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.

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Publication Details

Journal
European Archives of Psychiatry and Clinical Neuroscience
Published
2026-09-04
DOI
https://doi.org/10.1007/s00406-026-02363-2
Primary Topic
Sexual Differentiation and Disorders
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article
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article

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

Andreas Heinz, Jens Strehle, Johannes Steffen, Mathieu Pinger et al.
European Archives of Psychiatry and Clinical Neuroscience
Sexual Differentiation and Disorders
article

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

Andreas Heinz, Jens Strehle, Johannes Steffen, Mathieu Pinger, Maria Garbusow, Charlotte M. Grosskopf, Sabine Vollstädt‐Klein, Franziska Weiß, Michael Marxen, Gesine Wieder, Alvaro Aguilera, Kristina Schwarz, Friederike Wedemeyer, Tanja Endraß, Angela Hentschel, Damian Karl, Wolfgang E. Nagel, Marie Heigert, Carlotta Riemerschmid, Ann‐Kathrin Stock, Claudia Ebrahimi, Herta Flor, Sarah Gerhardt, Sasha Frölich, Peter Kirsch, Shuyan Liu, Bernd Lenz, Falk Kiefer, Marvin Ganz, Sarah Schwöbel, Viktoria Arndt, Andreas Ströhle, Judith Zaiser, Alfred Wieland, Gabriela Gan, Felix Bermpohl, Christian Beste, Acelya Aslan, Rafat Boroumand-Jazi, Clemens Kirschbaum, Patricia Pelz, Pascale C. Fischbach, Filippo Ghin, Annika Rosenthal, Nina Romanczuk-Seiferth, Henrik Walter, C. Heim, Stefanie Kunas, Sina Vetter, Stefan Kiebel, Hao Chen, Tobias Banaschewski, Roshan Rane, Marcella Rietschel, Patrick Bach, Matthew Belanger, Matthias Reichl, Michael A. Rapp, Michael N. Smolka, Kerstin Ritter, Julia Wenzel, Nadja S. Bahr, Heiner Stuke, Maximilian Pilhatsch
article en

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.

European Archives of Psychiatry and Clinical Neuroscience
University of Potsdam (DE), Heidelberg University (DE), North-West University (ZA), University Hospital Heidelberg (DE), Humboldt-Universität zu Berlin (DE), Central Institute of Mental Health (DE), German Center for Infection Research (DE), German Centre for Cardiovascular Research (DE), Hertie Institute for Clinical Brain Research (DE), Technische Universität Dresden (DE), University of Tübingen (DE)
Good health and well-being
Openalex Percentile: Top 18%
Sexual Differentiation and Disorders
DOIOpen Access PDFOpenAlex
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