Common Factors Underlying Diverse Responses in Alcohol Use Disorder

Abstract

Interindividual variation in responses to alcohol is substantial, posing challenges for medical management and for understanding the biological underpinnings of alcohol use disorders (AUD). It is important to understand whether diverse alcohol responses such as sedation, which is predictive of risk and partly heritable, occur concurrently or independently from responses such as blackouts and withdrawal. We hypothesized that latent factors accounting for sources of variance in diverse alcohol response phenotypes could be identified in a large, deeply phenotyped sample of patients with AUD.Methods: We factor analyzed 17 alcohol response related items from the Alcohol Dependence Scale (ADS) in 938 individuals diagnosed with AUD via structured clinical interviews. Demographic, genetic, and clinical characteristics were tested as predictors of the latent factors by multiple indicators, multiple causes analysis.Results: The final factor solution included three alcohol response factors: Physical Symptoms, Perceptual Disturbances, and Neurobiological Effects. Both gender and genetic ancestry were identified as variables influencing alcohol response. Major depressive disorder positively predicted physical symptoms and aggression negatively predicted physical symptoms. Barratt's Impulsivity Scale total score predicted the Physical and Perceptual domains. Family history, average drinks per drinking day, and negative urgency (an impulsivity measure) predicted all three domains.Conclusions: Diverse items from the ADS concurrently load onto three correlated alcohol response factors rather than loading independently. Genetic ancestry and clinical characteristics predicted the severity of items that define the alcohol response factors even after accounting for degree of alcohol consumption. Co-occurring phenotypes point towards an underlying shared physiology of diverse alcohol responses.

Leucine-Rich Repeat Kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking

“…Loss of control over alcohol drinking leads to abuse and hinders long-term abstinence, driving relapse. Epidemiological data indicates there is significant individual variability in the response to alcohol and the likelihood of developing AUD (2)(3)(4). For example, while alcohol consumption is highly prevalent among the adult U.S. population, only a fraction (~ 8%) of those who consume alcohol are diagnosed with AUD each year (5).…”

Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking

“…Loss of control over alcohol drinking leads to abuse and hinders long-term abstinence, driving relapse. Only a fraction (~8%) of those who consume alcohol are diagnosed with AUD each year [ 2 ], pointing to the existence of risk and resilience factors for developing the disorder [ 3 , 4 ]. The striatum plays a central role in learning and execution of reward-motivated behaviors, making this brain region very relevant for substance use disorders.…”