Wiley: Alcohol, Clinical and Experimental Research: Table of Contents

Using Routinely Collected Data From the Network of Alcohol and Other Drugs Agencies Database to Evaluate the Impact of COVID‐19 Lockdowns on Trends in Service Delivery in Outpatient Non‐Government Alcohol and Other Drug Treatment Services

Fri, 10 Apr 2026 23:00:15 -0700

This observational study used routinely collected data from community-based, non-government alcohol, and other drug services in New South Wales, Australia. Lockdown measures did not adversely impact the number of treatment episodes that commenced or increased the likelihood of unplanned dropout. These findings highlight the sector's resilience and capacity to sustain care through rapid service adaptation.

ABSTRACT

Background

The COVID-19 pandemic disrupted face-to-face alcohol and other drug (AOD) treatment services and prompted greater use of telehealth. This study measured the impact of COVID-19 on outpatient treatment episodes before, during, and after stay-at-home orders were introduced.

Methods

This observational study used routinely collected data from community-based non-government AOD services in New South Wales (NSW), Australia across 4 years (209 7-day intervals from January 1, 2019–January 2, 2023). Interrupted time-series analyses with seasonal autoregressive integrated moving average (ARIMA) modeling estimated weekly changes in outpatient treatment episodes associated with stay-at-home (lockdown) orders, including (1) commencements, (2) planned cessations, and (3) unplanned cessations. Episode counts were also examined by gender (male, female), age group (< 25 years, 25–59 years, ≥ 60 years), principal drug of concern (alcohol, amphetamines, cannabinoids, opioids, and other), and location (metropolitan and non-metropolitan).

Results

There were no significant level or trend changes in the overall number of episode commencements (ARIMA (2,0,0)(1,0,0), lockdown one: β_level = −814.85, p = 0.098; β_slope = 11.14, p = 0.127; lockdown two: β_level = 317.3, p = 0.427; β_slope = −3.47, p = 0.237), planned cessations (ARIMA (1,0,0)(0,0,1), lockdown one: β_level = −142.1, p = 0.66; β_slope = 1.16, p = 0.808; lockdown two: β_level = −199.07, p = 0.432; β_slope = 0.18, p = 0.932), or unplanned cessations (ARIMA (1,0,0), lockdown one: β_level = −92.4, p = 0.717; β_slope = 1.4, p = 0.711; lockdown two: β_level = −121.19, p = 0.563; β_slope = 0.53, p = 0.732) in outpatient non-government AOD services at either lockdown. For subgroups, during lockdown one, commencements per week increased for metropolitan participants (ARIMA (1,0,0) β_level = −725.12, p = 0.024; β_slope = 10.07, p = 0.035) and those with amphetamines (ARIMA(3,0,0)(1,0,0) β_level = −338.44, p = 0.036; β_slope = 4.68, p = 0.05) as their principal drug of concern.

Conclusions

The introduction of COVID-19 lockdown measures did not appear to adversely impact the number of NSW non-government AOD outpatient treatment episodes delivered nor the likelihood of unplanned dropout. Our findings illustrate the likely role of telehealth in sustaining (and for some groups, perhaps temporarily increasing) AOD service provision during the COVID-19 pandemic. This highlights the sector's resilience in sustaining care under challenging circumstances.

Participant Demographic and Baseline Drinking Factors Can Predict Alcohol Use Disorder Pharmacotherapy Clinical Trial Completion and Drinking Outcomes

Michaela Hoffman, Raymond F. Anton, Arnie Aldridge — Thu, 09 Apr 2026 23:04:33 -0700

Five multisite AUD pharmacotherapy trial data were merged to explore participant prestudy characteristics as outcome predictors. Pre-randomization “days since last drink” significantly predicted three drinking outcomes. Further analyses suggested that more than 3–5 days of consecutive abstinence would reduce chances of finding a significant medication effect, secondary to increased placebo response.

ABSTRACT

Background

Partially due to the complexity associated with conducting trials, there have been relatively few regulatory agency-approved medications for the treatment of alcohol use disorder (AUD). Heterogeneity of study samples, such as participant characteristics (including variation in alcohol consumption) as well as drinking efficacy endpoints, may lead to inconsistency in results and a potential increase in Type II errors. The aim of this study is to begin to fill in the knowledge gap of optimal clinical trial design by analyzing potential predictors of outcomes.

Methods

Five federally funded and publicly available multisite randomized pharmacotherapy clinical trials for the treatment of AUD using similar methodologies to assess drinking outcomes were included. Three FDA-guided drinking efficacy outcomes were calculated for each study independently and combined: abstinence (no drinking days), no heavy drinking days, WHO 2+ risk drinking level (RDL) reduction as well as a measure of study participant completion. These outcomes were analyzed by logistic regression models including a variety of predictors within the full-study sample as well as among only participants treated with placebo.

Results

The number of days abstinent prior to randomization was a strong positive predictor of all three predefined drinking outcomes. Further analysis indicated a cutoff of less than three to five abstinent days before randomization might be optimal. For the WHO 2+ RDL endpoint, those within the “high” or “very-high” risk categories were more likely to meet criteria for successful two or more risk level reductions than “medium” risk. Across various demographic variables, only age (older participants) was associated with better outcomes.

Conclusions

These findings suggest that some important prestudy drinking characteristics (e.g., less abstinence and older age) as well as being in a higher risk drinking category should be considered for inclusion in future alcohol pharmacotherapy trials.

Factors associated with alcohol abstinence in North American Indigenous youth: Age, gender, and cultural identity

Thu, 09 Apr 2026 00:05:48 -0700

This study examines reasons North American Indigenous youth abstain from alcohol use and whether these reasons mediate the relationship between cultural identity and future drinking intentions. Social reasons, but not negative consequences, mediated this relationship after controlling for contextual factors. These findings extend evidence of cultural identity's protective role and suggest that fostering social reasons for abstaining from alcohol may be a modifiable target to promote alcohol abstinence among Indigenous youth.

Abstract

Background

North American Indigenous youth are at increased risk for alcohol use, yet little literature explores why some choose to abstain from alcohol use. This study aimed to: characterize the reasons why Indigenous youth abstain from alcohol; explore how these reasons vary by age, sex, and whether or not the youth reside on or off a reservation; and examine how reasons for abstaining may mediate the relationship between cultural identity and intentions to drink 5 years in the future.

Methods

Data were sourced from the Substance Use Among American Indian Youth: Epidemiology and Etiology, [United States], 2015–2020 study. Data from 2665 Indigenous youth (48.1% female, M _age = 14.2 (SD = 1.7)) who reported no lifetime alcohol use were extracted.

Results

Factor analysis of the reasons for abstaining from alcohol resulted in two factors: to avoid negative consequences and due to social reasons. Females (vs. males), younger (vs. older) youth, and youth who lived on a reservation (vs. those who did not) endorsed avoiding consequences and social reasons as more important (p's < 0.01). A serial mediation analysis found that, while controlling for age, sex, and reservation-dwelling, social, but not negative consequences, reasons significantly mediated the relationship between cultural identity and intention to drink 5 years in the future (indirect effect = −0.020, p = 0.02, 95% CI [−0.039, −0.005]).

Conclusions

These results extend previous research on the protective role of cultural identity on alcohol use and suggest that developing social reasons to abstain from alcohol may be a modifiable risk factor to encourage alcohol abstinence in Indigenous youth.

Acute Ethanol Significantly Enhances GABAergic Transmission in the Central Lateral Amygdala of Alcohol‐Naïve and Alcohol‐Dependent Male Rats

Emaya M. Moss, Enkhzul Batsaikhan, Samantha Amsden, Dean Kirson — Tue, 07 Apr 2026 22:21:56 -0700

Acute alcohol produces sex-specific effects on GABAergic transmission in the lateral central amygdala (CeL), enhancing inhibitory signaling in males but not females. This is the first electrophysiological study focused specifically on the CeL to characterize inhibitory neurotransmission under both alcohol-naïve and alcohol-dependent conditions. This underscores the importance of including both sexes in alcohol research, as understanding the mechanisms underlying these differences may inform the development of sex-specific treatments for alcohol use disorder.

ABSTRACT

Background

The central nucleus of the amygdala (CeA), a key component of the extended amygdala, is critical for mediating behavioral and physiological responses to stress and alcohol exposure. While extensive research has characterized alcohol's effects on GABAergic transmission in the medial CeA (CeM), the lateral CeA (CeL) remains underexplored, despite its central role in upstream signaling within the CeA circuit.

Methods

In this study, we examined the effects of acute ethanol (EtOH) on GABAergic transmission in the CeL of alcohol-naïve and alcohol-dependent male and female Wistar rats. Alcohol dependence was induced using a chronic intermittent ethanol vapor exposure protocol. Whole-cell patch-clamp recordings were conducted on CeL neurons to measure spontaneous inhibitory postsynaptic currents (sIPSCs) at baseline and following acute application of 44 mM EtOH.

Results

Acute EtOH significantly increased sIPSC frequency in CeL neurons from male rats, regardless of alcohol history, indicating enhanced presynaptic GABA release. In contrast, female rats showed no significant changes in sIPSC frequency or amplitude following acute EtOH application, whether alcohol-naïve or dependent. Several neuronal properties—including membrane resistance, holding current, and rheobase—were significantly altered in alcohol-dependent females. However, overall spiking characteristics and baseline inhibitory transmission did not differ significantly between naïve and dependent groups within each sex.

Conclusions

These findings reveal, for the first time, that acute EtOH produces sex-specific effects on GABAergic transmission in the CeL, enhancing inhibitory signaling in males but not females. This pattern mirrors previous observations in the CeM and underscores the importance of including both sexes in alcohol research. Understanding the mechanisms underlying these differences may inform the development of sex-specific treatments for alcohol use disorder.

Predictors of Breath Alcohol Profiles: A Multiple‐Study Lab‐Based Approach

Tue, 07 Apr 2026 22:02:34 -0700

Three profiles of breath alcohol content (BrAC) trajectories were observed across two oral alcohol administration studies: high-fast risers, moderate risers, and low-slow risers. BrAC profiles were also predicted by body mass index, total body water, and responses to alcohol.

ABSTRACT

Background

Oral alcohol administration studies often show a range of breath alcohol content (BrAC) following alcohol ingestion, though examination of BrAC trajectories as distinct profiles has yet to be explored as well as potential predictors of these profiles.

Methods

Across two laboratory studies of oral alcohol administration with target blood alcohol concentrations (BACs) of 0.08% (N = 89) and 0.10% (N = 92) of emerging adults (M _age = 23.03) with a history of binge drinking, BrAC was captured every 15 min for seven intervals. Repeated measure latent profile analysis (RMLPA) was used to determine latent profiles of BrAC based on Akaike information criterion (AIC), Bayesian information criterion (BIC), and the bootstrapped likelihood ratio test (BLRT) for each study. Individual characteristics and prior alcohol use history were then examined as predictors of latent profile membership for the 0.10% BrAC study.

Results

A three-profile solution was replicated across the 0.08% and 0.10% BAC emerging adult samples, consisting of (1) high-fast risers (10%–16%) where individuals reach higher than anticipated BrAC and maintain high levels across the study period, (2) moderate risers (35%–42%) who reach target BrAC levels and show expected rise and fall in BrAC, and (3) low-slow risers (46%–47%) who remain under target BrAC and show consistent low levels of BrAC across the study period. Body mass index, total body water, and response to alcohol assisted in predicting individual membership in the 0.10% BrAC study and can aid in differentiating profiles.

Conclusion

BrAC profiles for emerging adult samples may follow a three-profile structure during lab-based oral alcohol administration. One's physical characteristics and response to alcohol may play a key role in differentiating BAC profiles and should be examined in the lab and natural environment.

Associations of Low‐Level Prenatal Alcohol and Cannabis Exposure With Adolescent Cognitive Trajectories

Tue, 07 Apr 2026 21:59:39 -0700

Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents' cognitive development after accounting for sociodemographic factors. Families with social features positively associated with cognitive ability (e.g., education) may engage in low level drinking during pregnancy with few negative consequences on offspring cognition.

ABSTRACT

Background

No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.

Methods

N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (M _age = 9.95), two-year follow-up (M _age = 11.95), and four-year follow-up (M _age = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.

Results

Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.

Conclusions

Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents' cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.

Impact of Visual Masking on Attentional Bias in Cross‐Sectional Clinical and Healthy Populations: Differences in Conscious and Unconscious Processing of Alcohol‐Related Cues

Isabella Fuchs‐Leitner, Kurosch Yazdi‐Zorn, Jan Rosenleitner — Mon, 06 Apr 2026 21:33:42 -0700

This study examined how individuals with alcohol use disorder and healthy controls respond to alcohol-related cues, using masked and unmasked presentations to explore attentional biases and the role of cue awareness in cognitive processes related to craving and addiction.

ABSTRACT

Background

Attentional bias (AB) toward substance-related cues is a core cognitive mechanism in alcohol use disorder (AUD) and closely associated with craving and relapse risk. Yet, the extent to which AB reflects automatic bottom-up processes remains unclear.

Methods

This study (N = 107) examined alcohol-related AB in clinical populations (inpatients and outpatients with AUD) and healthy controls (occasional and non-drinkers). Alcohol cues were presented under masked and unmasked conditions in a dot-probe task, and AB was measured via reaction times. Patients also reported alcohol craving and dependence levels. The study assessed whether AB patterns differed between clinical and healthy groups, whether cue awareness modulated attentional processing, and whether alcohol-type preference within the clinical sample influenced AB. Finally, associations between craving, dependence, and AB were explored.

Results

As predicted, unmasked alcohol cues elicited significant AB in both inpatient and outpatient groups, but not in healthy controls. No significant AB emerged in masked trials for any subgroup, suggesting that alcohol-related AB is not fully automatic but depends on conscious awareness. Patients reporting current craving showed greater AB than those without craving. However, AB magnitude did not correlate with craving intensity, AUD severity scores, or alcohol-type preference.

Conclusions

These findings indicate that alcohol-related AB in AUD is shaped by conscious processing rather than purely automatic mechanisms, underscoring the role of top-down factors in attentional processes relevant to addiction.

Aquaporin 9 regulates acetaldehyde uptake, alcohol‐induced liver injury, and drinking behavior

Mon, 06 Apr 2026 08:00:05 -0700

We identify AQP9 as a regulator of acetaldehyde (AcH) influx into hepatocytes, coordinating hepatic and systemic AcH clearance. AQP9 deficiency mitigates early ALD while bidirectionally modulating alcohol consumption, revealing AQP9-regulated AcH transport as a determinant of alcohol metabolism, drinking behavior, and liver injury.

Abstract

Background

Acetaldehyde (AcH), a highly reactive metabolite of ethanol, plays a pivotal role in the pathogenesis of alcohol-associated liver disease (ALD) and alcohol use disorder (AUD). Post alcohol consumption, AcH generated in hepatocytes is further metabolized into acetate by aldehyde dehydrogenase 2 (ALDH2) or excreted into circulation and bile via the basolateral and apical membranes, respectively. Our previous studies have demonstrated that aquaporin 8 (AQP8), which is a water channel and mainly expressed on the apical membrane, facilitates AcH excretion into bile. AQP9 is predominantly expressed on the basolateral membrane of hepatocytes; however, the roles of AQP9 in AcH relocation and pathogenesis of ALD and AUD remain unknown.

Methods

AQP9 expression was examined in human ALD liver samples. The role of AQP9 was investigated by using the NIAAA mouse model of ALD, voluntary and binge-drinking behavior paradigms, global Aqp9 knockout (KO) mice, in situ liver perfusion, and primary hepatocyte culture assays.

Results

Our data demonstrated that hepatic AQP9 expression was markedly downregulated in ALD patients and correlated with liver injury markers and metabolic gene expression. In mice, Aqp9 KO ameliorated early-stage ALD by reducing hepatic lipogenesis, lipid peroxidation, and inflammation. In vivo and in vitro experiments revealed that AQP9 promotes AcH influx into hepatocytes. By using drinking in the dark experiments, we found that Aqp9 KO mice had reduced binge-like alcohol consumption compared with wild-type mice, while two-bottle choice experiments revealed that Aqp9 KO mice had slightly higher alcohol preference compared with wild-type mice.

Conclusions

Our findings suggest that AQP9 promotes hepatocytes to take up AcH, thereby exacerbating ALD progression and regulating alcohol-drinking behavior.

Assessment of early return to drinking in surviving patients with alcohol‐associated hepatitis

Mon, 06 Apr 2026 08:00:04 -0700

Among survivors of alcohol-associated hepatitis, nearly one-third resumed drinking within 6 months. High baseline drinking frequency and lower educational attainment independently predicted relapse, highlighting a critical window for early, structured addiction-focused interventions.

Abstract

Background

Recurrent alcohol use is a major determinant of liver-related outcomes in patients recovering from alcohol-associated hepatitis (AH). However, the timing and predictors of return to drinking (RTD) are not well-studied.

Methods

We analyzed alcohol use among patients with AH enrolled in two AlcHepNet multicenter studies: a Phase 2b randomized controlled trial and a prospective observational study. TimeLine FollowBack (TLFB) assessed drinking at each visit. RTD was defined as any alcohol use since the previous visit. The cumulative incidence of RTD was evaluated using the Fine–Gray method, with death as a competing risk. Factors associated with RTD were evaluated using univariate and multivariate Cox regression.

Results

Among 518 patients alive at Day 28, RTD occurred in 7.7%, 21.7%, and 30.8% at 30, 90, and 180 days, respectively. Patients with moderate AH (mAH, MELD 11–19, n = 103) had a higher RTD incidence at 180 days than those with severe AH (sAH, MELD ≥20, n = 415) (44.3% vs. 27.5%; p = 0.01). RTD was associated with higher AUDIT scores, family history of alcohol use disorder (AUD), lower education, greater alcohol use at baseline, lower MELD scores, and less ascites (all p ≤ 0.01). In multivariable analysis, >20 drinking days in the prior month was associated with increased risk of RTD (HR: 3.46, 95% CI: 2.21–5.39), whereas college education or higher was protective (HR: 0.53, 95% CI: 0.32–0.88).

Conclusion

RTD occurred in 22% of AH patients within 90 days postrecovery, highlighting the need for early AUD interventions. Frequent drinking days at baseline and lower education were strongly linked to early RTD.

Maternal childhood adversity as an upstream vulnerability for prenatal alcohol use and maternal mental health

Ludmila N. Bakhireva, Xingya Ma, Sonia Macias Rodriguez, Melissa H. Roberts — Mon, 06 Apr 2026 08:00:01 -0700

This study examined associations between maternal adverse childhood experiences (mACEs) and alcohol use in pregnancy, and evaluated the independent and joint effects of mACEs and alcohol on maternal mental health. High mACEs were nearly twice as common in the Alcohol group as in Controls, with physical abuse, household substance use, and family incarceration particularly overrepresented. Both exposures were associated with increased mental health symptoms, with the greatest burden observed among women experiencing both mACEs and alcohol use.

Abstract

Background

Maternal mental health and substance use during pregnancy often co-occur, yet antecedent factors contributing to both remain understudied. This analysis examined associations between maternal adverse childhood experiences (mACEs) and (a) alcohol use and (b) stress, mood, and trauma symptoms during pregnancy.

Methods

The ENRICH-2 cohort recruited pregnant individuals into mild-to-moderate Alcohol and Control groups. Alcohol use was assessed via prospective interviews and ethanol biomarkers. Maternal childhood adversity was measured with a 10-item Adverse Childhood Experiences (ACE) questionnaire, and maternal mental health was evaluated using the Perceived Stress Scale (PSS), Edinburgh Depression Scale (EDS), Generalized Anxiety Disorder-7 (GAD-7), and PTSD Checklist for DSM-5 (PCL-5). Prevalence of High mACEs (≥4) and specific ACE categories were compared using chi-squared tests. Spearman correlation examined the association between absolute alcohol per day (AAD) and mACEs in the Alcohol group. Mean mental health scores across Control, High mACEs, Alcohol, and Alcohol+High mACEs groups were compared by ANOVA and multivariable linear regression.

Results

Among 164 participants (58 Alcohol, 106 Control), the prevalence of High mACEs was almost double in the Alcohol compared to the Control group (37.9% vs. 20.8%, p = 0.02). For the Alcohol group, there was a positive correlation between AAD and mACEs (ρ = 0.18, p = 0.02). The mACEs categories of physical abuse, household exposure to substance use, and incarceration of a family member were significantly higher in the Alcohol group (all p < 0.05). Adjusted regression models demonstrated that both High mACEs and Alcohol groups were associated with increases in maternal mental health symptom scores, with the Alcohol+High mACEs group showing the largest model-estimated increases across all outcomes (all p values < 0.01).

Conclusions

Results highlight mACEs as an upstream vulnerability associated with prenatal alcohol use and poorer maternal mental health, suggesting that mACEs—or their sequelae—may function as a contextual risk factor in pregnancy.

The relationship between alcohol use disorder, measures of cognitive decline, and Alzheimer disease biomarkers in middle aged and older adults

Mon, 06 Apr 2026 08:00:00 -0700

In this study, we examined associations between alcohol use disorder (AUD), cognitive decline, and Alzheimer's disease (AD) biomarkers in middle aged and older adults. Moderate to severe AUD was associated with increased cognitive decline, highlighting AUD as a potentially modifiable risk factor for cognitive decline in the aging population.

Abstract

Background

Alcohol use disorder (AUD) is associated with increased risks of some neuropsychiatric conditions and early-onset dementia. However, the association between Alzheimer disease (AD) and AUD is poorly characterized. To address this, we studied associations between AUD, cognition, and measures of AD neuropathology.

Methods

We measured a lifetime history of AUD, cognitive decline, and blood biomarkers for AD in middle-aged and older participants (47–87 years) from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA) (N = 392). Cognitive decline was measured using the Eight-item Informant Interview to Differentiate Aging and Dementia (AD8) (N = 366); 154 individuals had AD biomarkers derived from plasma measurements (Amyloid Probability Score 2, Aβ42/Aβ40, and %p-tau217). We used Poisson regression models to evaluate the relationship between AUD, age, and cognitive decline. AUD was categorized as no AUD, mild AUD, or moderate-to-severe AUD, and age was modeled as a piecewise linear variable segmented by decade. Linear regressions were used to assess the association between AD blood biomarkers and AUD.

Results

Analyses revealed a significant association between moderate-to-severe AUD and increased cognitive decline in middle-aged and older adults (RR = 1.4, p < 0.001). While a greater proportion of participants with moderate-to-severe AUD met the Aβ42/Aβ40 threshold for predicting elevated brain amyloid compared to those with mild or no AUD, consistent with our hypothesis, this trend did not achieve statistical significance.

Conclusions

These results underscore the importance of addressing AUD as a potentially modifiable risk factor for cognitive decline in middle aged and older adults. Further study is needed to understand the link between AUD and AD biomarkers.

Dpp6 knockout mice exhibit increased ethanol conditioned place preference and acute ethanol‐induced anxiolytic behavior

Maribel Hernández, Amanda M. Barkley‐Levenson — Sat, 04 Apr 2026 21:28:59 -0700

Dpp6 knockout mice were evaluated for ethanol conditioned place preference and ethanol effects on open field behavior. Homozygous knockout males developed significant place preference, and male and female knockouts exhibited ethanol-induced anxiolysis and sedation after 2 g/kg ethanol relative to wild-type littermates. Thus, Dpp6 is important for ethanol-related behaviors.

Abstract

Background

The gene DPP6 has been associated with behavioral phenotypes of alcohol use disorder (AUD) in recent human genome-wide association studies. DPP6 encodes an auxiliary subunit that modulates A-type voltage-gated potassium channels, particularly Kv4.2.

Methods

To further assess the role of this gene in ethanol-related traits, we tested Dpp6 knockout (KO) and wild-type mice for ethanol (EtOH) conditioned place preference (CPP), locomotor activity, and ethanol-induced anxiolysis.

Results

Male homozygous KO mice (HOM) showed greater preference for the ethanol-paired (2 g/kg) context compared to wild-type littermates (WT) and heterozygous KO mice (HET), while female mice showed no genotypic difference. HOM of both sexes exhibited greater novelty-induced hyperactivity in the CPP apparatus than HET and WT mice in the first 2 min. In a separate experiment, HOM mice showed enhanced locomotor activity following a 1.5 g/kg EtOH injection; however, they also displayed greater locomotor activity during habituation, suggesting basal locomotor differences. Following 1.5 and 2 g/kg injections, HOM mice exhibited EtOH-induced anxiolysis in the first 5 min, while the HET and WT mice did not. Lastly, HOM mice displayed a significant sedative response compared to WT animals following a 2 g/kg injection of ethanol.

Conclusions

Ultimately, these findings validate a role for Dpp6 in modulating ethanol's rewarding, anxiolytic, and sedative effects in a sex-dependent manner.

Correction to “Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta‐analysis of data from six prospective longitudinal U.S. cohorts”

Wed, 01 Apr 2026 20:51:19 -0700

Alcohol, Clinical and Experimental Research, Volume 50, Issue 4, April 2026.

Issue Information

Mon, 30 Mar 2026 23:15:10 -0700

Alcohol, Clinical and Experimental Research, Volume 50, Issue 4, April 2026.

The 10‐year stability of three subscale scores of the Self‐Report of the Effects of Alcohol measure and their relationship to changes in drinking quantities over the same period

Mon, 30 Mar 2026 23:13:27 -0700

The Self-Report of the Effects of Alcohol (SRE) questionnaire records the number of drinks needed for effects across three life periods; a higher number of drinks required for effects indicates higher risks for future alcohol problems. This paper reports changes in SRE subscale scores measured five times over 10 years in 331 drinkers. The SRE subscale related to very early drinking experiences, SRE-5, does not change over time, but subscales related to more recent experiences do change in relation to recent drinking histories.

Abstract

Objectives

The retrospective self-report of the effects of alcohol (SRE) questionnaire generates three scores reflecting drinking quantities required for effects: SRE-5 (first five times of drinking), SRE-3 (recent 3 months of drinking), and SRE-H (heaviest drinking). Data to date indicate that SRE-5 scores, potentially reflecting genetic effects, have high reliabilities across 9 months. Data presented here evaluated the consistencies of all three SRE scores obtained five times over a decade.

Method

Participants were 331 young adults (45% male) from the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective Study of youth who completed the SRE and were evaluated at least five times using the Semi-Structured Assessment for the Genetics of Alcoholism interview. Analyses documented changes in SRE scores, changes in drinking quantities, and the relationship between these measures over time using repeated measures ANOVA and regression analyses.

Results

SRE-5 scores did not change significantly across evaluations despite significant changes in drinking quantities. SRE-3 and SRE-H demonstrated significant changes over time that related to changes in drinking quantities during each period. Participants with low levels of response (low LRs) to alcohol, based on a median split of SRE-5 at Time 1, were likely to remain low LR throughout the decade.

Conclusions

This is the first report on the longer-term consistency of all three SRE scores during a decade of life in which a person's heaviest drinking and AUD development are likely to occur. Results indicate that retrospective SRE-5 scores, potentially reflecting genetic predispositions to AUD, do not change over a decade despite changes in drinking patterns.