Towards an integrative transdisciplinary framework for understanding the etiopathogenesis of problematic drinking : insights from deep phenotyping and network modeling for personalized prevention
Authors:   , Martins Jorge S. 
Published: August 2021

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Background and Significance. Decades of research have consistently suggested that persistent problematic drinking is an etiologically heterogeneous condition. This heterogeneity has been proposed as an explanation for why current general prevention and intervention efforts are still largely ineffective. Therefore, understanding this existing heterogeneity seems crucial for developing more effective prevention and intervention efforts aimed at reducing harmful and hazardous drinking. Specific Aims. The current study aimed to (Aim 1) determine the unique and specific effects of seven functional domains (Incentive Salience/Craving, Alcohol Sensitivity, Negative Emotionality, Alcohol Withdrawal, Executive Functions, Risk Propensity, and Self-Control/Disinhibition) on alcohol use and related experiences, including harmful and hazardous drinking; (Aim 2) determine the classification utility of varying combinations of functional domains in discriminating individuals at risk for harmful and hazardous drinking; (Aim 3) identify common profiles of the hypothesized functional domains that may either protect or place individuals at higher risk and explore their group-specific etiological relevance for harmful and hazardous drinking; (Aim 4) identify the most "central" or influential domains for the emergence, development, and maintenance of persistent harmful and hazardous drinking. Methods. The current study included data from 552 emerging and young adults, who completed an assessment battery consisting of self-report and behavioral task measures that provided demographic and personal history information, alcohol use and related experiences, and estimates of core neurocognitive abilities pertaining to the hypothesized functional domains. Results. Results indicated that the functional domains were differentially associated with measures of alcohol use and related experiences and failed to consistently show robust associations with all alcohol-related measures, when tested simultaneously. Nevertheless, Incentive Salience/Craving, Alcohol Sensitivity, Alcohol Withdrawal, and Self-Control/Disinhibition showed expected unique associations with most drinking measures, whereas Negative Emotionality showed a handful of unexpected negative associations. Results also indicated that the combination of Incentive Salience/Craving, Alcohol Withdrawal, and Alcohol Sensitivity produced the single most parsimonious and optimal combination with the best classification utility in discriminating individuals at risk for harmful and hazardous drinking. Furthermore, even though Alcohol Withdrawal and Alcohol Sensitivity produced an acceptable classification precision, Incentive Salience/Craving demonstrated by far the strongest predictive utility and diagnostic value. Results from mixture modeling identified three homogeneous and well-separated classes characterized by distinct underlying risk profiles of neurocognitive abilities pertaining to the functional domains, as well as unique patterns of alcohol use and related experiences: Low Risk/Light Drinkers-Abstainers (n = 116, 21 [percent]); Moderate Risk/Social Drinkers (n = 231, 42 [percent]); and High Risk/Problem Drinkers (n = 205, 37 [percent]). Finally, Self-Control/Disinhibition was consistently identified as the most interconnected and highly central domain, whereas Alcohol Sensitivity was weakly interconnected in all class-specific network configurations. No significant differences were found in either local or global connectivity of the class-specific network architectures. Conclusion. Taken all together, the current results contribute to enhance our understanding of the relative importance of etiologically relevant alcohol-specific and transdiagnostic domains for persistent problematic drinking. Theoretical insights for understanding of the etiological heterogeneity of harmful and hazardous drinking, as well as practical implications for personalized prevention of persistent problematic drinking are discussed.