Meta-analysis of acute alcohol effects on response inhibition.

Alcohol intoxication impairs response inhibition; however, discrepant findings have been reported regarding the magnitude and moderators of this effect. This meta-analysis of human laboratory studies aimed to quantify acute effects of alcohol on response inhibition and evaluate moderators of this effect. Eligible studies examined alcohol's effects on response inhibition with the Go/No-Go (GNG) task (n = 1616 participants) or Stop Signal Task (SST) (n = 1310 participants). Results revealed a detrimental effect of acute alcohol on response inhibition overall (g = 0.411, 95 % CI [0.350, 0.471]), with similar effects in studies using GNG (g = 0.431, SE = 0.031) and SST (g = 0.366, SE = 0.063). Effect sizes were larger in studies involving higher breath alcohol concentration levels and under GNG conditions that established a prepotent response set. These findings establish the magnitude, precision, and potential moderators of alcohol's effects on inhibitory control, furthering understanding of a key neurobehavioral mechanism proposed to underlie alcohol-related impulsivity and impaired control over consumption.

Association Between Fatty Acid Amide Hydrolase and Alcohol Response Phenotypes: A Positron Emission Tomography Imaging Study With [11C]CURB in Heavy-Drinking Youth.

BACKGROUND: Reductions in fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid anandamide, may play a role in drinking behavior and risk for alcohol use disorder. We tested the hypotheses that lower brain FAAH levels in heavy-drinking youth are related to increased alcohol intake, hazardous drinking, and differential response to alcohol. METHODS: FAAH levels in the striatum, prefrontal cortex, and whole brain were determined using positron emission tomography imaging of [11C]CURB in heavy-drinking youth (N = 31; 19-25 years of age). C385A FAAH genotype (rs324420) was determined. Behavioral (n = 29) and cardiovascular (n = 22) responses to alcohol were measured during a controlled intravenous alcohol infusion. RESULTS: Lower [11C]CURB binding was not significantly related to frequency of use but was positively associated with hazardous drinking and reduced sensitivity to the negative effects of alcohol. During alcohol infusion, lower [11C]CURB binding related to greater self-reported stimulation and urges and lower sedation (p < .05). Lower heart rate variability was related to both greater alcohol-induced stimulation and lower [11C]CURB binding (p < .05). Family history of alcohol use disorder (n = 14) did not relate to [11C]CURB binding. CONCLUSIONS: In line with preclinical studies, lower FAAH in the brain was related to a dampened response to the negative, impairing effects of alcohol, increased drinking urges, and alcohol-induced arousal. Lower FAAH might alter positive or negative effects of alcohol and increase urges to drink, thereby contributing to the addiction process. Determining whether FAAH influences motivation to drink through increased positive/arousing effects of alcohol or greater tolerance should be investigated.

Exploring regulation and function of dopamine D3 receptors in alcohol use disorder. A PET [11C]-(+)-PHNO study.

Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD). In animals, voluntary alcohol consumption increases DRD3 expression, and pharmacological blockade of DRD3s attenuates alcohol self-administration and reinstatement of alcohol seeking. However, these findings have yet to be translated in humans. This study used positron emission tomography (PET) and [11C]-(+)-PHNO to compare receptor levels in several dopamine D2 receptor (DRD2) and DRD3 regions of interest between AUD subjects in early abstinence (n = 17; 6.59 ± 4.14 days of abstinence) and healthy controls (n = 18). We recruited non-treatment seeking subjects meeting DSM-5 criteria for AUD. We examined the relationship between DRD2/3 levels and both alcohol craving and alcohol motivation/wanting, using a cue reactivity procedure and an intravenous alcohol self-administration (IVASA) paradigm, respectively. [11C]-(+)-PHNO binding levels in AUD subjects were significantly lower than binding in HCs when looking at all DRD2/3 ROIs jointly (Wilk's Λ = .58, F(6,28) =3.33, p = 0.013, η2p = 0.42), however there were no region-specific differences. Binding values demonstrate -12.3% and -16.1% lower [11C]-(+)-PHNO binding in the SMST and SN respectively, though these differences did not withstand Bonferroni corrections. There was a positive association between [11C]-(+)-PHNO binding in the SN (almost exclusively reflective of DRD3) and alpha (lower values reflect higher alcohol demand) in the APT after Bonferroni corrections (r = 0.66, p = 0.0080). This demonstrates that AUD subjects with lower DRD3 levels in the SN exhibit increased demand for alcohol. These results replicate previous findings demonstrating reduced DRD2/3 levels while also supporting a lack of DRD3 upregulation and potential downregulation in early abstinent AUD. Furthermore, the finding that binding in the SN is associated with alcohol demand warrants further examination.

Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy-Drinking Youth.

BACKGROUND: Reduced function of fatty acid amide hydrolase, the catabolic enzyme for the endocannabinoid anandamide, can be inherited through a functional genetic polymorphism (FAAH rs324420, C385A, P129T). The minor (A) allele has been associated with reduced FAAH enzyme activity and increased risk for substance use disorders in adults. Whether this inherited difference in endocannabinoid metabolism relates to alcohol use disorder etiology and patterns of alcohol use in youth is unknown. METHODS: To examine this question, heavy-drinking youth (n = 302; mean age = 19.74 ± 1.18) were genotyped for FAAH C385A. All subjects completed a comprehensive interview assessing alcohol use patterns including the Timeline Follow-back Method, Alcohol Use Disorders Identification Test (AUDIT), and Drinking Motives Questionnaire. Analyses of Covariance (ANCOVAs) were conducted to assess differences in drinking patterns and drinking motives between genotype groups, and mediation analyses investigated whether drinking motives accounted for indirect associations of genotype with alcohol use severity. RESULTS: Youth with the FAAH minor allele (AC or AA genotype) reported significantly more drinking days (p = 0.045), significantly more frequent heavy episodic drinking (p = 0.003), and significantly higher alcohol-related problems and consumption patterns (AUDIT score p = 0.045, AUDIT-C score p = 0.02). Mediation analyses showed that the association of FAAH C385A with drinking outcomes was mediated by coping motives. CONCLUSIONS: These findings extend previous studies by suggesting that reduced endocannabinoid metabolism may be related to heavier use of alcohol in youth, prior to the onset of chronic drinking problems. Furthermore, differences in negative reinforcement-related drinking could account in part for this association.

Depression, Environmental Reward, Coping Motives and Alcohol Consumption During the COVID-19 Pandemic.

Background: Increases in the incidence of psychological distress and alcohol use during the COVID-19 pandemic have been predicted. Behavioral theories of depression and alcohol self-medication theories suggest that greater social/environmental constraints and increased psychological distress during COVID-19 could result in increases in depression and drinking to cope with negative affect. The current study had two goals: (1) to examine self-reported changes in alcohol use and related outcomes after the introduction of COVID-19 social distancing requirements, and; (2) to test hypothesized mediation models to explain individual differences in self-reported changes in depression and alcohol use during the early weeks of the COVID-19 pandemic. Methods: Participants (n = 833) were U.S. residents recruited for participation in a single online survey. The cross-sectional survey included questions assessing environmental reward, depression, COVID-19-related distress, drinking motives, and alcohol use outcomes. Outcomes were assessed via retrospective self-report for two timeframes in the single survey: the 30 days prior to state-mandated social distancing ("pre-social-distancing"), and the 30 days after the start of state-mandated social distancing ("post-social-distancing"). Results: Depression severity, coping motives, and some indices of alcohol consumption (e.g., frequency of binge drinking, and frequency of solitary drinking) were significantly greater post-social-distancing relative to pre-social-distancing. Conversely, environmental reward and other drinking motives (social, enhancement, and conformity) were significantly lower post-social distancing compared to pre-social-distancing. Behavioral economic indices (alcohol demand) were variable with regard to change. Mediation analyses suggested a significant indirect effect of reduced environmental reward with drinking quantity/frequency via increased depressive symptoms and coping motives, and a significant indirect effect of COVID-related distress with alcohol quantity/frequency via coping motives for drinking. Discussion: Results provide early cross-sectional evidence regarding the relation of environmental reward, depression, and COVID-19-related psychological distress with alcohol consumption and coping motives during the early weeks of the COVID-19 pandemic. Results are largely consistent with predictions from behavioral theories of depression and alcohol self-medication frameworks. Future research is needed to study prospective associations among these outcomes.

Randomized trial of working memory training as an adjunct to inpatient substance use disorder treatment.

Despite interest in computerized working memory training as a transdiagnostic intervention, little is known about its feasibility and efficacy in addiction treatment settings. This double-blind, randomized controlled trial examined the efficacy of working memory training for improving performance on standardized measures of executive function during inpatient substance use disorder treatment. Secondary outcomes included delay discounting, adherence to cognitive training, and posttreatment relapse. Adults (N = 110) entering inpatient alcohol or drug treatment were randomized to active (adaptive) or control (nonadaptive) training conditions, with up to 25 training sessions spanning inpatient and postdischarge phases. In generalized estimating equation (GEE) analyses, the experimental group showed relatively greater improvements on the primary outcome (digit span performance) based on Time × Treatment interactions in per-protocol (p < .05) and intent-to-treat (p = .07) models. Similar results were observed for one secondary outcome. Lower working memory performance at baseline predicted significantly greater delay discounting; however, no time or treatment effects on discounting were observed. Adherence to cognitive training was generally good during inpatient treatment, but suboptimal overall. These results suggest that implementing cognitive training is feasible in inpatient settings, and that adaptive working memory training can potentially lead to near-transfer effects for select cognitive outcomes. However, further work is necessary to establish training effects on clinical outcomes and to improve adherence in outpatient contexts. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data.

BACKGROUND: Differences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status. METHODS: To address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined. RESULTS: Our descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction. CONCLUSIONS: Evidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.

A prospective study of genetic factors, human laboratory phenotypes, and heavy drinking in late adolescence.

Subjective responses to alcohol are considered candidate endophenotypes for alcohol use disorder and appear to anticipate future consumption. However, prospective studies have been rare, and laboratory research has typically examined subjective responses absent measures of self-administration. This study examined the association of subjective responses with subsequent laboratory self-administration, also evaluating laboratory phenotypes in relation to putative genetic risk factors [family history (FH) of alcohol dependence and OPRM1 genotype] and subsequent heavy drinking. Participants (N = 61, M = 19.89 years, SD = 0.86) completed laboratory sessions involving intravenous alcohol challenge (Session 1) and free-access intravenous self-administration (Session 2), followed by prospective assessments. Multilevel modeling showed that higher reported stimulation and lower sedation during Session 1 independently predicted greater alcohol self-administration during Session 2. Although self-administration did not differ by FH group, participants with the OPRM1 118G allele evidenced steeper breath alcohol concentration (BrAC) trajectories and greater peak BrAC relative to 118A homozygous participants. Prospective analyses supported significant indirect associations between Session 1 subjective responses and 6-month heavy drinking via peak BrAC in Session 2. Additionally, significant indirect associations of FH (via Session 1 stimulation and Session 2 peak BrAC) and OPRM1 (via peak BrAC) with follow-up heavy drinking were observed. These results further support the utility of human laboratory phenotypes in prospective studies of alcohol use disorder risk and highlight the potential role of self-administration phenotypes in longitudinal research.