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In Pursuit of Precision Medicine: A New Framework of Alcohol Use Disorder

By Cassie L. Boness, Ph.D., Research Assistant Professor Center on Alcohol, Substance use, And Addictions, University of New Mexico


Alcohol use disorder is a significant public health problem, yet treatments demonstrate only modest efficacy. 

Because those individuals diagnosed with alcohol use disorder exhibit considerable heterogeneity in terms of clinical presentation as well as patterns of consumption, profiles of risk (e.g., family history of alcohol-related problems, age of first drink), alcohol-related consequences, and patterns of comorbid psychopathology, it is unlikely that a single treatment approach will be best for all individuals with alcohol use disorder. 

What is more likely is that specific types of alcohol use disorder symptoms, or profiles of symptoms, which are caused by dysfunction in certain neurobiological, cognitive, and psychological mechanisms, will be best addressed with personalized treatments that target that specific dysfunction (i.e., precision medicine). 

Flow chart of Alcohol Use Disorder Diagnosis in rainbow ombre colors

My colleagues and I at the University of Missouri are conducting novel work in this area. Our recent systematic review, “The Etiologic, Theory-Based, Ontogenetic Hierarchical (ETOH) Framework of Alcohol Use Disorder: A Translational Systematic Review of Reviews”, published in Psychological Bulletin (October 2021), integrates the literature on the core mechanisms that are thought to cause and maintain an alcohol use disorder. 

“We integrated constructs and theories on the causal processes, or mechanisms, that influence risk for developing and maintaining an alcohol use from 144 published reviews into the ETOH Framework. The result is a framework that organizes various finer grained mechanisms, such as incentive salience, into the broader superdomains of reward, cognitive control, and negative valence and emotionality. 

The reward superdomain broadly describes those mechanisms that transform otherwise neutral stimuli or events (e.g., cues, such as a specific location) into attractive and wanted stimuli, such as cravings and consummatory anticipation.

Cognitive control broadly describes mechanisms related to the organization of behavior towards future goals (e.g., planning), as well as compulsivity and impulsivity. 

Negative valence and emotionality broadly describe mechanisms related to negative emotions (e.g., anxiety) and other adverse effects such as those resulting from substance use (e.g., withdrawal or hangover symptoms). 

These superdomains and their lower order components are depicted in the figure accompanying this article.

We believe this framework may be useful in formulating diagnostic criteria for alcohol use disorder that are more closely related to the causes of alcohol use disorder. In comparison to the current diagnostic approach, which identifies alcohol use disorder based on psychosocial problems resulting from alcohol use, this approach may help improve the accuracy of and information provided by a diagnosis of alcohol use disorder as well as offer implications for the treatment to which they may respond.

The mechanisms identified as part of this review, at various levels of the hierarchical framework, may serve as a starting place for matching people to the treatments that are best for them. For example, we identified “cognitive control” as a major domain of relevance in alcohol use disorder. Individuals with dysregulated cognitive control, who may be more impulsive, are likely at greater risk for the development and maintenance of an alcohol use disorder. Thus, improving cognitive control in these individuals may be one viable treatment target. This, of course, is complicated by the interactions between mechanisms in the framework as well as other considerations such as whether the dysregulation in a given mechanism was premorbid (i.e., present prior to heavy and prolonged consumption) or acquired (i.e., the result of heavy and prolonged consumption). 

Although assisting in matching individuals to the best treatment for them based on their unique profile is an important long-term goal of the ETOH Framework, it is first important to test the framework empirically and then develop assessment tools to capture each of the mechanisms. Indeed, these describe the next steps in my program of research. 

In the meantime, we are hopeful that researchers can use the framework as guide for additional research that clarifies unanswered questions relevant to alcohol use disorder. For example, are some mechanisms more relevant at early versus later stages of addiction? Do the mechanisms identified here contribute equally to alcohol use disorder across individuals of diverse backgrounds and environments? To support further advancement of the ETOH Framework, we have created an open commentary space where readers can provide feedback: 


White female with blonde hair wearing a black shirt with butterfly tattoos on her armsDr. Cassie L. Boness is a Research Assistant Professor at the
Center on Alcohol, Substance use, And Addictions at the University of New Mexico.
She received her Ph.D. in Clinical Psychology from the University of Missouri in 2021.
Connect with her on Twitter @Cassie_Boness or via email at [email protected].