Specific diagnostic criteria identify those at high risk for progression from ‘preaddiction’ to severe alcohol use disorder

Importance Both current DSM-5 diagnoses of substance use disorders (SUDs) and the recent “preaddiction” conceptual proposal (i.e., mild-to-moderate SUD) rely on criterion count-based approaches, without consideration of evidence regarding varying severity grading indexed by individual criteria. Objective To examine correlates of alcohol use disorder (AUD) across count-based severity groups (i.e., mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative of greater severity, and evaluate whether the presence of specific criteria within mild-to-moderate AUD differentiates across relevant correlates and manifests in greater hazards of severe AUD development. Design Cross-sectional and longitudinal cohort study. Setting Family-based study of individuals from seven sites across the United States. Participants Cross-sectional ( N =13,110; mean [SD] age, 37.8 [14.2] years) and longitudinal cohorts ( N =2,818; mean baseline [SD] age, 16.1 [3.2] years) from the Collaborative Study on the Genetics of Alcoholism (COGA). Exposure N/A Main Outcomes and Measures Sociodemographic, alcohol-related, psychiatric comorbidity (major depressive disorder, antisocial personality disorder, and other SUDs), brain electroencephalography (EEG), and AUD polygenic score measures as correlates of DSM-5 AUD levels (i.e., mild, moderate, severe) and criterion severity-defined “preaddiction” (i.e., low-risk vs. high-risk mild-to-moderate) AUD diagnostic groups. Results Associations with alcohol-related, psychiatric, EEG, and AUD polygenic score measures reinforced the role of increasing criterion counts as indexing severity. Yet even within those meeting criteria for mild-to-moderate AUD (2-5 criteria), the presence of specific “high-risk” criteria (e.g., withdrawal) identified a group reporting heavier drinking and greater psychiatric comorbidity even after accounting for criterion count differences. In longitudinal analyses, prior mild-to-moderate AUD characterized by endorsement of at least one “high-risk” criterion outperformed other adolescent and young adult correlates of AUD progression (i.e., comorbid psychiatric diagnoses, alcohol involvement milestones) and was associated with more accelerated progression to severe AUD (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared to prior mild-to-moderate AUD without endorsement of “high-risk” criteria (aHR, 5.64; 95% CI, 3.28-9.70), independent of criterion count. Conclusions and Relevance Current count-based AUD diagnostic approaches and the “preaddiction” concept both ignore heterogeneity among criteria. Estimating addiction vulnerability by emphasizing specific “high-risk” criteria may improve our understanding of its development and focus attention on those at greatest risk. Question Does emphasis on specific alcohol use disorder (AUD) criteria improve identification of individuals at risk for developing more severe AUD? Findings Individuals meeting criteria for mild-to-moderate AUD are two-fold more likely to progress to severe AUD if they endorse criteria for drinking despite physical/psychological problems, giving up important activities, spending a great deal of time drinking, failure to fulfill major role obligations, withdrawal, and craving, even after accounting for total criterion count. Meaning Emphasis on especially severe criteria as indicators of addiction vulnerability in current diagnostic approaches may increase detection of individuals with greater likelihood for disorder progression. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement COGA is supported by NIH Grant U10AA008401 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA). Investigator effort for this study was also supported by NIDA grant T32DA015035 (APM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The current study was approved by the Institutional Review Board at Washington University School of Medicine in St. Louis. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes COGA data are available through the National Institute on Alcohol Abuse and Alcoholism or the database of Genotypes and Phenotypes (dbGaP; phs000763.v1.p1, phs000125.v1.p1). PGC alcohol dependence GWAS summary statistics may be obtained from the PGC website (). MVP GWAS summary statistics are available through dbGaP (phs001672). FinnGenR8 ICD-based AUD GWAS data were obtained from . For more information, visit .