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BackgroundSeveral personality traits predict future alcohol problems but also relate to demographic and substance-related variables that themselves correlate with later adverse alcohol outcomes. Few prospective studies have evaluated whether personality measures predict alcohol problems after considering current demographic and substance-related variables.MethodsData from 414 drinkers without alcohol use disorder (AUD) from the Collaborative Study on the Genetics of Alcoholism (average age 20, 44% male) were followed over an average of 9 years. Time 1 (baseline) demography, AUD family history (FH), substance use and problems, and psychiatric histories were gathered using a standardized interview; the Level of Response (LR) to alcohol was measured by the Self-Report of the Effects of alcohol (SRE) questionnaire; and seven personality dimensions were extracted from the NEO Five-Factor Personality, Barratt, and Zuckerman scales. Analyses involved product-moment correlations of each baseline measure with the highest number of DSM-IV AUD criteria endorsed in any follow-up period, and hierarchical regression analyses evaluated whether the personality domains added significantly to the prediction of the outcome after adjusting for other baseline variables.ResultsSignificant correlations with the outcome were observed for baseline age, sex, length of follow-up, AUD family history, past cannabis use, and all alcohol-related baseline variables, including SRE-based LR, but not prior mood or anxiety disorders. All personality characteristics except extraversion also correlated with outcomes. A hierarchical regression analysis that included all relevant personality scores together demonstrated significant contributions to the prediction of future alcohol problems for demographics in Step 1; demographics and most baseline alcohol items, including response level, in Step 2; and cannabis use in Step 3; after which demographics, LR, baseline alcohol problems, cannabis use, and higher sensation seeking added significantly in Step 4. Regression for each personality domain separately revealed significant contributions to Step 4 for all personality domains except openness. Lower levels of response to alcohol added significantly to all regression analyses.ConclusionsMost tested personality scores and lower levels of response to alcohol contributed to predictions of later alcohol problems even after considering baseline demographic and substance use measures.

BackgroundEndorsement of specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) alcohol use disorder (AUD) criteria have been shown to change significantly over time in men in their thirties who have persistent or recurrent AUD. However, few studies have documented whether the endorsement of AUD items changes over time in younger individuals or in women. We evaluated changes in the endorsement of AUD criteria in 377 men and women with persistent or recurrent AUD during their twenties.MethodsInformation on AUD-item endorsement over time was available for 223 men and 154 women aged 20-25 with persistent or recurrent AUD in at least three interviews in the Collaborative Study on the Genetics of Alcoholism. The statistical significance of endorsement changes over time was evaluated using the related-sample Cochran's Q test for the full sample and for men and women separately. Additional analyses evaluated sex differences in the patterns of change.ResultsIn the full sample, the predominant pattern was for a significant increase in the rates of endorsement for six of the seven alcohol dependence criteria but not in the four abuse criteria. A similar pattern was seen within men, but women had significant changes in only three of the seven dependence criteria.ConclusionsEndorsement of the seven alcohol dependence criteria among individuals with persistent or recurrent AUD in their twenties generally increased, but few changes were observed in the rates of endorsement of the four abuse criteria. These results are discussed in terms of how they reflect on the nature of AUD and the DSM criteria.

BackgroundParents impact their offspring's brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1256, mean age [SD] = 19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring.MethodsSelf-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task.ResultsMultivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p = 0.002) and higher FT power (p = 0.01). Closeness with mother was associated with less binge drinking (p = 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father's and mothers' AUD symptoms, socioeconomic status, and offspring impulsivity in the model.ConclusionsAmong high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.

BackgroundHigh alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol.MethodsWe obtained information from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis.ResultsMortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer, 1.87 (1.61-2.17) for any circulatory disease, and 9.40 (7.00-12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment.ConclusionsPeople with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

BackgroundSubjective response (SR) to alcohol represents a biobehavioral risk factor for heavy drinking and for developing alcohol use disorder (AUD). Identifying moderators of SR have been hindered by small sample sizes that are often used in alcohol administration studies.MethodsThis study combined data from multiple alcohol administration trials to test whether sex, family history of alcohol problems, and impulsivity (via delay discounting) predict SR to alcohol, comprised of four domains: stimulation, sedation, negative affect, and craving. Non-treatment-seeking heavy drinkers (N = 250) completed a battery of self-report scales and behavioral measures of alcohol use and problems, mood, and impulsivity. All participants completed an intravenous alcohol administration session wherein SR domains were measured at baseline, 20, 40, and 60 mg%.ResultsAnalyses using multilevel modeling showed that male sex independently predicted higher alcohol-induced stimulation and alcohol craving, after controlling for other moderators. A family history of alcohol problems also independently predicted alcohol craving after controlling for other moderators.ConclusionsUsing a large sample and advanced data analytic methods, this study extends the literature on alcohol administration by identifying important moderators of SR in heavy drinkers: namely, male sex and family history of alcohol problems. These findings consolidate and extend a growing body of research aimed at differentiating individuals most likely to report the SR features that confer risk for AUD.

BackgroundEarly identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD.MethodsWe studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity.ResultsAUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ).ConclusionsBoth PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

BackgroundLong-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease.MethodsIn this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking.ResultsWe identified a list of up- and downregulated EV-miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased production of the inflammatory cytokines TNFα or IL-6 in peripheral blood mononuclear cells after stimulation.ConclusionThis exploratory study identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking and provide a mechanism to explain alcohol-induced peripheral inflammation.

BackgroundData from 2 generations of participants in the San Diego Prospective Study (SDPS) were used to compare cross-sectional and prospective relationships of 5 measures of the low level of response (low LR) to alcohol to 2 key alcohol-related outcomes.MethodsThe analyses used data from 373 SDPS male probands and 158 male and female offspring of these individuals to evaluate relationships of 5 LR measures to the prior 5-year maximum drinks per occasion and the number of 11 DSM-IV alcohol use disorder (AUD) criteria experienced. Probands' LR measures included responses to alcohol challenges administered 15 years previously, and ratings for both generations included measures of the number of standard drinks during four periods: the first five times of drinking (SRE-5), the prior three drinking months (SRE-3), the period of heaviest drinking (SRE-H), and a total average across all time frames (SRE-T). Analyses included zero-order correlations, correlations using covariates, and hierarchical multiple regression analyses.ResultsAll 5 LR measures were correlated with aspects of maximum drinks and the number of AUD criteria, but the most robust results were seen for SRE-3 and maximum drinks. Correlations were less consistent for SRE-5, a measure more closely related to outcomes in the offspring. Hierarchical regression analyses supported most of these conclusions and showed that alcohol challenge-based LRs added significant information regarding maximum drinks even when evaluated with SRE values. The close correlation between SRE-H and SRE-T argues against the need for studies to include both measures. The patterns of results were similar irrespective of whether covariates were included.ConclusionsThere were significant correlations of maximum drinks and the number of AUD criteria with findings from prior alcohol challenges and all SRE scores. Challenges and SRE reports are related but not identical LR measures. All SRE scores, including SRE-5, offered useful information regarding subsequent drinking behavior.

BackgroundDiagnostic and Statistical Manual (DSM) alcohol use disorder (AUD) criteria are written in broad enough terms to apply to diverse populations. The current analyses evaluate whether the endorsement of criteria changes with increasing age in individuals with persistent AUDs.MethodsData regarding AUDs persisting across 3 timepoints between average ages of 31 and 43 were gathered about every 5 years from 318 interviews for 106 San Diego Prospective Study (SDPS) AUD male probands. Similar data regarding persistent AUDs across 2 timepoints were obtained from 136 interviews with 68 SDPS AUD offspring between average ages of 21 and 27. Changes in the endorsement of each AUD criterion were evaluated using Cochran's Q test.ResultsFor AUD probands across time, significant decreases were observed in the proportions endorsing 4 criteria (tolerance, withdrawal, failure to fulfill obligations, and using alcohol in hazardous situations). Increased rates of endorsement were documented for 3 criteria (drinking alcohol in higher amounts or for longer periods of time, spending a great deal of time regarding alcohol, and continued use despite social or interpersonal problems). Significant increases in rates of endorsements for offspring were seen for spending a great deal of time regarding alcohol and giving up or reducing important activities in order to drink.ConclusionsThese data indicate that the salience of many DSM AUD criterion items changed significantly with age in both SDPS generations among individuals with persistent AUDs. The current results support the need for additional systematic research to determine whether specific criterion items might need to be weighted differently in evaluating older and younger individuals with persistent AUDs.

In this narrative review, we present the hypothesis that key mutations in two genes, occurring 15 and 10 million years ago (MYA), were individually and then collectively adaptive for ancestral humans during periods of starvation, but are maladaptive in modern civilization (i.e., "thrifty genes"), with the consequence that these genes not only increase our risk today for obesity, but also for alcoholism. Both mutations occurred when ancestral apes were experiencing loss of fruit availability during periods of profound climate change or environmental upheaval. The silencing of uricase (urate oxidase) activity 15 MYA enhanced survival by increasing the ability for fructose present in dwindling fruit to be stored as fat, a consequence of enhanced uric acid production during fructose metabolism that stimulated lipogenesis and blocked fatty acid oxidation. Likewise, a mutation in class IV alcohol dehydrogenase ~10 MYA resulted in a remarkable 40-fold increase in the capacity to oxidize ethanol (EtOH), which allowed our ancestors to ingest fallen, fermenting fruit. In turn, the EtOH ingested could activate aldose reductase that stimulates the conversion of glucose to fructose, while uric acid produced during EtOH metabolism could further enhance fructose production and metabolism. By aiding survival, these mutations would have allowed our ancestors to generate more fat, primarily from fructose, to survive changing habitats due to the Middle Miocene disruption and also during the late-Miocene aridification of East Africa. Unfortunately, the enhanced ability to metabolize and utilize EtOH may now be acting to increase our risk for alcoholism, which may be yet another consequence of once-adaptive thrifty genes.

BackgroundFew studies have investigated the partner's influence on risk factors such as alcohol consumption and depression during pregnancy. Partner substance use and lower relationship satisfaction predict higher maternal alcohol use and depressive symptoms. Because prenatal alcohol use and maternal depression affect infant outcomes, it is imperative to examine how the partner affects these maternal risk factors. The current study examined the effect of a latent construct of partner influence on maternal alcohol use and depressive symptoms, and the effects on infant development of these maternal factors.MethodsParticipants were 246 pregnant women from 2 sites in Western Ukraine from whom longitudinal data were collected as part of a multisite study. In the first trimester, mothers reported on relationship satisfaction, partner substance use, and socioeconomic status (SES). In the third trimester, they reported on alcohol use and depressive symptoms. Infants were assessed using the Bayley Scale of Infant Development (average age = 6.93 months). A latent construct titled partner influence was formed using partner substance use and measures of relationship satisfaction, including the frequency of quarreling, happiness in the relationship, and the ease of talking with the partner. Using structural equation modeling, a model was specified in which partner influence and SES predicted maternal alcohol use and depressive symptoms, which in turn predicted infant neurodevelopmental outcomes.ResultsHigher partner influence significantly predicted lower prenatal alcohol use and lower depressive symptoms, controlling for the effect of SES. Higher maternal prenatal alcohol use significantly predicted lower infant mental and psychomotor development. Maternal depressive symptoms did not predict infant development over and above the effect of alcohol use.ConclusionsPartner influence is an important contributor to prenatal alcohol use and maternal depressive symptoms, over and above the effect of SES. The significant paths from prenatal alcohol exposure to infant neurodevelopmental outcomes underscore the importance of partner influence during pregnancy.

BackgroundPrenatal alcohol exposure (PAE) has been identified as one of the leading preventable causes of developmental disabilities, but early identification of those impacted has been challenging. This study evaluated the use of infant cardiac orienting responses (CORs), which assess neurophysiological encoding of environmental events and are sensitive to the impact of PAE, to predict later fetal alcohol spectrum disorder (FASD) status.MethodsMother-infant dyads from Ukraine were recruited during pregnancy based on the mother's use of alcohol. Participants (n = 120) were then seen at 6 and 12 months when CORs were collected and in the preschool period when they were categorized as having (i) fetal alcohol syndrome (FAS), (ii) partial FAS (pFAS), (iii) alcohol-related neurodevelopmental disorder (ARND), (iv) PAE and no diagnosis, or (v) no PAE and no diagnosis. To assess CORs, stimuli (auditory tones and pictures) were presented using a fixed-trial habituation/dishabituation paradigm. Heart rate (HR) responses were aggregated across the first 3 habituation and dishabituation trials and converted to z-scores relative to the sample's mean response at each second by stimuli. Z-scores greater than 1 were then counted by condition (habituation or dishabituation) to compute a total risk index.ResultsSignificant group differences were found on total deviation scores of the CORs elicited from visual but not auditory stimuli. Those categorized as pFAS/FAS had significantly higher total deviation scores than did those categorized as ARND or as having no alcohol-related diagnosis with or without a history of PAE. Receiver operating characteristic curve analysis of the visual response yielded an area under the curve value of 0.765 for predicting to pFAS/FAS status.ConclusionsA score reflecting total deviation from typical HR during CORs elicited using visual stimuli in infancy may be useful in identifying individuals who need early intervention as a result of their PAE.

BackgroundDirect biomarkers such as phosphatidylethanol (PEth) have the capability to detect heavy alcohol use, but it is unclear how strongly self-reported reduction in alcohol use correlates with reduction in PEth. We sought to explore the strength of correlation between reductions in self-reported alcohol use and change in PEth among a sample of women living with HIV (WLWH) who participated in a clinical trial to reduce heavy alcohol use. We also sought to determine whether this correlation was stronger in women with lower body mass index (BMI) and women without an alcohol use disorder (AUD).Methods81 WLWH (mean age = 48.7, 80% Black) engaging in a randomized trial of naltrexone versus placebo with a positive baseline PEth (≥8 ng/ml), and alcohol use data at baseline, 2, and 7 months were included in this analysis. Spearman correlation coefficients were compared to measure the correlation between baseline PEth and number of drinks per week by demographic, biological, and alcohol use factors. Mini-International Neuropsychiatric Interview was used to screen for AUD. Further analyses were stratified by BMI and AUD. Spearman correlation coefficients were calculated for the change in PEth and the change in number of drinks per week over 7 months, including 3 time-points: baseline, 2, and 7 months.ResultsAt baseline, the correlation between baseline PEth and the number of drinks per week was significantly stronger for those with a BMI ≤25 compared to those with a BMI > 25 (r = 0.66; r = 0.26, respectively). Similarly, the correlation between baseline PEth and number of drinks was stronger for those who did not screen positive for AUD compared with those who did (r = 0.66; r = 0.25, respectively). When stratifying by BMI, a low-to-moderate correlation (r = 0.32, p = 0.02) was present for persons with a BMI > 25; when stratifying by AUD, a moderate correlation (r = 0.50, p

BackgroundAlcohol use disorder (AUD) is heterogenous. One approach to parsing this heterogeneity is to phenotype individuals by their underlying motivation to drink, specifically drinking for reward (i.e., positive reinforcement) or for relief (i.e., negative reinforcement/normalizing). Reward- versus relief-motivated behavior is thought to be associated with a shift from ventral to dorsal striatal (DS) signaling. The present study examined whether reward and relief drinking were differentially associated with other clinical characteristics and with alcohol cue-elicited activation of the ventral and dorsal striatum.MethodsNon-treatment-seeking heavy drinkers (N = 184; 61 female, 123 male) completed the UCLA Reward, Relief, Habit Drinking Scale (RRHDS) and the Reasons for Heavy Drinking Questionnaire (RHDQ), to categorize drinking motivation. Measures of alcohol use, alcohol problems, mood, and craving were also collected. A subset of participants (N = 45; 17 female, 28 male) also completed a functional neuroimaging alcohol cue reactivity task.ResultsRRHDS-designated relief/habit drinkers scored lower than reward drinkers on the RHDQ Reinforcement subscale (p = 0.04) and higher on the RHDQ Normalizing subscale (p = 0.004). Relief/habit drinkers also demonstrated greater AUD severity on a host of clinical measures. Relief/habit drinkers displayed higher cue-elicited DS activation compared with reward drinkers (p = 0.04), while ventral striatal cue-elicited activation did not significantly differ between groups.ConclusionsOur findings support and extend the differentiation of reward from relief/habit-motivated drinking and suggest that differences in DS response to conditioned alcohol cues may underlie this distinction. Elucidating neurobiological and clinical differences between these subtypes may facilitate treatment matching and precision medicine for AUD.

BackgroundIn animal models, it is possible to induce different alcohol-related dysmorphic abnormalities based on the timing of prenatal alcohol exposure (PAE). Our objective was to assess whether patterns of PAE differentially predict alcohol-related dysmorphic features in 415 infants.MethodsWe analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. Five distinct trajectories were previously identified to summarize PAE: (i) minimal/no PAE (n = 253), (ii) low/moderate PAE with reduction early in gestation (n = 78), (iii) low/moderate sustained PAE (n = 20), (iv) moderate/high PAE with reduction early in gestation (n = 45), and (v) high sustained PAE (n = 19). A dysmorphology examination of body size, 3 cardinal, and 15 noncardinal dysmorphic features was performed at approximately 6 to 12 months of age. A modified dysmorphology score was created based on previously published weights. Univariate comparisons were made between each dysmorphic feature and trajectory group. Features that differed by trajectory group were assessed in multivariable analyses. Models were adjusted for maternal age, prenatal vitamin use, socioeconomic status, smoking, and child's age at dysmorphology examination, with censoring weights for losses to follow-up.ResultsThe 3 highest trajectories predicted total dysmorphology score, with larger effects in sustained exposure groups. Cardinal features: The 3 highest trajectories were each associated with a 2- to 3-fold increased risk of having 2 + cardinal facial features. When assessed individually, there were no consistent associations between the individual trajectories and each cardinal feature. Noncardinal features: The 3 highest trajectories were associated with increased risk of hypotelorism. Only the highest trajectory was associated with heart murmur. The highest trajectory predicted

BackgroundThe most efficient approach for establishing family histories (FHs) asks informants about disorders in their relatives (a Family History Method [FHM]). However, FHMs underestimate family diagnoses. We evaluated if accuracies of young adult offspring report of their father's alcohol use disorders (AUDs) related to the age, sex, education, and/or substance-related patterns/problems of either the young adult informants or their AUD fathers.MethodsData from the San Diego Prospective Study (SDPS), a multigenerational 35-year investigation, compared father/offspring pairs where the proband father's alcohol problems were correctly (Group 1) or incorrectly (Group 2) noted by offspring. In the key analysis, Group 1 versus 2 results were entered into bootstrapped backward logistic regression analyses predicting Group 1 membership.ResultsFive proband and one offspring characteristic were associated with correct identification of their father's alcohol problems. None of these related to age, education, or sex. Characteristics associated with correct FHM diagnoses included the father's FH of AUDs, self-report of drinking despite social/interpersonal or physical/psychological alcohol-related problems, spending much time related to alcohol, and his having a religious preference. The single offspring item predicting correct identification of the father's problems was the number of DSM alcohol problems of the offspring.ConclusionsIn the SDPS, FHM sensitivity was most closely related to the father's drinking characteristics, not the offspring characteristics. While unique aspects of SDPS families potentially limit generalizability of results, the data demonstrate how the FHM can offer important initial steps in the search for genetically related AUD risks in a subset of families.

BackgroundThe effects of prenatal alcohol exposure (PAE) are conceptualized as fetal alcohol spectrum disorder, with fetal alcohol syndrome (FAS) as the most severe. Many find it more difficult to characterize behavioral and cognitive effects of exposure on the central nervous system when physical signs are not present. In the current study, an operational definition of alcohol-related neurodevelopmental disorder (ARND) was examined to determine its usefulness in discrimination of children classified as ARND based on behavior (ARND/B) and cognition (ARND/C) from children in 4 contrast groups: (i) children exposed to study-defined "risky drinking"; (ii) children with any reported PAE; (iii) children classified as "Higher Risk" for developmental problems; and (iv) children classified as "Lower Risk."MethodsA total of 1,842 children seen as part of a surveillance study (J Am Med Assoc, 319, 2018, 474) were evaluated for alcohol exposure and physical characteristics of FAS, and completed neurodevelopmental testing. Ninety-one were identified as either ARND/B or ARND/C and contrasted with other groups to further identify distinguishing patterns. Multinomial logistic regression (MLR) was used to examine the accuracy of classification and to identify factors contributing to such classification.ResultsChildren described as ARND/C were distinct from other groups based on cognition and behavior as well as demographic factors (e.g., age, race, SES), child characteristics (e.g., gestational age; sex), and other drug exposures, while those described as ARND/B differed only on behavior and other drug exposures. MLR models successfully discriminated ARND groups from children in other groups with accuracy ranging from 79% (Higher Risk) to 86.7% (Low Risk).ConclusionsARND has been a subject of debate. This analysis suggests the effects of alcohol on behavior and cognition even in the absence of the characteristic facial features and growth deficiency that can be identified. The results also indicate that it may be possible to distinguish such children from those in other high-risk groups.

BackgroundFamily history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD.MethodsData from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM-5 AUD diagnostic information obtained through direct interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM-5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes.ResultsDensity measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude.ConclusionsDensity (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD.

BackgroundCerebellar atrophy (especially involving the superior-anterior cerebellar vermis) is among the most salient and clinically significant effects of chronic hazardous alcohol consumption on brain structure. Smaller cerebellar volumes are also associated with chronic cigarette smoking. The present study investigated effects of both chronic alcohol consumption and cigarette smoking on cerebellar structure and its relation to performance on select cognitive/behavioral tasks.MethodsUsing T1-weighted Magnetic Resonance Images (MRIs), the Cerebellar Analysis Tool Kit segmented the cerebellum into bilateral hemispheres and 3 vermis parcels from 4 participant groups: smoking (s) and nonsmoking (ns) abstinent alcohol-dependent treatment seekers (ALC) and controls (CON) (i.e., sALC, nsALC, sCON, and nsCON). Cognitive and behavioral data were also obtained.ResultsWe found detrimental effects of chronic drinking on all cerebellar structural measures in ALC participants, with largest reductions seen in vermis areas. Furthermore, both smoking groups had smaller volumes of cerebellar hemispheres but not vermis areas compared to their nonsmoking counterparts. In exploratory analyses, smaller cerebellar volumes were related to lower measures of intelligence. In sCON, but not sALC, greater smoking severity was related to smaller cerebellar volume and smaller superior-anterior vermis area. In sALC, greater abstinence duration was associated with larger cerebellar and superior-anterior vermis areas, suggesting some recovery with abstinence.ConclusionsOur results show that both smoking and alcohol status are associated with smaller cerebellar structural measurements, with vermal areas more vulnerable to chronic alcohol consumption and less affected by chronic smoking. These morphometric cerebellar deficits were also associated with lower intelligence and related to duration of abstinence in sALC only.

BackgroundSelf-report is widely used to assess alcohol use in research and clinical practice, but may be subject to social desirability bias. We aimed to determine if social desirability impacts self-reported alcohol use.MethodsAmong 751 human immunodeficiency virus (HIV)-infected patients from a clinic in southwestern Uganda, we measured social desirability using the Marlowe-Crowne Social Desirability Scale (SDS) Short Form C, self-reported alcohol use (prior 3 months) Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and phosphatidylethanol (PEth), a biomarker of prior 3 weeks' drinking. We conducted multiple regression analyses to assess the relationship between SDS score (low, medium, and high levels) and (i) any self-reported recent alcohol use, among those who were PEth-positive (≥8 ng/ml), and (ii) continuous AUDIT-C score, among those reporting any recent alcohol use. We controlled for PEth level, age, gender, education, economic assets, marital status, religion, spirituality/religiosity, social support, and study cohort.ResultsOf 751 participants, 59% were women; the median age was 31 years (interquartile range [IQR]: 26 to 39). Median SDS score was 9 (IQR: 4 to 10). Two-thirds (62%) self-reported any recent alcohol use; median AUDIT-C was 1 (IQR: 0 to 4). Among those who were PEth-positive (57%), 13% reported no recent alcohol use. Those with the highest SDS tertile had decreased odds of reporting any recent alcohol use compared to the lowest tertile, but the association did not reach statistical significance in multivariable analyses (adjusted odds ratio 0.55 [95% confidence interval (CI): 0.25, 1.23]). Among participants self-reporting recent alcohol use, SDS level was negatively associated with AUDIT-C scores (adjusted β: -0.70 [95% CI: -1.19, -0.21] for medium vs. low SDS and -1.42 [95% CI: -2.05, -0.78] for high vs. low SDS).ConclusionsWhile use of objective measures (e.g., alcohol biomarkers) is desirable for measuring alcohol use, SDS scores may be used to adjust self-reported drinking levels by participants' level of social desirability in HIV research studies.

IntroductionBehavioral economic theory views addiction as a reinforcer pathology characterized by excessive demand for drugs relative to alternatives. Complementary to this theory, Lamb and Ginsburg (Pharmacology Biochemistry and Behavior, 164, 2018, 62) describe addiction as a behavioral allocation disorder and predict that decisions to drink under increasingly stringent constraints are a central indicator of addiction. This study used a modified demand-curve paradigm to examine alcohol demand in the context of a next-day contingency (high opportunity cost demand) as a specific indicator of a severe pattern of alcohol problems.MethodsParticipants were 370 undergraduates (61.1% female, 86.5% white, Mage  = 18.8) reporting multiple past-month heavy drinking episodes (5/4 drinks per occasion for men/women) who completed 2 versions of an alcohol purchase task (APT), along with measures of past-month alcohol use and problems. In 1 APT (low opportunity cost), students imagined they had no next-day responsibilities, and in the other APT (high opportunity cost), they imagined having a 10:00 am test the next day. Item-response theory analyses were used to determine mild and severe alcohol problems from the Young Adult Alcohol Consequences Questionnaire (Journal of Studies on Alcohol, 67, 2006, 169), and the most and least severe binge drinking days throughout the week.ResultsLow opportunity cost demand (β = 0.15, p = 0.02) significantly predicted beyond high opportunity cost demand for the least severe problems, and high opportunity cost demand (β = 0.17, p = 0.009) significantly predicted beyond low opportunity cost demand for the most severe problems. Similarly, low opportunity cost demand (β = 0.26, p

BACKGROUND:There are limited data on the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers from the general population in the United States. METHODS:During the 2012 and 2013 academic years, first-grade children in a large urban Pacific Southwest city were invited to participate in a study to estimate the prevalence of FASD. Children who screened positive on weight, height, or head circumference ≤25th centile or on parental report of developmental concerns were selected for evaluation, along with a random sample of those who screened negative. These children were examined for dysmorphology and neurobehavior and their mothers or collateral sources were interviewed. Children were classified as fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), or No FASD. RESULTS:A total of 854 children were evaluated; 5 FAS, 44 pFAS, 44 ARND, and 761 No FASD. Children with FAS or pFAS were more likely to have dysmorphic features, and 32/49 (65.3%) of those met criteria for neurobehavioral impairment on cognitive measures with or without behavioral deficits. In contrast, 28/44 (63.6%) of children with ARND met criteria on behavioral measures alone. Mothers of FASD children were more likely to recognize pregnancy later, be unmarried, and report other substance use or psychiatric disorders, but did not differ on age, socioeconomic status, education, or parity. Mothers of FASD children reported more drinks/drinking day each trimester. The risk of FASD was elevated with increasing number of drinks/drinking day prior to pregnancy recognition, even at the level of 1 drink per day (adjusted odds ratio 3.802, 95% confidence interval 1.634, 8.374). CONCLUSIONS:Data from this general population sample in a large urban region in the United States demonstrate the variability of expression of FASD and point to risk and protective factors for mothers in this setting.

BackgroundThe levels of the ω-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with alcohol sensitivity in vertebrate and invertebrate model systems, but prior studies have not examined this association in human samples despite evidence of associations between ω-3 LC-PUFA levels and alcohol-related phenotypes. Both alcohol sensitivity and ω-3 LC-PUFA levels are impacted by genetic factors, and these influences may contribute to observed associations between phenotypes. Given the potential for using EPA and DHA supplementation in adjuvant care for alcohol misuse and other outcomes, it is important to clarify how ω-3 LC-PUFA levels relate to alcohol sensitivity.MethodsAnalyses were conducted using data from the Avon Longitudinal Study of Parents and Children. Plasma ω-3 LC-PUFA levels were measured at ages 15.5 and 17.5. Participants reported on their initial alcohol sensitivity using the early drinking Self-Rating of the Effects of Alcohol (SRE-5) scale, for which more drinks needed for effects indicates lower levels of response per drink, at ages 15.5, 16.5, and 17.5. Polygenic liability for alcohol consumption, alcohol problems, EPA levels, and DHA levels was derived using summary statistics from large, publicly available datasets. Linear regressions were used to examine the cross-sectional and longitudinal associations between ω-3 LC-PUFA levels and SRE scores.ResultsAge 15.5 ω-3 LC-PUFA levels were negatively associated with contemporaneous SRE scores and with age 17.5 SRE scores. One modest association (p = 0.02) between polygenic liability and SRE scores was observed, between alcohol problems-based polygenic risk scores (PRS) and age 16.5 SRE scores. Tests of moderation by genetic liability were not warranted.ConclusionsPlasma ω-3 LC-PUFA levels may be related to initial sensitivity to alcohol during adolescence. These data indicate that diet-related factors have the potential to impact humans' earliest responses to alcohol exposure.

BackgroundCognitive-behavioral therapy (CBT) has long-standing evidence for efficacy in the treatment of alcohol use, yet implementation in clinical practice has been challenging. Delivery of CBT through technology-based platforms, such as web-based programs and mobile applications, has the potential to provide widespread access to this evidence-based intervention. While there have been reviews indicating the efficacy of technology-based delivery of CBT for various psychiatric conditions, none have focused on efficacy for alcohol use. The current meta-analysis was conducted to fill this research gap.MethodsDescriptive data were used to characterize the nature of the literature on technology-delivered, CBT-based interventions for alcohol use ("CBT Tech"). Inverse-variance-weighted effect sizes were calculated, and random effects, effect sizes were pooled in 4 subgroups.ResultsFifteen published trials conducted primarily with at-risk or heavy drinkers were identified. Of these studies, 60% explicitly targeted alcohol use moderation. The content of CBT Tech programs varied, ranging from 4 to 62 sessions/exercises, with many programs combining elements of motivational interviewing (47%). With respect to efficacy, CBT Tech as a stand-alone treatment in contrast to a minimal treatment control showed a positive and statistically significant, albeit small effect (g = 0.20: 95% CI = 0.22, 0.38, kes  = 5). When CBT Tech was compared to treatment as usual (TAU), effects were nonsignificant. However, when CBT Tech was tested as an addition to TAU, in contrast to TAU only, the effect size was positive, significant (g = 0.30: 95% CI = 0.10, 0.50, kes  = 7), and stable over 12-month follow-up. Only 2 studies compared CBT Tech to in-person CBT, and this pooled effect size did not suggest superior efficacy.ConclusionsThese results show a benefit for technology-delivered, CBT-based interventions as a stand-alone therapy for heavy drinking or as an addition to usual care in specialty substance use settings.

BackgroundThe 35-year-long San Diego Prospective Study documented 2-fold increases in alcohol problems and alcohol use disorders (AUDs) in young-adult drinking offspring compared to rates in their fathers, the original probands. The current analyses use the same interviews and questionnaires at about the same age in members of the 2 generations to explore multiple potential contributors to the generational differences in adverse alcohol outcomes.MethodsUsing data from recent offspring interviews, multiple cross-generation differences in characteristics potentially related to alcohol problems were evaluated in 3 steps: first through direct comparisons across probands and offspring at about age 30; second by backward linear regression analyses of predictors of alcohol problems within each generation; and finally third through R-based bootstrapped linear regressions of differences in alcohol problems in randomly matched probands and offspring.ResultsThe analyses across the analytical approaches revealed 3 consistent predictors of higher alcohol problems in the second generation. These included the following: (i) a more robust relationship to alcohol problems for offspring with a low level of response to alcohol; (ii) higher offspring values for alcohol expectancies; and (iii) higher offspring impulsivity.ConclusionsThe availability of data across generations offered a unique perspective for studying characteristics that may have contributed to a general finding in the literature of substantial increases in alcohol problems and AUDs in recent generations. If replicated, these results could suggest approaches to be used by parents, healthcare workers, insurance companies, and industry in their efforts to mitigate the increasing rates of alcohol problems in younger generations.

Alcohol use disorder (AUD) is a chronic relapsing condition that represents a significant public health concern. Pharmacological treatment development for AUD is a top research priority, and many studies are being conducted to evaluate potential AUD treatments. Understanding the brain circuitry impacted by addiction is crucial for the development of efficacious pharmacological interventions. These neuroadaptations can be probed noninvasively using functional magnetic resonance neuroimaging (fMRI). fMRI may be an effective tool to identify biomarkers for AUD pharmacotherapies, evaluating changes associated with pharmacological treatment. Thus, the present qualitative review of the literature focuses on the role of fMRI as a tool for medication development for AUD. The aim of this review was to assemble research across a range of fMRI paradigms to study the effectiveness of pharmacological treatments of adult AUD. First, we present a qualitative review of fMRI AUD pharmacotherapy studies, differentiating studies based on their dosing regimen. Second, we provide recommendations for the field to improve the use of fMRI as a biomarker for AUD pharmacotherapy.

BackgroundWe have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis.MethodsWe conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate-to-high levels of alcohol or low/unexposed controls, (ii) children with PAE and non-alcohol-exposed controls, and (iii) children with PAE treated with or without choline.ResultsWe found pregnant women who consumed moderate-to-high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE.ConclusionsThese data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.

BackgroundAlcohol consumption and problems are increasing among older adults, who are at elevated risk for alcohol-related accidents and medical problems. This paper describes a pilot follow-up of older adults with a history of alcohol dependence that was designed to determine the feasibility of conducting a more extensive investigation.MethodsThe sample consisted of previously assessed subjects in the Collaborative Studies on the Genetics of Alcoholism who: (i) were age 50+; (ii) had lifetime DSM-IV AD; and (iii) had DNA available. Individuals were located through family contacts, Internet searches, and death registries. A brief telephone interview assessed demographics, health, and alcohol involvement.ResultsOf the total sample (N = 2,174), 36% were contacted, 24% were deceased, and 40% were not yet located. Most (89%) contacted subjects were interviewed, and 99% of them agreed to future evaluation. Thirty percent of interviewed subjects reported abstinence for 10+ years, 56% reported drinking within the past year, and 14% last drank between >1 and 10 years ago. There were no age-related past-year differences in weekly consumption (overall sample mean: 16 drinks), number of drinking weeks (30.8), maximum number of drinks in 24 hours (8.1), or prevalence of weekly risky drinking (19%). Among those who drank within the past 5 years, the 3 most common alcohol-related problems were spending excessive time drinking or recovering (49%), drinking more/longer than intended (35%), and driving while intoxicated (35%); and about a third (32%) received some form of treatment.ConclusionsOver a 1-year period, we located 60% of individuals last seen an average of 23 years ago. The majority of contacted individuals were interviewed and willing to be evaluated again. Although the proportion of individuals currently drinking diminished with age, subjects exhibited troublesome levels of alcohol consumption and problems. Our findings suggest the importance and feasibility of a more comprehensive follow-up.

It has been known for over 4 decades that prenatal alcohol exposure (PAE) can adversely affect neurodevelopment and behavior (NDB). Yet, early detection of altered NDB due to PAE continues to present a major clinical challenge. Identification of altered NDB in the first 2 years of life, before higher-order cognitive processes develop, invites early interventions for affected children to improve long-term outcomes. Studies published in English from January of 1980 to July of 2018 were identified in PubMed/MEDLINE. The review focused on prospective birth cohort studies which used standardized NDB assessments in children up to 2 years of age, wherein PAE was the main exposure and NDB was the main outcome. NDB was categorized into the domains of neurocognitive, adaptive, and self-regulation based on the 2016 Updated Clinical Guidelines for Diagnosing fetal alcohol spectrum disorder. An initial search resulted in 1,867 articles for which we reviewed abstracts; 114 were selected for full-text review; and 3 additional abstracts were identified through review of references in eligible publications. Thirty-one publications met criteria and were included: of these, 24 reported neurocognitive outcomes, 24 reported adaptive behavior outcomes, and 12 reported outcomes in the domain of self-regulation. Although self-regulation was assessed in the fewest number of studies, 8/12 (75%) reported PAE-associated deficits. In contrast, results were mixed for the other 2 domains: 13/24 (54%) of the selected studies that included neurocognitive outcomes showed poorer performance following PAE, and 8/24 (33%) studies that assessed adaptive functioning found significant differences between PAE and comparison infants. There is considerable evidence to support the value of early-life assessments of infant NDB when PAE is known or suspected. More studies focusing on infant self-regulation, in particular, are needed to determine the utility of early evaluation of this critical developmental domain in infants with PAE.

BACKGROUND:Low level of responses (low LRs) to alcohol established using the Self-Report of the Effects of Alcohol (SRE) questionnaire are genetically influenced phenotypes related to heavy drinking and alcohol problems. To date, most studies using SREs focused on scores for the number of drinks needed for effects across the first 5 times of drinking (SRE-5), and few evaluated scores that also included the prior 3 months and heaviest drinking periods (SRE-T). This paper evaluates characteristics of SRE-5 and SRE-T within and across generations. METHODS:Data were extracted from 407 participants across 2 generations of 107 families in the San Diego Prospective Study (SDPS). Pearson's product-moment correlations for SRE-5 and SRE-T were determined across first-degree relatives both within and across generations and sexes, as well as correlations of each measure to maximum drinking quantities and alcohol problems. RESULTS:Responding to 4 hypotheses, first the analyses demonstrated significant within-generation positive correlations for both SRE measures across brother-brother and sister-sister pairs as well as cross-generation correlations for fathers and sons, although correlations for mothers and daughters were not robust. Second, both SRE-5 and SRE-T correlated with maximum drinks and alcohol problems for both sexes and both generations. Third, within parental and offspring generations SRE-T correlated more robustly than SRE-5 to maximum drinks and alcohol problems. Fourth, across generations SRE values for sons were more closely related to drinking quantities and problems than for their fathers, but the mother-daughter SRE relationships to adverse alcohol characteristics were not different. CONCLUSIONS:Both the SRE-5 and SRE-T offered useful information about propensities toward heavier drinking and alcohol problems in SDPS families. Correlations with adverse alcohol outcomes were greater for the more broad-based SRE-T, but both scores appeared to be genetically influenced and continue to operate in a robust manner in both generations of these families.

BackgroundAlcohol-induced blackouts, a form of anterograde amnesia that restricts the encoding of short-term memories into long-term ones, are among the most severe alcohol-related consequences. College students are at high risk of experiencing alcohol-induced blackouts, and there is a need to determine whether alcohol interventions can effectively reduce blackouts in this population. The current study uses data from 3 randomized clinical trials to examine the effect of various intervention approaches on alcohol-induced blackouts.MethodsFour interventions were compared over 3 studies: (i) a computerized feedback intervention (electronic Check-Up To Go [e-Chug]; Study 1); (ii) a single-session brief motivational intervention (BMI; Study 1); (iii) a BMI plus behavioral economic session focused on increasing substance-free activities (BMI + Substance-Free Activity Session [SFAS]; Studies 2 and 3); and (iv) a BMI plus supplemental Relaxation Training session (BMI + Relaxation Training; Studies 2 and 3). Studies 1 and 3 also included an assessment-only control condition. For each study, participants reported whether they had experienced an alcohol-induced blackout at each time point; binary logistic regressions examined differential likelihood of experiencing an alcohol-induced blackout over time.ResultsNeither the single-session BMI nor e-Chug reduced alcohol-induced blackouts over assessment only; however, participants in the BMI + SFAS or BMI + Relaxation Training condition were significantly less likely to experience an alcohol-induced blackout compared to assessment only at 1-month (Wald = 4.77, odds ratio [OR] = 0.53, p = 0.03) and 6-month follow-ups (Wald = 5.72, OR = 0.52, p = 0.02). Study 2 also revealed a larger effect for the BMI + SFAS over the BMI + Relaxation Training condition at 6 months (Wald = 4.11 OR = 0.22, p = 0.043), although this was not replicated in Study 3. The effects for the 2-session BMIs lasted 6 months, at which point maturation effects diminished differences between assessment-only and intervention conditions.ConclusionsTwo sessions of BMI are a substantial enough dose to result in reductions in alcohol-induced blackouts among college student heavy drinkers.

BackgroundPrevious studies indicate that low initial sensitivity to alcohol may be a risk factor for later alcohol misuse. Evidence suggests that initial sensitivity is influenced by genetic factors, but few molecular genetic studies have been reported.MethodsWe conducted a meta-analysis of 2 population-based genome-wide association studies of the Self-Rating of the Effects of Alcohol scale. Our final sample consisted of 7,339 individuals (82.3% of European descent; 59.2% female) who reported having used alcohol at least 5 times. In addition, we estimated single nucleotide polymorphism (SNP)-based heritability and conducted a series of secondary aggregate genetic analyses.ResultsNo individual locus reached genome-wide significance. Gene and set based analyses, both overall and using tissue-specific expression data, yielded largely null results, and genes previously implicated in alcohol problems and consumption were overall not associated with initial sensitivity. Only 1 gene set, related to hormone signaling and including core clock genes, survived correction for multiple testing. A meta-analysis of SNP-based heritability resulted in a modest estimate of hSNP2  = 0.19 (SE = 0.10), though this was driven by 1 sample (N = 3,683, hSNP2  = 0.36, SE = 0.14, p = 0.04). No significant genetic correlations with other relevant outcomes were observed.ConclusionsFindings yielded only modest support for a genetic component underlying initial alcohol sensitivity. Results suggest that its biological underpinnings may diverge somewhat from that of other alcohol outcomes and may be related to core clock genes or other aspects of hormone signaling. Larger samples, ideally of prospectively assessed samples, are likely necessary to improve gene identification efforts and confirm the current findings.

BackgroundRecent reports indicate higher-than-expected problematic drinking in older populations. However, few data describe how to predict which older individuals are most likely to demonstrate alcohol-related problems, including those with earlier alcohol use disorders (AUDs). These analyses evaluate predictors of alcohol outcomes in individuals with earlier AUDs in the Collaborative Study on Genetics of Alcoholism (COGA).MethodsOriginal COGA participants with baseline AUDs at about age 40 were interviewed 13 to 26 years later and placed into clinically derived outcome categories. Chi-square and analysis of variance evaluated baseline differences across 4 outcome groups, with significant items entered into binary logistic regression backwards elimination analyses predicting outcomes.ResultsLow-Risk Drinkers (N = 100) at follow-up were predicted by baseline higher levels of response to alcohol (high LRs), lower histories of alcohol treatment, experience with fewer types of illicit drugs, and were more likely to have been widowed. At follow-up, Problem Drinkers (N = 192) differed from High-Risk Drinkers (N = 93) who denied multiple alcohol problems by exhibiting baseline lower LRs, higher Sensation Seeking, and a higher proportion who were widowed. Abstinent (N = 278) outcomes were predicted by a history of higher baseline AUD treatments, higher alcohol problems, lower usual drinks, as well as older age and European American heritage. Thirty-four subjects (4.9%) could not be classified and were not included in these analyses.ConclusionsThese results generated from AUD individuals from both treatment and nontreatment settings reinforce low probabilities of recent Low-Risk Drinking in individuals with AUDs, but also suggest many individuals with AUDs demonstrate good outcomes 2 decades later.

BackgroundPregaming is a common, high-risk drinking activity among college students that has been largely unchangeable despite targeted intervention approaches. Therefore, identifying profiles of pregamers could enhance understanding of the risks associated with this practice and inform intervention development.MethodsThis study identified subtypes of pregamers in undergraduates (N = 911; 60% female, 42.9% White) attending 3 U.S. universities in 2012. Self-report data assessed recent alcohol use (overall, heavy, and pregaming), pregaming motives, and demographics. Alcohol-related consequences were assessed via the Young Adult Alcohol Consequences Questionnaire.ResultsLatent profile analysis using pregaming-specific indicators assessing motives (e.g., to avoid getting caught) and consumption (e.g., estimated pregaming blood alcohol concentration) yielded 5 unique profiles. Three profiles were characterized by pregaming on 50% or more of all drinking events that differed by pregaming consumption and motives: Instrumental (5.3%; heavy consumption, intoxication-driven motives), Global (16.0%; moderate consumption, indistinct motives), and Risk-averse (18.3%; moderate-to-heavy consumption, negatively reinforcing motives). Two profiles reported lower levels of pregaming: Occasional (32.4%; moderate consumption, indistinct motives) and Infrequent (28.0%; lowest pregaming involvement). Cross-profile differences were then examined for demographics, general drinking and pregaming-specific motives, and alcohol-related consequences. Profile comparisons indicated differences in overall alcohol consumption, ethnicity, gender, current living arrangements, Greek involvement, and a variety of alcohol-related consequences (ps

BACKGROUND:Widespread brain atrophy in alcohol-dependent individuals (ALC) has been consistently documented in pathological and magnetic resonance imaging (MRI) studies. Longitudinal MRI studies have shown that the regional brain volume losses in ALC are partially reversible during abstinence from alcohol. The goal of this study was to determine volume reductions in cortical and subcortical regions functionally important to substance use behavior and their changes during short-term (1 week to 1 month) and long-term abstinence (1 to 7 months) from alcohol. The regions of interest (ROIs) were as follows: anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), insula, amygdala, and hippocampus. METHODS:A total of 85 unique ALC were assessed at 1 week (n = 65), 1 month (n = 82), and 7 months (n = 36) of abstinence. In addition, 17 light/nondrinking healthy controls (CON) were assessed at baseline and follow-up over a 10-month interval. Regional brain volumes were derived from FreeSurfer. Cross-sectional statistical analyses using 1-way analysis of variance or Fisher's exact test were applied to identify group differences. Longitudinal statistical analyses using linear mixed models were applied to identify regional volume increases and nonlinear volume recovery trajectories. RESULTS:We demonstrated significant regional volume reductions in ACC, DLPFC, and hippocampus. Older age was associated with smaller DLPFC and OFC, and higher average monthly drinking over 1 year prior to study was associated with smaller OFC. We also demonstrated significant volume increases of all ROIs except amygdala in ALC and significant nonlinear volume recovery trajectories of DLPFC, OFC, and insula. CONCLUSIONS:Results showed significant volume reductions in key regions of the executive control, salience, and emotion networks in ALC at entry into treatment and significant volume increases during short-term and long-term abstinence that were nonlinear over the entire abstinence period for the DLPFC, OFC, and insula. This gray matter plasticity during alcohol abstinence may have important neurobiological and neurocognitive implications in ALC, and it may contribute to an individual's ability to maintain abstinence from alcohol at different phases.

BackgroundOur aim was to describe alcohol consumption trajectories in a cohort of people living with HIV and determine clinical and sociodemographic predictors of each trajectory.MethodsThis 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.ResultsWe 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.ConclusionsLongitudinal trajectories of increasing alcohol use and stable misuse highlight the need to integrate routine screening and alcohol misuse interventions into HIV primary care.

BackgroundPhosphatidylethanol (PEth) is a direct biomarker for alcohol that is formed shortly after alcohol use and may remain detectable in blood for weeks after alcohol consumption. There is little research on alcohol use factors that influence PEth elimination, especially among women.MethodsData were collected from 116 alcohol use-disordered women who were recently incarcerated. We used a 2-part model with logistic and linear components to examine whether alcohol consumption in the 2 weeks prior to incarceration and days since last alcoholic drink (operationalized as abstinence days prior to incarceration + days incarcerated) were associated with PEth detectability (>8 ng/ml) and level (ng/ml) in blood.ResultsParticipants reported drinking an average of 10 drinks per day in the 2 weeks prior to incarceration. Days since last drink was negatively associated with PEth level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.93; 0.99) and being PEth detectable (OR = 0.96, 95% CI = 0.91; 0.99). Quantity of alcohol consumed prior to jail admission was associated with PEth detection (OR = 1.08; 95% CI = 1.03; 1.16), but not PEth level.ConclusionsDays since last alcoholic drink and drinks per day both influenced PEth detectability, but only days since last drink predicted PEth level among a large sample of women with alcohol use disorder in the criminal justice system.

BackgroundBiomarkers can play a key role in supplementing self-report information in alcohol research. In this study, we examined phosphatidylethanol (PEth) in comparison with self-reported alcohol use over time in a randomized controlled trial.MethodsParticipants were women living with HIV enrolled in a randomized placebo-controlled trial of naltrexone for reducing hazardous drinking. Drinking behavior was measured using Timeline Followback (TLFB), and PEth as a biomarker using dried blood spots. Data collected at baseline, and months 2 and 7 were analyzed. In addition to calculated Spearman's correlations, mixed-effects modeling was used to evaluate the changes in self-reported drinking and PEth, respectively, adjusting for body mass index (BMI).ResultsA total of 194 participants (83% black, mean age 48) were included in the analysis. PEth levels were significantly correlated with self-reported drinking via TLFB, Spearman's r = 0.21 at baseline, r = 0.29 at 2 months, and r = 0.28 at 7 months, respectively. No demographic or health factors, except for BMI, was associated with whether self-report was consistent with PEth. Mixed-effects model indicated that self-reported drinking showed significantly greater reductions in the naltrexone treatment group than the placebo group at the 2- and 7-month visits, whereas PEth measure only showed this difference at the 7-month follow-up.ConclusionsThe magnitude of the correlation between PEth and self-reported alcohol consumption was small. Caution is needed when using either self-report or PEth as a sole outcome measure for alcohol behavior changes in clinical trials.

BackgroundTreatment for alcohol use disorders (AUDs) has traditionally been abstinence oriented, but new research and regulatory guidelines suggest that low-risk drinking may also be an acceptable treatment outcome. However, little is known about long-term outcomes for patients who become low-risk drinkers posttreatment. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and psychosocial outcomes over 9 years.MethodsStudy participants were adults with AUDs at treatment entry who received follow-up interviews 6 months posttreatment intake (N = 1,061) in 2 large randomized studies conducted at Kaiser Permanente Northern California, a large private, nonprofit, integrated health system. Six-month drinking status was defined as abstinent, low-risk (nonabstinent, no 5+ drinking days), or heavy drinking (1 or more days of 5+ drinks). Using logistic regression models, we explored the relationship between past 30-day drinking status at 6 months and odds of being abstinent or a low-risk drinker (compared to heavy drinking), and positive Addiction Severity Index psychosocial outcomes over 9 years (9-year follow-up rate of 73%).ResultsAbstainers and low-risk drinkers at 6 months had higher odds of recent abstinence/low-risk drinking over 9 years than heavy drinkers; abstainers had better drinking outcomes than low-risk drinkers. Additionally, among those with interview data, 95% of abstainers and 94% of low-risk drinkers at 6 months were abstinent/low-risk drinkers at 9 years; surprisingly, 89% of heavy drinkers at 6 months were also abstinent/low-risk drinkers although still significantly fewer than the other groups. Abstainers and low-risk drinkers at 6 months had better psychiatric outcomes, and abstainers had better family/social outcomes than heavy drinkers; medical outcomes did not differ. Low-risk drinkers and abstainers showed no reliable differences across psychosocial measures.ConclusionsThe findings suggest that a low-risk drinking outcome may be reasonable over the long-term for some alcohol-dependent individuals receiving addiction treatment.

BackgroundAll stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear whether the same factors are associated consistently across early and late transitions in AUD involvement. High-risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development.MethodsData from adolescents and young adults from high-risk families were used to study 4 transitions in AUD development-time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures, and internalizing and externalizing psychopathology across transitions.ResultsHazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders, and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Nonassaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition.ConclusionsIn this large, ethnically diverse sample of high-risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the United States, the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.

BackgroundRelapse in alcohol use disorders (AUD) is related to a complex interplay among multiple biological, psychiatric, psychological, and psychosocial factors, which may change dynamically during and after treatment. At treatment entry for AUD, morphological abnormalities in anterior frontal regions and the insula have been observed in those who ultimately relapse following treatment. The goal of this study was to determine whether anterior frontal and insula measures of brain thickness, surface area, and volume predict posttreatment drinking status (i.e., relapser or abstainer) over an extended period after outpatient treatment for AUD, while concurrently considering common psychiatric, psychological, and psychosocial factors previously associated with relapse.MethodsAlcohol-dependent individuals (n = 129) were followed for 18 months after treatment to determine posttreatment drinking status (abstainers [n = 47] or relapsers [n = 82]). Brain morphometrics were derived from FreeSurfer. Receiver operating characteristic (ROC) curve analysis was used to identify the regional brain thickness, surface area, and volume (all scaled to intracranial volume), demographic, psychiatric, other substance use (e.g., cigarette smoking), and alcohol consumption variables, obtained at entry into treatment, that best predicted posttreatment drinking status. Survival analyses determined variables that were related to duration of abstinence after treatment.ResultsROC analyses indicated that mood disorders, education, and volumes of the right caudal anterior cingulate cortex (ACC), right rostral ACC, and total right frontal gray matter were significant predictors of posttreatment drinking status. Among relapsers, survival analyses showed smokers and individuals with a comorbid medical condition relapsed earlier after treatment. Additionally, a greater frequency of smokers relapsed within 6 months of AUD treatment.ConclusionsResults reinforce that relapse in AUD is a function of multiple biological, psychiatric, psychological, and psychosocial factors. Effective treatment of depressive disorders and cigarette smoking concurrent with AUD-focused interventions may promote better treatment outcomes.

BackgroundReward deprivation has been implicated in major depressive disorder and severe substance abuse, but its potential relation to alcohol use disorder (AUD) symptoms in non-treatment-seeking young adult drinkers is less clear. Depression is often comorbid with alcohol misuse, so relations of AUD with reward deprivation might be due in part to the presence of depressive symptoms in young adults. Behavioral economic theory views addiction as a state that is related in part to deficits in drug-free rewards, and therefore requires an investigation into whether reward deprivation has a direct relation to alcohol misuse that is, at least partially, independent of mood.MethodsThis study evaluates the contribution of 2 facets of reward deprivation (reward availability and experience) to alcohol use, AUD symptoms, and depression in a sample of young adult heavy episodic drinkers. Data were collected from 392 undergraduates (60.4% female, 85.1% Caucasian) who reported recent heavy drinking (83.7% with at least 1 AUD symptom).ResultsLow reward availability (environmental suppression) was significantly associated with both DSM-5 AUD symptoms and alcohol-related problems after controlling for age, gender, depressive symptomatology, and drinking level.ConclusionsThis study provides support for behavioral economic models that emphasize reward deprivation as a unique risk factor for AUD that is independent of mood and drinking level. Limited access to natural rewards may be a risk and/or maintaining factor for AUD symptoms in college student drinkers.

BackgroundEarly detection of fetal alcohol spectrum disorders (FASDs) is desirable to allow earlier and more comprehensive interventions to be initiated for the mother and infant. We examined prenatal ultrasound as an early method of detecting markers of the physical features and neurobehavioral deficits characteristic of FASD.MethodsA longitudinal cohort of pregnant women in Ukraine was recruited as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Women were enrolled into a moderately to heavy-alcohol-exposed group or a low- or no-alcohol exposure group and were followed to pregnancy outcome. In the second trimester, a fetal ultrasound was performed to measure transverse cerebellar diameter, occipital frontal diameter (OFD), caval-calvarial distance, frontothalamic distance (FTD), interorbital distance (IOD), outer orbital diameter, and orbital diameter (OD). Live born infants received a dysmorphological examination and a neurobehavioral evaluation using the Bayley Scales of Infant Development. These data were used to classify infants with respect to FASD. Comparisons were made on the ultrasound measures between those with and without features of FASD, adjusting for gestational age at ultrasound and maternal smoking.ResultsA total of 233 mother/child dyads were included. Children classified as FASD had significantly longer IOD and lower FTD/IOD, OFD/IOD, and FTD/OD ratios (p

BackgroundPrenatal alcohol exposure (PAE) has been found to impact neurophysiological encoding of environmental events negatively in the first year of life but has not been evaluated in older infants or toddlers. Cardiac orienting responses (ORs) collected during a habituation/dishabituation learning paradigm were obtained from 12- to 18-month-olds to assess the impact of PAE beyond the first year of life.MethodsParticipants included women and their toddlers who differed in PAE histories and enrolled in a randomized clinical trial of multivitamin/mineral usage during pregnancy. Those who were randomly assigned to the no intervention group were used for this analysis. The habituation/dishabituation paradigm consisted of 10 habituation and 5 dishabituation trials. Baseline heart rate (HR) was collected for 30 seconds prior to stimulus onset, and responses to the stimuli were assessed by sampling HR for 12 seconds poststimulus onset.ResultsThe speed of the OR in response to auditory stimuli in the dishabituation condition was found to be altered as a function of maternal alcohol use around conception. For visual stimuli, positive histories of PAE were predictive of the magnitude but not the speed of the response on habituation and dishabituation trials. A history of binge drinking was associated with reduced magnitude of the OR response on visual encoding trials, and level of alcohol exposure at the time of conception was predictive of the magnitude of the response on visual dishabituation trials.ConclusionsCardiac ORs collected in the toddler period were sensitive to the effects of PAE. The magnitude of the OR was more sensitive to the impact of PAE than in previous research with younger infants, and this may be a function of brain maturation. Additional research assessing the predictive utility of using ORs in making decisions about individual risk was recommended.

Alcohol use is common among people living with human immunodeficiency virus (HIV). In this narrative review, we describe literature regarding alcohol's impact on transmission, care, coinfections, and comorbidities that are common among people living with HIV (PLWH), as well as literature regarding interventions to address alcohol use and its influences among PLWH. This narrative review identifies alcohol use as a risk factor for HIV transmission, as well as a factor impacting the clinical manifestations and management of HIV. Alcohol use appears to have additive and potentially synergistic effects on common HIV-related comorbidities. We find that interventions to modify drinking and improve HIV-related risks and outcomes have had limited success to date, and we recommend research in several areas. Consistent with Office of AIDS Research/National Institutes of Health priorities, we suggest research to better understand how and at what levels alcohol influences comorbid conditions among PLWH, to elucidate the mechanisms by which alcohol use is impacting comorbidities, and to understand whether decreases in alcohol use improve HIV-relevant outcomes. This should include studies regarding whether state-of-the-art medications used to treat common coinfections are safe for PLWH who drink alcohol. We recommend that future research among PLWH include validated self-report measures of alcohol use and/or biological measurements, ideally both. Additionally, subgroup variation in associations should be identified to ensure that the risks of particularly vulnerable populations are understood. This body of research should serve as a foundation for a next generation of intervention studies to address alcohol use from transmission to treatment of HIV. Intervention studies should inform implementation efforts to improve provision of alcohol-related interventions and treatments for PLWH in healthcare settings. By making further progress on understanding how alcohol use affects PLWH in the era of HIV as a chronic condition, this research should inform how we can mitigate transmission, achieve viral suppression, and avoid exacerbating common comorbidities of HIV and alcohol use and make progress toward the 90-90-90 goals for engagement in the HIV treatment cascade.

BackgroundChildren exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored.MethodsSixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit.ResultsAlcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance.ConclusionsAlthough results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.

BackgroundHeavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Although current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large-scale evaluation (Schuckit et al., , ) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state-of-the-art (SOTA) standard prevention program for individuals with the low LR risk factor.MethodsThis study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of 4 weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a 6-month period.ResultsIndividuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between LR and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g., maximum drinks, frequency of heavy drinking) than high LR individuals.ConclusionsThese results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions. Long-term follow-ups and further investigations of tailored prevention programs based on other risk factors are needed.

BackgroundSubjective responses (SRs) to alcohol have been implicated in alcoholism etiology, yet less is known about the latent factor structure of alcohol responses. The aim of this study was to examine the factor structure of SR using a battery of self-report measures during a controlled alcohol challenge.MethodsNontreatment seeking drinkers (N = 242) completed an intravenous alcohol challenge including the following SR measures: Biphasic Alcohol Effects Scale, Subjective High Assessment Scale, Profile of Mood States, Alcohol Urge Questionnaire, and single items assessing alcohol "Liking" and "Wanting." Ascending limb target breath alcohol concentrations were 0.02, 0.04, and 0.06, and descending limb target was 0.04 g/dl. Exploratory factor analyses were conducted separately on estimates of mean and dose responses on the ascending limb and on descending limb data. To examine the generalizability of this factor structure, these analyses were repeated in heavy drinkers (≥14 drinks/wk for men, ≥7 for women; n = 132) and light drinkers (i.e., nonheavy drinkers; n = 110).ResultsIn the full sample, a 4-factor solution was supported for ascending limb mean and dose responses and descending limb data representing the following SR domains: Stimulation/Hedonia, Craving/Motivation, Sedation/Motor Intoxication, and Negative Affect. This 4-factor solution was replicated in heavy drinkers. In light drinkers, however, SR was better summarized by a 3-factor solution where ascending mean and descending limb responses consisted of Stimulation/Hedonia, Craving/Motivation, and a general negative valence factor, and dose responses consisted of a general positive valence factor, Sedation/Motor Intoxication, and Negative Affect.ConclusionsThese findings suggest that SR represents a multifaceted construct with consistent factor structure across both ascending and descending limbs. Further, as drinking levels escalate, more defined Craving/Motivation and negative valence dimensions may emerge. Longitudinal studies examining these constructs are needed to further our understanding of SR as potentially sensitive to alcohol-induced neuroadaptation.

BackgroundThe risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS).MethodsThe GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected.ResultsWe have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055).ConclusionsRecruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

BackgroundMultiple forms of anxiety psychopathology are associated with alcohol use problems in adolescents. Yet, the mechanisms underlying this association are unclear. Anxiety sensitivity (AS) and distress tolerance (DT) represent 2 distinct, conceptually relevant transdiagnostic constructs implicated in multiple manifestations of anxiety that may also underlie alcohol use problems and thereby explain why people with anxiety are more likely to have alcohol problems.MethodsThe current cross-sectional study examined whether AS and DT accounted for (i.e., statistically mediated) the relationship between manifest indicators of the 3 common anxiety phenotypes (generalized anxiety, social anxiety, and panic disorders) and alcohol problems in a sample of 534 high school students (14 to 15 years old).ResultsMultiple manifestations of anxiety were associated with greater alcohol use problems. AS statistically mediated multiple anxiety-alcohol associations, but DT did not.ConclusionsThese findings provide preliminary evidence suggesting AS may be an important transdiagnostic target for alcohol prevention programs for those in early adolescence that experience elevated anxiety symptoms.