Sex-based differences across the stages of the addiction cycle among adults with severe alcohol use disorder

Phenotyping approaches aim to understand heterogeneity in alcohol use disorder (AUD) using neurofunctional domains that are critical to the development and maintenance of the disease. This study explored sex-based differences across stages of the addiction cycle among adults with severe AUD.

This secondary data analysis from the genes, addiction, and personality study includes adults who met criteria for severe AUD (lifetime). Sociodemographic, substance use history, and behavioral variables were collected via cross-sectional survey. Using the three-stage addiction cycle framework, neurofunctional-related factors were selected as proxy measures: Big Five Inventory Short Form Neuroticism Scale and DSM-5 Major Depressive Disorder (MDD) (withdrawal/negative affect), Short UPPS-P Impulsive Behavior Scale and DSM-5 AUD craving item (preoccupation/anticipation), response to alcohol during the first five times drinking, and DSM-5 AUD withdrawal item (binge/intoxication). Sex differences were assessed using Chi square tests, t-tests, and Mann-Whitney U test.

Participants (N = 5745; 34% male, 66% female) were predominately white (88%) and middle-aged (44 ± 14 years). Many reported polysubstance use (64.2%). Females were significantly more likely to have a MDD diagnosis and higher neuroticism scores than males. Females had significantly higher scores in negative urgency and lack of premeditation while males had higher sensation seeking scores. Males were more likely to have lower sensitivity to alcohol and endorse drinking to relieve withdrawal symptoms than females.

Using a sex-informed approach is critical for the development and validation of AUD phenotyping tools as well as integration of phenotyping into AUD clinical trials.