2D:4D digit ratio and brain volumes in alcohol use disorder

Background Prenatal androgen exposure organizes the development of the brain with permanent effects on brain structure and function. The second-to-fourth digit length ratio (2D:4D) has been associated with mental illnesses, including addictive disorders, with some studies reporting sex-dependent associations. Preliminary evidence suggests that in healthy male adolescents lower 2D:4D (indicating higher prenatal androgenization) is related to lower volumes of the right anterior cingulate cortex (ACC) which has previously been linked to a higher risk of alcohol use disorder (AUD). We aimed at transferring this association into an older cohort with AUD. Further, we explored relationships between 2D:4D and brain volumes on a whole brain level. Methods We investigated 253 men and 155 women with AUD (mean age 37.31 ± 12.54 years) and associated mean of the right and left hand 2D:4D (M2D:4D = primary predictor) with brain volumes from 3 T MRI using FreeSurfer. Results We found that lower M2D:4D was associated with smaller right ACC volume in men using a pre-specified directional one-tailed test. Secondary subsegment analyses indicated this association may primarily be observed in the right caudal ACC. Exploratory analyses suggested sex- and hemisphere-stratified associations with other brain volumes, unaffected by age moderation and largely robust after adjustment for education and AUD criteria count across models examined. Discussion In line with previous findings, the results indicate that in men with AUD, lower 2D:4D ratios are associated with smaller right ACC volumes. The findings contribute to understanding brain variability in AUD.