Severe Alcohol Use Disorder Research Articles

Probenecid as a pharmacotherapy for alcohol use disorder: Arandomized placebo-controlled alcohol interaction trial.

This study shows the first evidence for pannexin 1 channels as a new target to develop medications for alcohol use disorder (AUD). Due to its history of long-term safe clinical use and preclinical evidence of reducing excessive alcohol intake in rodents, probenecid has clinical potential for AUD. We conducted a Phase I/IIa randomized, double-blind, placebo-controlled, crossover trial investigating the safety, tolerability, and efficacy of an oral dose of probenecid (2 g) when administered with alcohol (0.08 g/dL) in individuals who regularly consume alcohol to the 0.08 g/dL level (N = 35) and in individuals with mild to severe AUD. Alcohol pharmacokinetics and subjective responses were evaluated to assess potential interactions between probenecid and alcohol. Alcohol craving, inflammatory biomarkers, cognitive assessments, and hemodynamics were assessed as additional alcohol research domains. All outcomes were assessed both in the ascending and descending limb of alcohol intoxication using Generalized Estimating Equation. Probenecid did not exert any significant effect on alcohol pharmacokinetics and did not affect alcohol stimulation or sedation. Probenecid, compared to placebo, significantly decreased alcohol craving during the alcohol ascending limb. Inflammatory biomarkers, cognitive performance following alcohol ingestion, and hemodynamics were likewise not affected by probenecid administration. Analysis of sex as a biological variable revealed no differences of probenecid compared to placebo. Taken together, our data support the potential of probenecid for treatment of AUD and suggest that pannexin 1 channels represent a novel emerging therapeutic target for the development of new pharmacotherapies for treating AUD.

Correlates of post-hospitalization naltrexone adherence for alcohol use disorder

IntroductionHospitalizations present an opportunity to initiate naltrexone for patients with alcohol use disorder (AUD). Understanding factors associated with post-hospitalization adherence could inform practice. MethodsThis study is a secondary analysis of a clinical trial in which patients with AUD were randomized to oral (PO) versus long-acting injectable (LAI) naltrexone at hospital discharge. The outcome of this secondary analysis was naltrexone adherence 3 months after discharge, defined as receipt of at least 2 out of 3 monthly injections or the equivalent days of self-reported PO medication use (60 out of 90). We used baseline socio-demographics, substance use history, health status, healthcare utilization, and randomization arm to construct multivariable logistic regression models to identify correlates of adherence. ResultsWe evaluated patients who initiated naltrexone treatment, 124 randomized to PO and 120 to LAI (overall mean age 49 years, 80 % male, 51 % Black, 47 % unhoused, and 91 % with severe AUD). At 3 months, 50 % of patients were adherent. LAI naltrexone (aOR 3.88; 95 % CI 2.17–7.13), recent office visit (aOR 2.01; 95 % CI 1.10–3.72), and age (aOR per 10-year increase 1.37; 95 % CI 1.02–1.88) were associated with increased odds of adherence. Unhoused status (aOR 0.54; 95 % CI 0.30–0.98) and cocaine use (aOR 0.35; 95 % CI 0.17–0.71) were associated with decreased odds of adherence. ConclusionsLAI naltrexone for AUD at hospital discharge was associated with better adherence at 3 months vs PO. Access to LAI naltrexone and targeted interventions for patients with cocaine use or who are unhoused hold potential to improve naltrexone adherence.

Elevations in interleukin-8 levels in individuals with alcohol use disorder and clinical insomnia symptoms.

Insomnia commonly co-occurs with alcohol use disorder (AUD) and predicts poorer outcomes for those with AUD. Insomnia and AUD are individually associated with increases in systemic inflammation. Insomnia and inflammation both serve as risk factors for relapse in AUD. However, little is known about the relationship between insomnia and systemic inflammation in individuals with AUD. Therefore, the present study examined the relationship between the severity of insomnia symptoms and plasma levels of inflammatory cytokines in a sample of treatment-seeking individuals with an AUD. This secondary analysis included 101 (61M/40F) individuals with an AUD. Participants were categorized into groups based on their scores on the Insomnia Severity Index: no insomnia (n = 47), subthreshold insomnia (n = 37), and clinical insomnia (n = 17). Participants provided blood samples to measure plasma levels of four peripheral markers of inflammation (IL-6, IL-8, TNF-α, and CRP). Inflammatory marker levels were compared between groups. Interactive effects of sex and AUD severity were examined. There was a significant main effect of insomnia group on log IL-8 levels (F = 6.52, p = 0.002), such that individuals with AUD and clinical insomnia had higher log IL-8 levels compared to both the no insomnia and subthreshold insomnia groups (ps ≤ 0.05). Sex and AUD severity interacted with this relationship, such that men with clinical insomnia and AUD and individuals with severe AUD had higher log IL-8 levels. There were no significant effects of insomnia on IL-6, TNF-α, or CRP levels. The present study identified a specific elevation in IL-8 levels in individuals with an AUD and clinical insomnia that was not identified in other markers of peripheral inflammation (IL-6, TNF-α, CRP). Sex and AUD severity interacted with insomnia symptoms, indicating that those with clinical insomnia and severe AUD or male sex may be the most vulnerable to the inflammatory consequences associated with AUD and clinical insomnia symptoms.

Corticotropin-Releasing Factor Modulates Binge-Like Ethanol Drinking in a Sex-Dependent Manner: Impact of Amygdala Deletion and Inhibition of a Central Amygdala to Lateral Hypothalamus Circuit

BackgroundBinge alcohol drinking is a dangerous behavior that can contribute to the development of more severe alcohol use disorder. Importantly, the rate and severity of alcohol use disorder has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin-releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in CRF systems. MethodsIn the current report, we characterized CRF+ neurocircuitry arising from the central nucleus of the amygdala (CeA) and innervating the lateral hypothalamus (LH) in the modulation of binge-like ethanol intake in male and female mice. ResultsUsing chemogenetic tools, we found that silencing the CRF+ CeA to LH circuit significantly blunted binge-like ethanol intake in male but not female mice. Consistently, genetic deletion of CRF from neurons of the CeA blunted ethanol intake exclusively in male mice. Furthermore, pharmacological blockade of the CRF type-1 receptor in the LH significantly reduced binge-like ethanol intake in male mice only, while CRF type-2 receptor activation in the LH failed to alter ethanol intake in either sex. Finally, a history of binge-like ethanol drinking reduced CRF messenger RNA levels in the CeA regardless of sex. ConclusionsThese observations provide novel evidence that CRF+ CeA to LH neurocircuitry is more sensitive for modulating binge-like ethanol intake in male mice, which may provide insight into the mechanisms that guide known sex differences in binge-like ethanol intake.

Pain and unhealthy alcohol use among people living with HIV: A prospective cohort study.

Unhealthy alcohol use is prevalent among people living with HIV/AIDS (PLWH) and contributes to impaired functioning, diminished quality of life, and poorer HIV outcomes. Common cooccurring conditions such as chronic pain may be associated with negative outcomes both directly and through its influence on unhealthy drinking itself. However, there is relatively little known about how pain influences unhealthy drinking among PLWH over time. The current study examined whether pain was associated with indices of unhealthy alcohol use, namely heavy drinking and alcohol use disorder (AUD) assessed 12 months later. The study sample (n = 207) was from the Boston Alcohol Research Collaboration on HIV/AIDS (ARCH) Cohort, a prospective cohort of PLWH with a history of illicit substance or unhealthy alcohol use. We conducted logistic regression analyses to examine the associations between pain and both heavy drinking and AUD status (DSM-5 criteria) (yes/no) over time. In secondary analyses, we examined whether pain was associated with greater AUD severity and whether pain interference was associated with heavy drinking and AUD outcomes. We found that pain at baseline was associated with greater odds of AUD [aOR = 2.29 (95% CI: 1.13, 4.64), p = 0.02] but not heavy drinking [aOR = 0.91 (95% CI: 0.44, 1.88), p = 0.79] at 12 months. Pain was also associated with more severe AUD. Analyses of pain interference showed similar results. Pain is prospectively associated with higher odds of AUD among PLWH with a substance/unhealthy alcohol use history. Providers should routinely address pain among PLWH to improve AUD outcomes.

Genetic Risk for Alcohol Use Disorder in Relation to Individual Symptom Criteria: Do Polygenic Indices Provide Unique Information for Understanding Severity and Heterogeneity?

Alcohol Use Disorder (AUD) is a heterogenous category with many unique configurations of symptoms. Previous investigations of AUD heterogeneity using molecular genetics methods studied the association between genetic liability and individual AUD symptoms at the latent level or focusing on a small number of genetic variants. Notably, these studies did not investigate potential severity differences between symptoms in their genetic analyses. Therefore, the current study aimed to examine the genetic risk for individual AUD symptom criteria by using a polygenic risk score (PRS) approach to assess the relative severity of each AUD symptom and test for associates with AUD symptoms above and beyond a unidimensional AUD construct. An AUD PRS was created using summary statistics obtained from published genome-wide association studies (GWAS), and Multiple Indicators Multiple Causes (MIMIC) models were employed to examine the effect of the PRS on overall AUD severity as well as on individual symptoms after accounting for this overall effect. The phenotypic severity of AUD symptoms was highly correlated with the genetic severity of AUD symptoms (r = 0.78). Results of MIMIC models indicated that the AUD PRS significantly predicted the AUD factor. Regression paths testing the unique, direct effects of the PRS on individual AUD symptoms, independent of the latent AUD factor, were not significant. These results imply that PRSs derived from GWAS of AUD influence symptom expression through a single genetic factor that is highly correlated with the relative severity of individual symptoms when measured at the phenotypic level. Item-level GWAS of AUD symptoms are needed to further parse heterogeneous symptom expression and allow for more nuanced tests of these conclusions.

Early detection of liver disease in patients with alcohol use disorder improves long-term abstinence.

Excessive alcohol consumption is a major global health concern, contributing to millions of deaths annually and a significant proportion of cirrhosis cases; however, standardized protocols for early identification of alcohol-associated liver disease are lacking. In this retrospective cohort study, we aimed to understand the prevalence and risk factors associated with elevated liver stiffness measurement (LSM) in high-risk patients with alcohol use disorder (AUD) and identify variables associated with longitudinal abstinence and outcomes. Veterans with severe AUD without known liver disease admitted to a 35-day residential substance use treatment program were offered liver health screening, including Fibroscan evaluation. Assessment of AUD severity and liver health outcomes were evaluated longitudinally by chart review. In a cohort of 257 veterans with severe AUD admitted to residential treatment, 185 underwent Fibroscan evaluation, and 22 were identified to have elevated LSM concerning for compensated advanced chronic liver disease. Patients with elevated LSM were more likely to remain abstinent after 1 year. About 41% of patients with LSM ≥ 10kPa (5% of all screened patients) were confirmed to have cirrhosis on follow-up and incorporated into routine hepatology care. Screening of liver disease in high-risk populations with non-invasive imaging modalities provides an opportunity to identify patients at risk for compensated advanced chronic liver disease before decompensation. Identification of increased risk for advanced chronic liver disease may promote abstinence in patients with severe AUD. Collaboration between mental health professionals and hepatologists is critical for the integration of care for patients with AUD and liver disease.

Is severe alcohol use disorder really associated with increased utilitarian moral judgment? Exploration using the CNI model

ObjectivesThe psychology of moral decision-making classically contrasts utilitarianism (based on consequences) and deontology (based on moral norms). Previous studies capitalizing on this dichotomy have suggested the presence of a utilitarian bias among patients with severe alcohol use disorder (SAUD). We aimed to further disentangle the processes involved in such bias through a more validated approach, the CNI model of moral decision-making. This model allows to go further than the classical approach by distinguishing sensitivity to consequences (C), to moral norms (N), and general preference for inaction over action (I) in response to moral dilemmas. MethodsThirty-four recently detoxified patients with SAUD and 34 matched control participants completed a battery of 48 dilemmas derived from the CNI model, as well as social cognition tasks. ResultsIn contrast with the utilitarian bias suggested in previous studies based on the classical approach, patients with SAUD did not show an increased sensitivity to consequences in comparison with control participants. However, they showed a reduced sensitivity to moral norms, as well as a greater action tendency. These biases were not related to social cognition deficits. ConclusionsPatients with SAUD are not more utilitarian than healthy controls, this previously reported bias being artificially generated by the methodological limits of the classical approach. Instead, they present a reduced sensitivity to moral norms and an action bias, which might impact their interpersonal relations and contribute to the social isolation frequently reported in this population, thus identifying moral decision-making as a new therapeutic lever in SAUD.

Implications of the shift to DSM-5 for alcohol use disorder prevalence estimates in the National Survey on Drug Use and Health.

The Substance Abuse and Mental Health Services Administration's annual National Survey on Drug Use and Health (NSDUH) is a commonly used source for estimating trends in alcohol use disorders (AUD) in the United States. From 2015 to 2019 the annual prevalence of people diagnosed with either Diagnostic and Statistical Manual 4th edition (DSM-IV) alcohol abuse or dependence ranged from 5.3 to 5.9%. More recent estimates, using the DSM 5th edition (DSM-5) AUD diagnostic formulation, have been higher, with AUD base rates ranging from 10.1 to 10.7% from 2020 to 2022. This study aimed to compare the past 12-month base rates of AUD in the United States general population when using the DSM-5 versus DSM-IV AUD (i.e. abuse or dependence) and assess the AUD severity of individuals captured with each diagnostic formulation using DSM-5 AUD symptom counts. We examined descriptive trends in the rate of past-year NSDUH AUD diagnoses from 2015 to 2022. We contrasted them with trends in drinking behavior: the percentage of individuals who had ever reported drinking and the number of drinking days and binge drinking days for those who drink. We also analyzed the concordance between DSM-IV and DSM-5 AUD diagnoses in the 2020 NSDUH, which concurrently assessed AUD with both diagnostic formulations. The transition to DSM-5 AUD formulation coincided with a drastic increase in AUD prevalence rates that occurred without increases in drinking behavior. In 2020 NSDUH data, the estimated past-year DSM-5 AUD prevalence rate was 10.1% compared with a 5.4% rate of past-year DSM-IV abuse or dependence. The DSM-5 AUD formulation captured more mild-severity individuals than the DSM-IV formulation. Higher recent base rates of alcohol use disorders (AUD) in the National Survey on Drug Use and Health are likely, at least partially, explained by measurement changes in AUD; specifically, the shift from DSM-IV abuse or dependence to DSM-5 AUD. The DSM-5 formulation appears substantially more inclusive than the DSM-IV formulation, leading to a larger number of mild severity individuals being captured.

Social decision making in binge drinking: An exploration through moral dilemmas.

The continuum hypothesis proposes that binge drinking and severe alcohol use disorder (SAUD) share qualitatively similar cognitive and emotional impairments. In SAUD, these deficits have a demonstrated impact on social decision making, resulting in a utilitarian bias. Namely, when confronted with moral dilemmas, patients with SAUD tend to focus on the consequences of their actions rather than on social norms. However, social decision-making abilities remain unexplored in binge drinking. We offered the first insights on the generalization of the continuum hypothesis to social decision making, through a multinomial processing tree model applied to moral dilemmas, the "CNI model" of moral decision making. We compared 35 binge drinkers (20 females) and 36 light drinkers (21 females) on a battery of 48 moral dilemmas involving interpersonal relations from the CNI model, through multinomial modeling analyses. In each dilemma, participants were asked if they would perform the described action, generating individual scores for sensitivity to consequences, sensitivity to norms, and inaction tendency. The statistical model related to the CNI approach fits the data well. Binge drinkers and controls did not differ regarding their sensitivity to consequences nor their sensitivity to moral norms, and both groups displayed an equal inaction tendency in response to moral dilemmas. We provided insights to better understand the specific (socio)cognitive domains impaired in subclinical populations with alcohol use disorder. We showed preserved social decision making in binge drinking, which suggests that the continuum hypothesis documented for classical neurocognitive functions does not extend to complex social abilities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Examination of the mild, moderate, and severe alcohol use disorder severity indicators using a nationally representative sample.

The Diagnostic and Statistical Manual of Mental Disorders, fifth edition conceptualizes alcohol use disorder (AUD) as a single continuum with indicators to denote the level of severity along this spectrum with the presence of 2-3, 4-5, or 6 + symptoms indicating mild, moderate, and severe AUD, respectively. However, despite the labels of these indicators, it remains unclear how individuals compare across these indicators, both in terms of AUD severity, but also risk for other related problems (e.g., depression). Confirmatory factor analysis was conducted on past year AUD symptoms to obtain estimates of latent AUD severity using data from the 2020 National Survey on Drug Use and Health (unweighted n = 31,941). The range and distribution of latent trait estimates were then compared across AUD diagnostic statuses (i.e., no AUD, mild, moderate, and severe). Multinomial regressions were then used to compare diagnostic groups based on alcohol use, problems with other substances, treatment utilization, and mental/physical health. Results indicated very limited overlap in latent severity estimates between individuals with different severity indicators. Multinomial regression results demonstrated that some measures increased in a roughly stepwise fashion across AUD indicators (e.g., alcohol use and drinking behavior), while many did not. Results partially support the current AUD indicators as AUD severity and co-occurring problems did broadly increase across the indicators. However, the present study also explores several ways to improve these indicators in future AUD formulations. For example, having indicators that account not only for the quantitative but also the qualitative differences in AUD presentation at different severity levels. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The association between adverse childhood experiences and alterations in brain volume and cortical thickness in adults with alcohol use disorder.

Previous studies have established a connection between adverse childhood experiences (ACE) and alcohol use disorder (AUD), both of which are associated with alterations in grey matter volume (GMV) and cortical thickness (CT). The current study aimed to assess the neurobiological impact of ACE specifically in the context of AUD, as well as the role of maltreatment type (i.e., abuse or neglect) and timing. Structural MRI data were collected from 35 adults with AUD (mean age: 40; 31% female) and 28 healthy controls (mean age: 36; 61% female). ACE were assessed retrospectively using the Childhood Trauma Questionnaire, and the Maltreatment and Abuse Chronology interview. Global and regional GMV and CT were estimated using voxel- and surface-based morphometry. Relative to the healthy controls, the AUD group had significantly reduced CT in the left inferior frontal gyrus, left circular sulcus of the insula and subcentral gyrus and sulci (cluster C1), and in the central sulcus and precentral gyrus (cluster C2). Within the AUD group, a reduction of CT in cluster C1 was significantly associated with higher severity of ACE and AUD. Type and timing analyses revealed a significant association between higher levels of abuse at ages 13 to 15 and reduced CT in cluster C1 within the AUD group. In adults with AUD, abuse experienced during early adolescence is associated with reduced CT in regions involved in inhibitory control, indicating the potential relevance of cognitive pathways in the association between ACE and AUD. Longitudinal studies are needed to confirm and expand upon current findings.

Treatment Needs of Patients With Severe Alcohol Use Disorders

Background: People with alcohol use disorders (AUDs) have varied needs while they seek treatment. Understanding and focusing on the needs will improve treatment outcomes. The objective of the study is to qualitatively assess the treatment-related needs of patients with AUDs admitted to a tertiary care treatment center. Methods: A semi-structured questionnaire with anchor questions was developed based on a literature review and key informant interviews. All the interviews were audio recorded, transcribed, and color-coded manually. Two reviewers reviewed the codes. Themes and subthemes were generated using thematic inductive analysis. Results: Among 15 patients interviewed, all the patients had severe AUD (100%), were married (100%), were primarily males (86.6%), and more than half below the poverty line (53.4%), with a mean age of 41.1 years (SD = 9.5). Four major themes of treatment needs were identified: (a) individual, (b) family-related, (c) hospital-related, and (d) community-related. Among individual needs-medication-related, psychological, and occupational were prominent. Addressing family conflict and supporting the family are the significant subthemes for family-related needs. The behavior of the treating team, environmental needs, and diverse services were significant hospital-related needs. Awareness, accessibility, availability, and affordability of treatment services were the major community-related needs. Conclusion: The study highlights diverse needs extending from individual to community among people with AUDs. A holistic treatment model to address these needs will improve the quality of care and treatment outcomes.

Medications for Alcohol Use Disorder: Rates and Predictors of Prescription Order and Fill in Outpatient Settings.

Alcohol use disorders (AUD) are prevalent and responsible for substantial morbidity and mortality; yet efficacious treatments are underused. Previous studies have identified demographic and clinical predictors of medication fills, yet these studies typically do not include patients who were prescribed a medication but did not fill it. To examine rates of and factors associated with prescription order and prescription fill for medications for AUD (MAUD) among individuals diagnosed with AUD in outpatient settings. In a cross-sectional analysis, we used multivariate logistic regression to identify factors associated with prescription order and fill. We used data from the Optum Labs Data Warehouse that linked 2016-2021 de-identified claims and electronic health record (EHR) data, allowing us to observe prescription orders and whether they were filled. We identified 14,674 patients aged ≥ 18 who had an index outpatient encounter with an AUD diagnosis in the EHR. We computed the proportion for whom a MAUD prescription was ordered within 1year of index visit, and for whom one was filled within 30days of the order. 5.8% of the sample had a MAUD prescription order within 1year of their index visit. Among those with an order, 87% filled their MAUD prescription within 30days of receipt (i.e., 5.1% of full sample). After multivariable adjustment, receipt of a MAUD prescription order was more likely for patients who were female (adjusted odds ratio (aOR) [95%CI] = 1.44 [1.24-1.67]), orhad moderate or severe AUD (1.74 [1.50-2.01]). Patients receiving an order were more likely to fill it if they had a comorbid mental disorder (1.64 [1.09-2.49]). The low rate of prescription orders was notable. Low use of MAUD appears to result chiefly from prescription order decisions, rather than from prescription fill decisions made by patients.

Reduction of Psychosis Proneness in a Daycare Hospital Program for Patients with Severe Alcohol Use Disorder

Objectives Anxiety and depressive symptoms, as well as cognitive dysfunctions, improve with abstinence in individuals with alcohol use disorders (AUD), but less is known about psychotic features. The objective of this study was to evaluate the psychosis proneness in a sample of individuals with severe AUD and potential changes after alcohol withdrawal. Method An observational study was conducted, assessing prospectively Peter’s Delusional Inventory scale (PDI); anxiety and depression symptoms by MADRS and cognitive functioning by the MoCA at entry in daycare hospital (D0) and after 30 days (D30). Individuals with schizophrenia, chronic delusional disorder and bipolar disorder were excluded. Wilcoxon tests were used to evaluate the evolution between D0 and D30, and linear regressions were conducted to test the association between delta PDI and the variables that could be potential confounders. Results Forty individuals (72% males) with a mean age of 50 ± 9 years old and AUD evolved for 15 ± 11 years were included. After one month, PDI score decreased significantly (p = .001), and several biological and clinical parameters improved significantly with abstinence or consumption reduction: GGT (p = .003), MoCA (p < .001), MADRS (p = .047). Conclusion We observed a decrease in delusional thinking along abstinence and/or consumption reduction. To our knowledge, this is the first research to study psychosis proneness evolution in patients with severe AUD. Replications are required in independent samples with larger sample size.

Triple network resting-state functional connectivity patterns of alcohol heavy drinking.

Previous neuroimaging research in alcohol use disorder (AUD) has found altered functional connectivity in the brain's salience, default mode, and central executive (CEN) networks (i.e. the triple network model), though their specific associations with AUD severity and heavy drinking remains unclear. This study utilized resting-state fMRI to examine functional connectivity in these networks and measures of alcohol misuse. Seventy-six adult heavy drinkers completed a 7-min resting-state functional MRI scan during visual fixation. Linear regression models tested if connectivity in the three target networks was associated with past 12-month AUD symptoms and number of heavy drinking days in the past 30days. Exploratory analyses examined correlations between connectivity clusters and impulsivity and psychopathology measures. Functional connectivity within the CEN network (right and left lateral prefrontal cortex [LPFC] seeds co-activating with 13 and 15 clusters, respectively) was significantly associated with AUD symptoms (right LPFC: β = .337, p-FDR = .016; left LPFC: β = .291, p-FDR = .028) but not heavy drinking (p-FDR > .749). Post-hoc tests revealed six clusters co-activating with the CEN network were associated with AUD symptoms-right middle frontal gyrus, right inferior parietal gyrus, left middle temporal gyrus, and left and right cerebellum. Neither the default mode nor the salience network was significantly associated with alcohol variables. Connectivity in the left LPFC was correlated with monetary delay discounting (r =.25, p = .03). These findings support previous associations between connectivity within the CEN network and AUD severity, providing additional specificity to the relevance of the triple network model to AUD.

The Role of Perceived Stress in the Relation between Childhood Maltreatment and Severity of Alcohol Use Disorder: A Mediation Analysis

Introduction: Experiences of Childhood Maltreatment (CM) relate to relapse and lower treatment success in Alcohol Use Disorder (AUD), one of the most prevalent substance use disorders. However, the exact mechanisms of this relationship still remain unclear. This study examines perceived stress and “drinking to cope with negative affect” (coping) as possible mediators in this relationship. Moreover, it aims at uncovering the differential effects of the subtypes of CM. Methods: N = 96 individuals (42% women; mean age 41 ± 13 years) including healthy controls and individuals with varying severity of AUD and CM completed the Alcohol-Dependence Scale, Childhood Trauma Questionnaire, Perceived Stress Scale and German Inventory of Drinking Situations. Mediation analyses including perceived stress as a mediator between CM (and subtypes) and severity of AUD, as well as a serial mediation of the relationship between CM and AUD severity by perceived stress and coping were conducted. Results: Perceived stress significantly mediated the relation between CM and AUD severity and the serial mediation by perceived stress and coping turned out significant. Subtype-specific analyses did not yield significant results. Conclusion: This study reinforces perceived stress as a potential mechanism in the relation between CM and AUD severity. Moreover, coping further mediated the relationship between CM and AUD severity. Our results suggest including screening for CM (subtypes) in clinical routine in order to individually emphasize interventions focusing on stress regulation, as well as on developing healthy coping mechanisms, in patients with AUD. This might prevent heightened stress sensitivity, relapse and further maintenance of AUD.

Altered Physiological, Affective, and Functional Connectivity Responses to Acute Stress in Patients With Alcohol Use Disorder

BackgroundThere is evidence that the processing of acute stress is altered in alcohol use disorder (AUD), but little is known about how this is manifested simultaneously across different stress parameters and which neural processes are involved. The current study examined physiological and affective responses to stress and functional connectivity in AUD. MethodsSalivary cortisol samples, pulse rate, and affect ratings were collected on 2 days from 34 individuals with moderate or severe AUD during early abstinence and 34 control participants. On one of the days, stress was induced, and on the other day, a nonstressful control task was performed. Following the intervention, participants underwent functional magnetic resonance imaging to assess functional connectivity, with a focus on cortical and subcortical seed regions previously reported to be involved in AUD and/or stress. ResultsFor pulse rate and cortisol, stress responses were blunted in AUD, whereas the affective response was stronger. Neuroimaging analyses revealed stress-related group differences in functional connectivity, involving the connectivity of striatal seeds with the posterior default mode network, cerebellum, and midcingulate cortex and of the posterior default mode network seed with the striatum and thalamus. ConclusionsThe results suggest a dissociation between subjectively experienced distress and the physiological stress response in AUD as well as stress-related alterations in functional connectivity. These findings highlight the complex interplay between chronic alcohol use and acute stress regulation, offering valuable considerations for the development of therapeutic strategies.

Social episodic memory in severe alcohol use disorder: Positive encoding bias and negative bias in accessibility of interpersonal information.

Alterations in higher-order social cognition are well documented in individuals with severe alcohol use disorder (SAUD). However, the basic mechanisms underpinning them are not well understood. This knowledge gap hampers the development of targeted therapeutic interventions. Here, we investigated whether individuals with SAUD show abnormalities in social episodic memory processes, which may represent relevant candidate mechanisms for alterations in social cognition. Recently detoxified patients with SAUD and matched healthy controls (HCs) completed two experimental tasks. We first used a Social Recognition Task in 40 SAUD patients and 40 HCs to measure the participants' ability to implicitly memorize the facial identity and emotion of novel interpersonal cues (i.e., dynamic facial expressions of anger and happiness). We then used a Social Memory Accessibility Task in 29 SAUD patients and 30 HCs) to measure participants' access to and fluency for already existing social memories by asking them to retrieve as many specific positive and negative interpersonal events as possible within equal time limits. In the Social Recognition Task, we found that, compared to HCs, patients with SAUD had a globally lower recognition performance for the facial identities of novel social stimuli, but a preserved bias toward positive information. Conversely, in the social memory accessibility task, patients showed greater access to and fluency for negative interpersonal memories than controls (no group differences were observed for positive ones), resulting in a negative accessibility bias. This exploration of episodic social memory in individuals with SAUD showed (1) a preserved bias for the encoding of positive versus negative novel social information, and (2) greater access to negative than positive interpersonal memories. These results enhance our understanding of socio-affective processing in individuals with SAUD and identify social memory alterations that may contribute to social cognition and interpersonal difficulties.

Effectiveness of psychosocial interventions for alcohol use disorder: a systematic review and meta-analysis update

ABSTRACT Background: Given the accumulating research, evolving psychosocial treatment, and equivocal findings, updating WHO’s Mental Health Gap Action Programme-2015 was necessary to ensure guidelines reflect effective strategies for alcohol use disorder (AUD). Objective: To estimate the effects of psychosocial interventions on drinking and related outcomes. Methods: We included randomized controlled trials published between January 2015 and June 2022 on adults with alcohol dependence (ICD 10/DSM-IV) and moderate to severe AUD (DSM-5), and those examined psychosocial interventions against treatment-as-usual (TAU) and active controls. Eight databases and registries were searched. Relative Risk (RR) and standardized mean difference (SMD) were used for dichotomous and continuous outcomes. We used Cochrane’s risk of bias assessment (RoB2). Results: Of 873 screened records, 14 and 13 studies in the narrative synthesis and meta-analysis. Of the 2,575 participants, 71.5% were men. Thirteen studies used ICD 10/DSM IV diagnosis. Compared to TAU, any psychosocial intervention increased the relative risk of abstinence by 28% [N = 7, RR = 1.28, 95% CI: 1.07 to 1.53, p = .01, NNT = 9]. There were minimal heterogeneity and no evidence of publication bias. Psychosocial interventions were not effective in reducing the drinking frequency (n = 2, Hedge’s g = −0.10, 95% CI: −0.46 to 0.26, p = .57) and drinks/drinking days (N = 5, g = −0.10, 95% CI: −0.37 to 0.16, p = .43). Treatment discontinuation did not differ between intervention and control groups [RR = 1.09, 95% CI: 0.66 to 1.80]. Conclusion: Psychosocial interventions are effective in improving abstinence but not in reducing drinking frequency or amount. Policymakers must consider this evidence to generate AUD treatment guidelines. Registration: PROSPERO 2022 CRD42022342608