Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group


Zhipeng Cao, University of Vermont College of Medicine
Jonatan Ottino-Gonzalez, University of Vermont College of Medicine
Renata B. Cupertino, University of Vermont College of Medicine
Nathan Schwab, University of Vermont College of Medicine
Colin Hoke, University of Vermont College of Medicine
Orr Catherine, Swinburne University of Technology
Janna Cousijn, Universiteit van Amsterdam
Alain Dagher, Institut-Hôpital Neurologique de Montréal
John J. Foxe, University of Rochester School of Medicine and Dentistry
Anna E. Goudriaan, Universiteit van Amsterdam
Robert Hester, Melbourne School of Psychological Sciences
Kent Hutchison, University of Colorado Boulder
Chiang Shan R. Li, Yale School of Medicine
Edythe D. London, David Geffen School of Medicine at UCLA
Valentina Lorenzetti, Australian Catholic University
Maartje Luijten, Radboud University Nijmegen
Rocio Martin-Santos, Universitat de Barcelona
Reza Momenan, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Martin P. Paulus, University of California, San Diego
Lianne Schmaal, ORYGEN Youth Health
Rajita Sinha, Yale School of Medicine
Zsuzsika Sjoerds, Leiden University
Nadia Solowij, University of Wollongong
Dan J. Stein, University of Cape Town
Elliot A. Stein, National Institute on Drug Abuse
Anne Uhlmann, Technische Universität Dresden
Ruth J. van Holst, Universiteit van Amsterdam
Dick J. Veltman, Universiteit van Amsterdam
Reinout W. Wiers, Universiteit van Amsterdam
Murat Yücel, Faculty of Medicine
Sheng Zhang, Yale School of Medicine

Publication Name

Addiction Biology


Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Open Access Status

This publication is not available as open access

Funding Number


Funding Sponsor

Nederlandse Organisatie voor Wetenschappelijk Onderzoek



Link to publisher version (DOI)