Heterogeneity In Alcohol Use Disorder Research Articles

Factors underlying the neurofunctional domains of the Addictions Neuroclinical Assessment assessed by a standardized neurocognitive battery

The Addictions Neuroclinical Assessment (ANA) is a neurobiologically-informed framework designed to understand the etiology and heterogeneity of Alcohol Use Disorder (AUD). Previous studies validated the three neurofunctional domains of ANA: Incentive Salience (IS), Negative Emotionality (NE) and Executive Function (EF) using secondary data. The present cross-sectional observational study assessed these domains in an independent, prospective clinical sample. Adults across the drinking spectrum (N = 300) completed the ANA battery, a standardized collection of behavioral tasks and self-report assessments. Factor analyses were used to identify latent factors underlying each domain. Associations between identified domain factors were evaluated using structural equation models. Receiver operating characteristics analyses were used to determine factors with the strongest ability to classify individuals with problematic drinking and AUD. We found (1) two factors underlie the IS domain: alcohol motivation and alcohol insensitivity. (2) Three factors were identified for the NE domain: internalizing, externalizing, and psychological strength. (3) Five factors were found for the EF domain: inhibitory control, working memory, rumination, interoception, and impulsivity. (4) These ten factors showed varying degrees of cross-correlations, with alcohol motivation, internalizing, and impulsivity exhibiting the strongest correlations. (5) Alcohol motivation, alcohol insensitivity, and impulsivity showed the greatest ability in classifying individuals with problematic drinking and AUD. Thus, the present study identified unique factors underlying each ANA domain assessed using a standardized assessment battery. These results revealed additional dimensionality to the ANA domains, bringing together different constructs from the field into a single cohesive framework and advancing the field of addiction phenotyping. Future work will focus on identifying neurobiological correlates and identifying AUD subtypes based on these factors.

Examining the validity of the addictions neuroclinical assessment domains in a crowdsourced sample of adults with current alcohol use.

Several dimensional frameworks for characterizing heterogeneity in alcohol use disorder (AUD) have been proposed, including the Addictions Neuroclinical Assessment (ANA). The ANA is a framework for assessing individual variability within AUD across three domains corresponding to the proposed stages of the addiction cycle: reward (binge-intoxication stage), negative emotionality (withdrawal-negative affect stage), and cognitive control (preoccupation-anticipation stage). Recent work has evaluated the ANA's three-factor structure and construct validity, primarily in treatment-seekers with AUD. We extended this research by examining the factor structure, bias across alcohol use severity, longitudinal invariance, and concurrent and predictive validity of a novel assessment of the ANA domains in adults with past 12-month regular (10 + alcohol units/week) alcohol use. Participants recruited from Prolific (N = 732), a crowdsourced data collection platform, completed various self-report measures. A test-retest subsample (n = 234) completed these measures 30 days later. Split-half exploratory factor analysis and confirmatory factor analysis supported the three-factor structure of the ANA. The overall factor structure was invariant across 30 days. Concurrently and prospectively, ANA domains demonstrated convergent validity concerning theoretically aligned alcohol-related, psychological, and personality measures. However, there was evidence of poor discriminant validity, and several cognitive control and reward items demonstrated bias across alcohol use severity. Future research is needed to improve the measurement of ANA domains using multimodal indicators, examine longitudinal changes in domains and their relationship with alcohol use severity, characterize phenotypic subgroups based on relative levels of domains, and compare the utility of the ANA with other proposed frameworks for measuring AUD heterogeneity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Data driven mixed effects modeling of the dual process framework of addiction among individuals with alcohol use disorder.

Alcohol use disorder (AUD) comprises a continuum of symptoms and associated problems that has led AUD to be a leading cause of morbidity and mortality across the globe. Given the heterogeneity of AUD from mild to severe, consideration is being given to providing a spectrum of interventions that offer goal choice to match this heterogeneity, including helping individuals with AUD to moderate or control their drinking at low-risk levels. Because so much remains unknown about the factors that contribute to successful moderated drinking, we use dynamical systems modeling to identify mechanisms of behavior change. Daily alcohol consumption and daily desire (i.e., craving) are modeled using a system of delayed difference equations. Employing a mixed effects implementation of this system allows us to garner information about these mechanisms at both the population and individual levels. Use of this mixed effects framework first requires a parameter set reduction via identifiability analysis. The model calibration is then performed using Bayesian parameter estimation techniques. Finally, we demonstrate how conducting a parameter sensitivity analysis can assist in identifying optimal targets of intervention at the patient-specific level. This proof-of-concept analysis provides a foundation for future modeling to describe mechanisms of behavior change and determine potential treatment strategies in patients with AUD.

The Typology of Alcohol Use Disorder: Latent Class Analyses of a Population-Based Swedish Sample.

The purpose of this study was to clarify the clinical heterogeneity of alcohol use disorder (AUD) in a national Swedish sample of affected individuals using latent class analysis. Using a Swedish population-based sample of AUD cases ascertained from medical, criminal, and pharmacy registries (n = 217,071), we applied latent class analysis to sex, externalizing and internalizing syndromes before first registration, and age at first registration. The resulting types were evaluated against 15 diverse validators and degree of resemblance in relative pairs concordant for AUD. A three-class solution was preferred by fit indices. The three classes were as follows: type 1 (male preponderant, externalizing; 32%), type 2 (minimal prior psychopathology; 46%), and type 3 (mixed-sex internalizing; 23%). Repeated split-half analyses revealed the statistical stability of these solutions. Meaningful differences emerged between the classes on many validators. Type 1 had the greatest family disruption, lowest educational levels, most AUD registrations, highest rates of criminal registration, and highest genetic risk for externalizing disorders and AUD. Type 2 had the least social dysfunction. Type 3 had the highest educational attainment, genetic liability to internalizing disorders, and proportion of women. All types significantly aggregated in affected pairs of relatives. Meaningful and reproducible subtypes of AUD, consistent with prior typological results, can be obtained from national registry-based samples. Using a range of external validators and patterns of familial aggregation, our results suggest that our three-class solution captured a meaningful proportion of the clinical heterogeneity of AUD.

Deconstructing the heterogeneity of alcohol use disorder: lifetime comorbid non-alcohol substance use disorder as a distinct behavioral phenotype?

Alcohol use disorder (AUD) is an etiologically and clinically heterogeneous condition. Accumulating evidence suggests that persons with lifetime histories of comorbid AUD and non-alcohol substance use disorder (DRUG) constitute an important subgroup of AUD. This study evaluated the distinctiveness of the comorbid AUD/DRUG behavioral phenotype in a community sample with respect to risk factors, AUD course features, and outcome variables assessed at age 30. Contrast groups included persons with histories of AUD only, DRUG only, and neither AUD nor DRUG. This research utilized a prospective study design with an age-based cohort (n = 732). Participants completed four comprehensive diagnostic evaluations during the high-risk periods of adolescence, emerging adulthood, and young adulthood. The comorbid AUD/DRUG group was distinguished from the AUD only group by risk factors, AUD course features, and outcomes. Group differences in outcomes were also explained by overall substance use disorder (SUD) severity. Persons with AUD/DRUG comorbidity were indistinguishable from those with DRUG only histories with respect to risk factors and outcomes but demonstrated greater overall SUD severity. Persons with AUD only were indistinguishable from those with neither AUD nor DRUG histories in risk factor endorsements and were mostly similar in outcomes. Findings collectively suggest that young adults with histories of AUD only and those with comorbid AUD/DRUG are drawn from dissimilar populations. Similarities between the AUD only group with those absent AUD or DRUG histories are likely related to the former group's developmentally limited AUD course accompanied by relatively few or short-lived alcohol-related problems.

Associations between specific sleep and circadian characteristics and alcohol use disorder criteria and problems

Given the significant heterogeneity of alcohol use disorder (AUD) and the increasing priority to understand individual profiles of AUD, pursuing symptom-level examinations of AUD is important. Disturbances in sleep and circadian rhythms have demonstrated robust associations with alcohol consumption and AUD, yet little research has examined these associations at the symptom- or problem-levels and research to date has focused on one or two sleep/circadian characteristics. We sought to investigate the associations between (a) specific AUD symptoms and (b) domains of alcohol-related problems, and multiple sleep characteristics, collected at a daily level in the naturalistic environment. Young adult drinkers were recruited from the community (N = 159, Mage = 23.9, 58.5% female, 6.3% Asian, 35.9% Black or African American, 51.6% White, 5.0% multiracial) and completed a baseline visit as well as up to 18 days of naturalistic assessment. Several sleep/circadian characteristics, including eveningness, later midsleep timing, and shorter total sleep time, were consistently associated with the hazardous use symptom, above and beyond alcohol consumption. Eveningness (beta[SE] = 0.21[0.00], p <.01) was a significant predictor of the alcohol-related problem domain of role interference. Exploratory analyses did not find significant associations between sleep/circadian characteristics and cannabis-related problems. The relationship between sleep/circadian characteristics and AUD and related problems may be driven by a narrower set of symptoms, such as hazardous use and role interference. This may be due to shared mechanistic dysfunction in domains such as reward processing or cognitive control. Thus, these alcohol-related symptoms and problems may be addressed through transdiagnostic treatment approaches that target these underlying mechanisms.

A Longitudinal Mediation Model of Negative Emotionality, Coping Motives and Drinking Intensity Among Individuals Receiving Community Treatment for Alcohol Use Disorder.

Negative emotionality is a key domain in frameworks measuring heterogeneity in alcohol use disorder (AUD), such as the Addictions Neuroclinical Assessment (ANA). Recent research has examined the construct validity of the ANA negative emotionality domain, but has not examined whether this domain demonstrates predictive validity for drinking outcomes. In this study, we examined the association between self-reported negative emotionality at baseline and drinking intensity 1 year following AUD treatment initiation. We also assessed whether coping motives for alcohol use at 6months following treatment initiation and changes in coping motives mediated this association. This was a secondary data analysis of a multisite prospective study of individuals entering AUD treatment (n=263; 61.6% male; mean age=33.8). Measures of coping motives and drinking intensity captured those who experienced a lapse to drinking. The associations between the ANA negative emotionality domain, coping motives and drinking intensity over time were assessed using a latent growth curve mediation model. The ANA negative emotionality domain at baseline was indirectly associated with greater 7-12-month drinking intensity through higher coping motives at 6 months. Negative emotionality was not related to change in coping motives over the assessment period and change in coping motives was not related to 7-12-month drinking intensity. This analysis provides evidence for the predictive validity of the ANA negative emotionality domain for coping motives and drinking intensity among treatment seekers who experienced a lapse to drinking. Coping motives may be an important target in AUD treatment among those high in negative emotionality.

Heterogeneity in DSM-5 Symptom Criteria: Phenotypes of Alcohol Use Disorder in a Sample Seeking Alcohol Treatment.

This study sought to identify phenotypic variations among individuals with alcohol use disorder (AUD) that may, in part, help improve the effectiveness of existing AUD interventions. Latent class analysis was conducted to examine the potential heterogeneity of AUD in a sample (N=220; Mage=51.19years, standard deviation=9.94; 37.7% female) of treatment-seeking participants diagnosed with AUD using DSM-5 criteria. Three distinct patterns of responses to the 11 DSM-5 AUD symptoms emerged: Class 1 (n=114, 51.8%), Class 2 (n=78, 35.5%) and Class 3 (n=28, 12.7%). The identified profiles were further differentiated by demographics, alcohol-related constructs, individual difference characteristics and diagnostic and treatment variables. The findings have implications for refining AUD assessment as well as optimizing personalized treatment.

The Association Between Impulsivity and Relapse in Patients With Alcohol Use Disorder: A Literature Review.

Impulsivity has been identified as a key relapse risk factor in patients with alcohol use disorder (AUD); however, the inherent characteristics of this relationship have been largely understudied. The heterogeneity of AUD and variation in impulsivity constructs require careful consideration to inform future work examining the relationship. This study sought to review empirical findings examining facets of impulsivity and AUD relapse. A systematic search strategy was employed to capture studies on impulsivity measures related to AUD relapse. Impulsivity measures were qualitatively organized in terms of 'trait impulsivity'-typically measured by self-report questionnaires-and 'behavioural impulsivity', i.e. 'motor impulsivity', 'impulsive choice' and 'reflection impulsivity, assessed with cognitive-behavioural tasks. Seventeen peer-reviewed papers were identified. Relapse outcomes varied substantially in relation to impulsivity measures. Twelve papers included aspects of 'trait impulsivity', and nine studies included 'behavioural impulsivity' measures, from which five studies dealt with the 'impulsive choice' subcategory. The Barratt Impulsivity Scale was the self-report questionnaire that was most frequently used. All three included facets of impulsivity ('trait-, motor- and impulsive choice impulsivity') were associated with AUD relapse, but none seemed to be superior to another. This study confirmed that research on the relation between impulsivity and AUD relapse is relatively scarce. Future research and treatment options are proposed.

Heterogeneity of Executive Function Abilities in Recently Detoxified Patients with Alcohol Use Disorder: Evidence from a Cluster Analysis.

Impairments of executive functions (EF) have been consistently reported in patients with alcohol use disorder (AUD), mostly in studies which were based on comparisons of means between groups. However, given the high heterogeneity in AUD patients, this approach could actually cover a wide range of EF patterns. In the present study, we addressed the paucity of the literature about cognitive heterogeneity in AUD by applying a cluster analytical approach on EF measures. Seventy-eight withdrawn AUD patients and 77 healthy Control participants completed measures targeting a variety of EF components. We then used cluster analysis to identify subgroups of AUD patients. Furthermore, the AUD subgroups were compared to the Control group to establish their specific EF patterns. Findings showed that AUD patients could be divided into 3 clusters based on their EF performances. A first cluster accounting for half of the AUD sample was characterized by unimpaired EF (Cluster 1). The 2 other clusters displayed major EF deficits but differed regarding the deficient EF component. While Cluster 2 was mainly impaired on measures of rule deduction and mental flexibility, Cluster 3 was mainly characterized by a lower processing speed and impaired inhibition of an ongoing motor response. Differences in EF performances of AUD patients could be related to differences in premorbid cognitive reserve, impulsiveness patterns, and withdrawal complications. This study highlights the importance of the cognitive heterogeneity in AUD by showing that AUD patients display substantially different EF patterns. Future studies should try to go beyond mere group comparisons to further deepen our understanding about cognitive differences between AUD patients. In the long run, this could lead to more personalized prevention and treatment programs specifically tailored to the patient's impairments.

The Addictions Neuroclinical Assessment Negative Emotionality Domain Among Treatment-Seekers with Alcohol Use Disorder: Construct Validity and Measurement Invariance.

The Addictions Neuroclinical Assessment (ANA), a framework for measuring heterogeneity in alcohol use disorder (AUD), focuses on 3 domains that reflect neurobiological dysfunction in addiction and correspond to the cycles of addiction: executive function, incentive salience, and negative emotionality. Kwako and colleagues (Am J Psychiatry 176:744, 2019) validated a 3-factor model of the ANA with neuropsychological and self-report indicators among treatment-seekers and non-treatment-seekers with and without AUD. The present analysis replicated and extended these findings in a treatment-seeking sample, focusing on the negative emotionality domain. Participants (n=563; 58.8% male; mean age=34.3) were part of a multisite prospective study of individuals entering AUD treatment. We examined the factor structure of the negative emotionality domain at the baseline, 6-month follow-up, and 12-month follow-up assessments. The Beck Depression Inventory, Beck Anxiety Inventory, State-Trait Anger Expression Inventory-Trait Anger Subscale, and 3 Drinker Inventory of Consequences items assessing negative affective consequences were indicators in the model. Results indicated that a 1-factor model was an excellent fit at all assessments and that the negative emotionalitydomain was time and gender invariant. Furthermore, negative emotionality was associated with drinking patterns and reasons for alcohol use (i.e., drinking because of negative emotions and urges/withdrawal) at all assessments. This analysis provides evidence for the construct validity and measurement invariance of the ANA negative emotionality domain among AUD treatment-seekers. Future studies are needed to evaluate prospective associations between negative emotionality and specific treatment modalities, and whether individuals with greater negative emotionality are more likely to respond to treatment that targets drinking to relieve negative affective states.

Heterogeneity of alcohol use disorder: understanding mechanisms to advance personalized treatment.

Heterogeneity of alcohol use disorder: understanding mechanisms to advance personalized treatment.