Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis

Eleonora Maggioni, Maria G Rossetti, Nicholas B Allen, Albert Batalla, Marcella Bellani, Yann Chye, Janna Cousijn, Anna E Goudriaan, Robert Hester, Kent Hutchison, Chiang-Shan R Li, Rocio Martin-Santos, Reza Momenan, Rajita Sinha, Lianne Schmaal, Nadia Solowij, Chao Suo, Ruth J van Holst, Dick J Veltman, Murat YücelPaul M Thompson, Patricia Conrod, Scott Mackey, Hugh Garavan, Paolo Brambilla, Valentina Lorenzetti

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.

Original languageEnglish
Pages (from-to)4652-4666
Number of pages15
JournalHuman Brain Mapping
Issue number13
Early online date12 Jul 2023
Publication statusE-pub ahead of print - 12 Jul 2023

Bibliographical note

Funding Information:
The study was partly supported by the ENIGMA Addiction R01 funding NIH/NIDA R01DA047119 and by the Italian Ministry of Health (Ricerca Corrente 2023). Dr. Eleonora Maggioni was partly supported by the Italian Ministry of Health (GR‐2019‐12370616) and by the BIAL Foundation (BIAL Foundation Grant Programme 2020/21, no. 288/2020). Dr. Dick Veltman received funding from the Netherlands Organization for Health Research and Development (ZonMW) grant 31160004 from NWO. Drs. Anna E. Goudriaan and Ruth J. van Holst received funding from ZonMW grant 91676084 from NWO. Drs. Janna Cousijn and Anna E. Goudriaan received funding for the Cannabis Prospective study from ZonMW grant 31180002 from NWO. Dr. Reza Momenan was supported by the Intramural Clinical and Biological Research Program of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Dr. Rajita Sinha received funds from NIDA (PL30‐1DA024859‐01), the NIH National Center for Research Resources (UL1‐RR24925‐01), and NIAAA (R01‐AA013892). Dr. Nadia Solowij received funding from the Clive and Vera Ramaciotti Foundation for Biomedical Research, and National and Health and Medical Research Council Project grant 459111 and was supported by Australian Research Council Future Fellowship FT110100752. Prof. Murat Yücel was supported by National Health and Medical Research Council Fellowship #1117188 and the David Winston Turner Endowment Fund. Dr Valentina Lorenzetti was supported by The Australian Catholic University through a competitive scheme.

Publisher Copyright:
© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

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