctional domains, executive function, incentive salience, and negative emotionality in the development and maintenance of alcohol use disorders in clinical samples. The current study sought to replicate and extend prior work by testing this 3-factor model, utilizing both exact and similar phenotypic measures, as well as novel measures, in a non-treatment-seeking sample. METHODS: Self-report measures of alcohol addiction, impulsivity, behavior, and exposure to early-life stress were collected as part of baseline assessments for alcohol imaging and pharmacotherapy studies in 335 individuals. Confirmatory factor analysis (CFA) was used to examine model structure and fit. A multiple indicators, multiple causes (MIMIC) model identified predictors of latent factors identified by CFA. RESULTS: Results supported an intercorrelated model with three factors: executive function, incentive salience, and emotionality. All factors were associated with current AUD, and incentive salience was uniquely associated with past 30-day drinking frequency. MIMIC results identified multiple significant predictors of these latent factors, including history of alcohol use disorder, positive family history of alcohol dependence, earlier age of first drink, and a history of childhood emotional abuse and physical neglect. CONCLUSIONS: Our results support an intercorrelated 3-factor model of neurofunctional domains in alcohol use models, consistent with published findings. Because childhood physical neglect was a significant predictor of all latent factors, these results also highlight the significant negative impact of childhood neglect on later addiction development.

Drinking and responses to antidrinking messages among young adults: An fMRI study.

Young adults consume most of their alcohol by binge drinking, and more than one-third report binge drinking in the past month. Some will transition out of excessive drinking, while others will maintain or increase alcohol use into adulthood. Public health campaigns depicting negative consequences of drinking have shown some efficacy at reducing this behavior. However, substance use in dependent individuals is governed in part by automatic or habitual responses to drug cues rather than the consequences. This study used functional magnetic resonance imaging to measure neural responses to drinking cues and drinking cues paired with antidrinking messages among young adults who binge drink (N = 30). This study also explored responses to smoking cues and antismoking messages. Neural responses were also compared between drinking/smoking and neutral cues. Self-reported drinking and smoking were collected at baseline, postscan, and 1 month. Results indicate that activity in the ventral striatum-implicated in reward processing-was lower for drinking cues paired with antidrinking messages than drinking cues. This difference was less pronounced in young adults who reported greater baseline past month drinking quantity. Past month drinking quantity decreased from baseline to 1 month. Further, young adults who showed higher activity during antidrinking messages in the medial prefrontal cortex-implicated in processing message self-relevance- reported a greater decrease in past month drinking frequency from baseline to 1 month. Findings may help to identify young adults who are at risk for continued heavy drinking in adulthood and inform interventions aimed to reduce drinking and reward in young adults.

Examining the Relationship Between Self-Reported Drinking and In-Laboratory Drinking and Craving: Is There Concordance?

BACKGROUND: In-laboratory drinking sessions that allow direct assessment of drinking and craving are an emerging method for testing novel pharmacotherapy compounds and behavioral interventions for alcohol use disorders. Despite wide implementation, limited evidence supports the concordance between drinking in the laboratory and in a natural setting. This study examined the relationship between self-reports of drinking prior to and drinking and craving during an alcohol drinking paradigm (ADP). METHODS: Participants were adult heavy drinkers (N = 64) who participated in a pharmacotherapy study. Participants completed self-report alcohol assessments and a baseline ADP session prior to any medication administration. Alcohol craving was assessed during priming and ad lib ADP phases. Outcomes were the associations of total drinks consumed in-laboratory and summary drinking measures for the 30 days prior to the ADP and reports of maximum drinks (past year and lifetime). Additional outcomes were the association of self-reported drinking and alcohol craving during the ADP and the concordance between self-report and ADP World Health Organization (WHO) drinking classifications. RESULTS: Number of drinking days, average drinks per drinking occasion, and lifetime and past-year maximum drinks were all related to drinking in the laboratory. Heavy drinking days were not related to drinking in the laboratory but were associated with ADP craving. Alcohol craving was also associated with other measures of self-reported drinking. There was also a significant association between WHO drinking risk classification and in-laboratory drinking. CONCLUSIONS: The observed relationships between self-reported drinking and drinking in-laboratory across drinking indices suggest that in-laboratory alcohol consumption may reflect participants' real-world alcohol consumption, supporting the value of laboratory-based drinking paradigms. The demonstrated relationship with self-reported drinking and ADP alcohol craving further supports the value of such paradigms to model key drinking predictors. These results provide support for the validity of laboratory-based paradigms to accurately reflect participants' recent drinking levels.

The Association of Impulsivity and Family History of Alcohol Use Disorder on Alcohol Use and Consequences.

BACKGROUND: Extensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems. METHODS: The data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source. RESULTS: Significant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found. CONCLUSIONS: These findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

Using Web-Based Social Media to Recruit Heavy-Drinking Young Adults for Sleep Intervention: Prospective Observational Study.

BACKGROUND: Novel alcohol prevention strategies are needed for heavy-drinking young adults. Sleep problems are common among young adults who drink heavily and are a risk factor for developing an alcohol use disorder (AUD). Young adults, interested in the connection between sleep and alcohol, are open to getting help with their sleep. Therefore, sleep interventions may offer an innovative solution. This study evaluates social media advertising for reaching young adults and recruiting them for a new alcohol prevention program focused on sleep. OBJECTIVE: This study aims to evaluate the effectiveness and cost of using Facebook, Instagram, and Snapchat advertising to reach young adults who drink heavily for a sleep intervention; characterize responders' sleep, alcohol use, and related concerns and interests; and identify the most appealing advertising content. METHODS: In study 1, advertisements targeting young adults with sleep concerns, heavy alcohol use, or interest in participating in a sleep program ran over 3 months. Advertisements directed volunteers to a brief web-based survey to determine initial sleep program eligibility and characterize the concerns or interests that attracted them to click the advertisement. In study 2, three advertisements ran simultaneously for 2 days to enable us to compare the effectiveness of specific advertising themes. RESULTS: In study 1, advertisements generated 13,638 clicks, 909 surveys, and 27 enrolled volunteers in 3 months across the social media platforms. Fees averaged US $0.27 per click, US $3.99 per completed survey, US $11.43 per volunteer meeting initial screening eligibility, and US $106.59 per study enrollee. On average, those who completed the web-based survey were 21.1 (SD 2.3) years of age, and 69.4% (631/909) were female. Most reported sleep concerns (725/909, 79.8%) and an interest in the connection between sleep and alcohol use (547/909, 60.2%), but few had drinking concerns (49/909, 5.4%). About one-third (317/909, 34.9%) were identified as being at risk for developing an AUD based on a validated alcohol screener. Among this subsample, 8.5% (27/317) met the final criteria and were enrolled in the trial. Some volunteers also referred additional volunteers by word of mouth. In study 2, advertisements targeting sleep yielded a higher response rate than advertisements targeting alcohol use (0.91% vs 0.56% click rate, respectively; P<.001). CONCLUSIONS: Social media advertisements designed to target young adults with sleep concerns reached those who also drank alcohol heavily, despite few being concerned about their drinking. Moreover, advertisements focused on sleep were more effective than those focused on drinking. Compared with previous studies, cost-effectiveness was moderate for engagement (impressions to clicks), excellent for conversion (clicks to survey completion), and reasonable for enrollment. These data demonstrate the utility of social media advertising focused on sleep to reach young adults who drink heavily and recruit them for intervention.

Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study.

BACKGROUND: Many liver transplantation programs require documented alcohol sobriety prior to United Network for Organ Sharing (UNOS) listing. This pilot study examined the feasibility of the first mobile, alcohol relapse prevention intervention for liver transplant patients with alcoholic liver disease (ALD). METHODS: This was a randomized 8-week pilot feasibility trial of a text message-based alcohol intervention. In-treatment assessment was conducted at 4 weeks (4W), and immediate posttreatment assessment was conducted at 8W. Participants were liver transplant candidates (N = 15) diagnosed with ALD who reported at least 1 drinking episode in the past year. Primary feasibility outcomes were percent of messages responded to and posttreatment intervention satisfaction ratings. Preliminary clinical efficacy outcomes were any biologically confirmed alcohol consumption, stress, abstinence self-efficacy, and alcohol craving. RESULTS: On feasibility outcomes, participants responded to 81% of messages received and reported high rates of intervention satisfaction, looked forward to receiving the messages, and found it easy to complete the intervention. On preliminary efficacy outcomes, zero participants in the text message (TM) had positive urine alcohol tests at 8W. Two of the 6 participants in standard care (SC) tested positive at 8W. No effects were seen on craving. For stress, a condition × time interaction emerged. TM participants had less stress at 4W and 8W compared with SC at baseline. They maintained their stress level during the intervention. For self-efficacy, a trend for condition effect emerged. TM participants had higher self-efficacy than SC participants. CONCLUSIONS: Participants reported high satisfaction with the intervention, looked forward to the messages, and found it easy to complete. Participants who received the intervention had better treatment outcomes than those who received standard care. They maintained higher levels of self-efficacy and lower stress. Mobile alcohol interventions may hold significant promise to help ALD liver transplant patients maintain sobriety.

A Test of Multisession Automatic Action Tendency Retraining to Reduce Alcohol Consumption Among Young Adults in the Context of a Human Laboratory Paradigm.

BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, and thus, novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. This study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration. METHODS: A total of 72 nontreatment-seeking, heavy drinking young adults ages 21 to 25 were randomized to automatic action tendency retraining or a control condition (i.e., "sham training"). Of these, 69 (54% male) completed 4 iterations of retraining or the control condition over 5 days with an alcohol drinking session on Day 5. Self-administration was conducted according to a human laboratory paradigm designed to model individual differences in impaired control (i.e., difficulty adhering to limits on alcohol consumption). RESULTS: Automatic action tendency retraining was not associated with greater reduction in alcohol approach tendency or less alcohol self-administration than the control condition. The laboratory paradigm was probably sufficiently sensitive to detect an effect of an experimental manipulation given the range of self-administration behavior observed, both in terms of number of alcoholic and nonalcoholic drinks and measures of drinking topography. CONCLUSIONS: Automatic action tendency retraining was ineffective among heavy drinking young adults without motivation to change their drinking. Details of the retraining procedure may have contributed to the lack of a significant effect. Despite null primary findings, the impaired control laboratory paradigm is a valid laboratory-based measure of young adult alcohol consumption that provides the opportunity to observe drinking topography and self-administration of nonalcoholic beverages (i.e., protective behavioral strategies directly related to alcohol use).

Using Sleep Interventions to Engage and Treat Heavy-Drinking College Students: A Randomized Pilot Study.

BACKGROUND: Continued high alcohol consumption levels by college students highlight the need for more effective alcohol interventions and novel treatment engagement strategies. The purpose of this study was to investigate a behavioral sleep intervention as a means to engage heavy-drinking college students in treatment and reduce alcohol use and alcohol-related consequences. METHODS: Heavy-drinking college students (N = 42) were assigned to 1 of 2 web-based interventions comprised of 4 modules delivered over 4 weeks. The experimental intervention focused primarily on sleep and included evidence-based sleep content (i.e., stimulus control instructions, sleep scheduling [consistent bed/rise times; ideal sleep duration for adolescents/young adults], sleep hygiene advice, relaxation training, cognitive strategies to target sleep-disruptive beliefs), and alcohol content (i.e., normative and blood alcohol level feedback, moderate drinking guidelines, controlled drinking strategies, effects of alcohol on sleep and the body, advice to moderate drinking for improved sleep) in young adults. The control condition Healthy Behaviors provided basic advice about nutrition, exercise, sleep (i.e., good sleep hygiene only), and drinking (i.e., effects of alcohol on the body, moderate drinking guidelines, advice to moderate drinking for sleep). Participants in both conditions monitored their sleep using daily web-based diaries and a wrist-worn sleep tracker. RESULTS: Recruitment ads targeting college students with sleep concerns effectively identified heavy-drinking students. The program generated a high number of inquiries and treatment completion rates were high. Both interventions significantly reduced typical week drinking and alcohol-related consequences and improved sleep quality and sleep-related impairment ratings. The control condition yielded greater reductions in total drinks in a heaviest drinking week. The effects on drinking were larger than those observed in typical brief alcohol intervention studies for college students. Greater sleep improvement tended to predict better subsequent drinking outcomes. CONCLUSIONS: The results suggest that sleep treatment may be a promising strategy for targeting and treating heavy-drinking college students.

Perceptions of Heavy-Drinking College Students About a Sleep and Alcohol Health Intervention.

The purpose of this mixed methods study was to describe the sleep and psychological characteristics of heavy-drinking college students, their perceptions of sleep and sleep/alcohol interactions, and their reactions to a proposed integrated sleep and alcohol Web-based intervention. Students (N = 24) completed standardized surveys and participated in semistructured focus group interviews. Participants reported a high degree of sleep disturbance, sleep obstacles, and sleep-related consequences, which were validated by both quantitative and qualitative investigations. Sleep disturbance and sleep-related impairment were associated with more frequent drinking and greater risks from drinking. Participants perceived that alcohol has positive and negative effects on sleep latency, continuity, and quality. They expressed overall enthusiasm for the intervention but had specific content and format preferences.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

Interventions to reduce alcohol use among HIV-infected individuals: a review and critique of the literature.

Alcohol use disorders are common among HIV-infected individuals and are associated with adverse physiological complications and increased engagement in other health risk behaviors. This paper provides a review and critique of interventions to reduce alcohol use among HIV-infected individuals, including a: (a) synthesis of core intervention components and trial designs; (b) summary of intervention efficacy to reduce alcohol use outcomes; and (c) methodological critique and guidance for future research. We reviewed 14 behavioral interventions that reported on alcohol use outcomes among HIV-infected individuals. Findings were mixed for intervention efficacy to reduce alcohol frequency and quantity. There was limited evidence that interventions reduced binge drinking frequency or alcohol abuse or dependence symptoms. Despite the prevalence of disordered alcohol use among HIV-infected individuals, there is lack of efficacious intervention approaches. Efficacious intervention approaches to reduce alcohol use among HIV-infected individuals are urgently needed.

Dynamic structural equation modeling of the relationship between alcohol habit and drinking variability.

BACKGROUND: A hyper-engaged habit system may be common in alcohol use disorders (AUDs). Regarding drinking patterns, habit may be expressed as higher levels of drinking autoregression, where previous day drinking is correlated with next day drinking. This study utilized dynamic structural equation models (DSEM) with intensive longitudinal data to understand whether alcohol habit relates to drinking autoregression and variable levels of alcohol consumption. METHODS: Participants were adult drinkers (N = 313) who completed baseline self-report assessments of past 30-day alcohol consumption and alcohol habit. Alcohol habit was measured by the Self Report Habit Index (SRHI). Thirty-day coding of the Timeline Followback assessed total daily drinking and any daily heavy drinking. RESULTS: The DSEM model for daily drinking found a weak but significant autoregressive data structure. Alcohol habit was related to increased mean drinking but did not strengthen the autoregressive effect of drinks per day. Higher alcohol habit was associated with higher levels of drinks per day person-specific variability. This pattern was replicated with the DSEM model for heavy drinking. Alcohol habit did not impact the autoregressive effect of heavy drinking but was associated with higher levels of heavy drinking. CONCLUSIONS: While both drinks per day and heavy drinking showed a significant autoregressive structure, evidence of alcohol habit did not strengthen this effect. Alcohol habit did impact drinking variability; higher alcohol habit is associated with greater levels of drinking variability and higher mean drinking. Strategies to regulate drinking variability, including heavier drinking occasions, could target AUD habit.

A Multimodal Mobile Sleep Intervention for Young Adults Engaged in Risky Drinking: Protocol for a Randomized Controlled Trial.

BACKGROUND: This paper describes the research protocol for a randomized controlled trial of a multimodal mobile sleep intervention for heavy-drinking young adults. Young adults report the highest rates of heavy, risky alcohol consumption and are a priority population for alcohol prevention and intervention efforts. Alcohol strategies that leverage other health concerns and use technology may offer an innovative solution. Poor sleep is common among young adults and is a risk factor for developing an alcohol use disorder. Moreover, young adults are interested in information to help them sleep better, and behavioral sleep interventions address alcohol use as a standard practice. OBJECTIVE: The primary aim of this study is to assess the effectiveness of a 2-week multimodal mobile sleep intervention for reducing drinks consumed per week among heavy-drinking young adults. We will explore the effects on alcohol-related consequences, assessing quantitative and qualitative sleep characteristics as secondary aims. The study's goals are to identify the optimal combination of sleep intervention components for improving drinking outcomes, the feasibility and acceptability of these components, and the potential mechanisms by which these components may promote alcohol behavior change. METHODS: Young adults (aged 18-25 years) who report recent heavy drinking will be randomly assigned to one of three conditions: mobile sleep hygiene advice (n=30), mobile sleep hygiene advice and sleep and alcohol diary self-monitoring (n=30), or mobile sleep hygiene advice, sleep and alcohol diary self-monitoring, and sleep and alcohol data feedback (n=60). For the feedback component, participants will complete two web-based sessions with a health coach during which they will receive summaries of their sleep and alcohol data, and the potential association between them along with brief advice tailored to their data. All participants will wear sleep and alcohol biosensors daily for 2 weeks for objective assessments of these outcomes. RESULTS: The study was funded by the National Institutes of Health in May 2018. Recruitment began in December 2018 and will be concluded in Spring 2021. As of February 4, 2021, we have enrolled 110 participants. CONCLUSIONS: Ultimately, this research could result in an efficacious, low-cost intervention with broad population reach through the use of technology. In addition, this intervention may substantially impact public health by reducing alcohol use disorder risk at a crucial developmental stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT03658954; https://clinicaltrials.gov/ct2/show/NCT03658954. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26557.

Individual differences in the associations between risk factors for alcohol use disorder and alcohol use-related outcomes.

BACKGROUND: Family history of alcohol use disorder; AUD (FH +) and impulsivity-related traits are known risk factors for problem drinking that have been investigated in predominately White samples. This cross-sectional study examined whether these risk factors vary by sex in the overall, majority White sample and in a Black subsample. METHOD: A model building regression procedure was used to investigate the combined effect of FH + and impulsivity-related traits on alcohol quantity, frequency, and problems by sex (overall sample: N = 757, 50% female, 73% White, agemean = 33.74, SD = 11.60; Black subsample: n = 138, 47% female, agemean = 33.60, SD = 9.87). RESULTS: Overall Sample. No sex differences were found in the compounding effects of FH + and impulsivity-related traits on alcohol outcomes. Males reported more physical, social, and overall alcohol-related problems than females. FH + was positively associated with all alcohol-related consequences. Poor self-regulation was the only trait associated with all alcohol outcomes. Black Subsample: A three-way interaction suggested a negative association between inhibition and frequency of alcohol use among FH + males only. A two-way interaction also suggested impulse control was associated with more interpersonal alcohol-related problems among males only. Main effects were also found in the expected direction such that higher impulsivity and FH + were associated with poorer alcohol outcomes. CONCLUSION: These findings suggest no sex differences in the overall sample in the interactive effects of established risk factors for AUD on alcohol outcomes, and that poor self-regulation may be key for personality-targeted alcohol prevention and intervention programs. Preliminary findings of sex differences in the Black subsample should be replicated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Reward drinking and naltrexone treatment response among young adult heavy drinkers.

AIMS: Theory-driven, exploratory study to: (i) identify a reward drinking phenotype in young adults; (ii) evaluate this phenotype as a predictor of naltrexone response; and (iii) examine mechanisms of naltrexone in reward drinkers. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: USA. PARTICIPANTS: A total of 128 young adult (ages 18-25) heavy drinkers. INTERVENTIONS: Naltrexone versus placebo. MEASUREMENTS: Daily surveys assessed affect, urge, drinking, and context. The Drinking Motives Questionnaire was used to identify phenotypes based on reward (enhancement motives) and relief (coping motives) drinking. FINDINGS: We identified three profiles: "Low reward/Low relief" (14.1%; low enhancement/low coping motives); "Reward drinkers" (62.2%; high enhancement/low coping motives); and "High reward/High relief" (22.7%; high enhancement/high coping motives). Among reward drinkers (versus low profile), naltrexone significantly reduced percent days drinking to intoxication (blood alcohol concentration [BAC] ≥0.08) (PDI) (d = 0.56; 95% CI [0.17, 0.96]) and percent high intensity drinking days (PHID) (8/10 drinks for women/men) (d = 0.32; 95% CI [0.01, 0.68]). Among the high reward/high relief profile drinkers (versus low profile), naltrexone reduced PHID (d = 0.69; 95% CI [0.02, 1.50]). Using profile-informed cutoffs and observed scores (for clinical applicability): (i) among cutoff-derived reward drinkers, we found a medium-to-large (d = 0.66; 95% CI [0.24, 1.16]) and small effect (d = 0.28; 95% CI [0.04, 0.72]) of naltrexone in reducing PDI and PHID, respectively; and (ii) among the cutoff-derived high reward/high relief subgroup, we found a medium-to-large effect (d = 0.63; 95% CI [0.05, 1.1]) of naltrexone in reducing PHID. Among reward drinkers (not other profiles), naltrexone reduced drinking on days a drinking event occurred by weakening the within-day association between positive affect and urges (P < 0.05). CONCLUSIONS: Naltrexone has pronounced effects in reducing risky drinking among young adult reward drinkers (high reward/low relief) by reducing urges on days when individuals have higher positive affect and are exposed to a drinking event. Naltrexone also appears to reduce risky drinking among young adult high reward/high relief drinkers, but not via the same mechanism.

Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants.

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit. The Src/Fyn kinase inhibitor saracatinib (AZD0530) reduces ethanol self-administration and enhances extinction of goal-directed ethanol-seeking in mice. However, less is known regarding how saracatinib affects habitual ethanol-seeking. Moreover, no prior studies have assessed the effects of Src/Fyn kinase inhibitors on alcohol-seeking or consumption in human participants. Here, we tested the effects of saracatinib on alcohol consumption and craving/seeking in two species, including the first trial of an Src/Fyn kinase inhibitor to reduce drinking in humans. Eighteen male C57BL/6NCrl mice underwent operant conditioning on a variable interval schedule to induce habitual responding for 10% ethanol/0.1% saccharin. Next, mice received 5 mg/kg saracatinib or vehicle 2 h or 30 min prior to contingency degradation to measure habitual responding. In the human study, 50 non-treatment seeking human participants who drank heavily and met DSM-IV criteria for alcohol abuse or dependence were randomized to receive 125 mg/day saracatinib (n = 33) or placebo (n = 17). Alcohol Drinking Paradigms (ADP) were completed in a controlled research setting: before and after 7-8 days of treatment. Each ADP involved consumption of a priming drink of alcohol (0.03 mg%) followed by ad libitum access (3 h) to 12 additional drinks (0.015 g%); the number of drinks consumed and craving (Alcohol Urge Questionnaire) were recorded. In mice, saracatinib did not affect habitual ethanol seeking or consumption at either time point. In human participants, no significant effects of saracatinib on alcohol craving or consumption were identified. These results in mice and humans suggest that Fyn kinase inhibition using saracatinib, at the doses tested here, may not reduce alcohol consumption or craving/seeking among those habitually consuming alcohol, in contrast to reports of positive effects of saracatinib in individuals that seek ethanol in a goal-directed manner. Nevertheless, future studies should confirm these negative findings using additional doses and schedules of saracatinib administration.

Heightened muscle tension and diurnal hyper-vigilance following exposure to a social defeat-conditioned odor cue in rats.

Patients with post-traumatic stress disorder (PTSD) exhibit exaggerated daytime muscle tension as well as nocturnal sleep disturbances. Yet, these physiological and behavioral features of the disorder are little studied in animal models of PTSD. Accordingly, the present studies were designed to assess alterations in muscle tension and diurnal hyper-vigilance resulting from exposure to a social defeat stressor paired with an olfactory stimulus, which was then used as a reminder of stressor exposure. In the first series of experiments, rats presented with an olfactory cue paired previously with a single social defeat exhibited a significant increase in muscle tension 4 weeks following defeat. In the second series of experiments, an olfactory cue paired previously with a single social defeat induced a significant increase in locomotor activity among quiescent rats 4 weeks following stressor exposure. The present results thus support the a priori hypotheses that novel physiological and behavioral hallmarks of PTSD can be documented in an animal model of the disorder and that the present overt signs of reactive hyper-vigilance can be triggered by reintroduction of an olfactory stimulus present at the time of initial trauma exposure.