Eur Arch Psychiatry Clin Neurosci. 2026 Sep 4. doi: 10.1007/s00406-026-02363-2. Online ahead of print.
ABSTRACT
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.
PMID:42696133 | DOI:10.1007/s00406-026-02363-2
