Year: 2026
Type: article
Study design: Observational Study
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.
Authors: Matthias Reichl, Bernd Lenz, Rafat Boroumand-Jazi, Patrick Bach, Tobias Banaschewski, Michael A. Rapp, Henrik Walter, Michael Marxen, Michael N. Smolka, Andreas Heinz, Falk Kiefer, Roshan Rane, Kerstin Ritter, Nadja S. Bahr, Felix Bermpohl, Claudia Ebrahimi, Maria Garbusow, Marie Heigert, Christine Heim, Stefanie Kunas, Shuyan Liu, Patricia Pelz, Carlotta Riemerschmid, Nina Romanczuk-Seiferth, Annika Rosenthal, Andreas Ströhle, Heiner Stuke, Henrik Walter, Friederike Wedemeyer, Julia Wenzel, Alvaro Aguilera, Viktoria Arndt, Matthew Belanger, Christian Beste, Hao Chen, Tanja Endraß, Pascale C. Fischbach, Sasha Frölich, Filippo Ghin, Charlotte M. Großkopf, Angela Hentschel, Stefan Kiebel, Clemens Kirschbaum, Michael Marxen, Wolfgang E. Nagel, Maximilian Pilhatsch, Johannes Steffen, Jens Strehle, Sarah Schwöbel, Ann-Kathrin Stock, Gesine Wieder, Acelya Aslan, Herta Flor, Gabriela Gan, Marvin Ganz, Sarah Gerhardt, Damian Karl, Peter Kirsch, Mathieu Pinger, Marcella Rietschel, Kristina Schwarz, Sabine Vollstädt-Klein, Franziska Weiss, Alfred Wieland, Judith Zaiser, Sina Vetter
Institutions: Heidelberg University, Central Institute of Mental Health, Medizinische Fakultät Mannheim, Deutsches Zentrum für Psychische Gesundheit, University of Potsdam, University of Tübingen, Technische Universität Dresden, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité - Universitätsmedizin Berlin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,990
OpenAlex ID: W7208749502