Modern nosologies (e.g., International Classification of Diseases, 11th edition [ICD-11], Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM–5]) for alcohol use disorder (AUD) and dependence prioritize reliability and clinical presentation over etiology, resulting in a diagnosis that is not always strongly grounded in basic theory and research. Within these nosologies, DSM–5 AUD is treated as a discrete, largely categorical, but graded, phenomenon, which results in additional challenges (e.g., significant phenotypic heterogeneity). Efforts to increase the compatibility between AUD diagnosis and modern conceptualizations of alcohol dependence, which describe it as dimensional and partially overlapping with other psychopathology (e.g., other substance use disorders), will inspire a stronger scientific framework and strengthen AUD’s validity. We conducted a systematic review of 144 reviews to integrate addiction constructs and theories into a comprehensive framework to identify fundamental mechanisms implicated in AUD. The product of this effort was the Etiologic, Theory-based, Ontogenetic Hierarchical Framework (ETOH Framework) of AUD mechanisms, which outlines superdomains of cognitive control, reward, and negative valence and emotionality, each of which subsume narrower, hierarchically organized components. We also outline opponent processes and self-awareness as key moderators of AUD mechanisms. In contrast with other frameworks, we recommend an increased conceptual role for negative valence and compulsion in AUD. The ETOH framework serves as a critical step toward conceptualizations of AUD as dimensional and heterogeneous. It has the potential to improve AUD assessment and aid in the development of evidence-based diagnostic measures that focus on key mechanisms in AUD, consequently facilitating precision medicine.

Modern nosologies (e.g., ICD-11, DSM-5) for alcohol use disorder (AUD) and dependence prioritize reliability and clinical presentation over etiology, resulting in a diagnosis that is not always strongly grounded in basic theory and research. Within these nosologies, DSM-5 AUD is treated as a discrete, largely categorical, but graded, phenomenon, which results in additional challenges (e.g., significant phenotypic heterogeneity). Efforts to increase the compatibility between AUD diagnosis and modern conceptualizations of alcohol dependence, which describe it as dimensional and partially overlapping with other psychopathology (e.g., other substance use disorders) will inspire a stronger scientific framework and strengthen AUD’s validity. We conducted a systematic review of 144 reviews to integrate addiction constructs and theories into a comprehensive framework with the aim of identifying fundamental mechanisms implicated in AUD. The product of this effort was the Etiologic, Theory-Based, Ontogenetic Hierarchical Framework (ETOH Framework) of AUD mechanisms, which outlines superdomains of cognitive control, reward, as well as negative valence and emotionality, each of which subsume narrower, hierarchically-organized components. We also outline opponent processes and self-awareness as key moderators of AUD mechanisms. In contrast with other frameworks, we recommend an increased conceptual role for negative valence and compulsion in AUD. The ETOH framework serves as a critical step towards conceptualizations of AUD as dimensional and heterogeneous. It has the potential to improve AUD assessment and aid in the development of evidence-based diagnostic measures that focus on key mechanisms in AUD, consequently facilitating treatment matching.