Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study

Yann Chye, Scott Mackey, Boris A. Gutman, Christopher R. K. Ching, Albert Batalla, Sara Blaine, Samantha Brooks, Elisabeth C. Caparelli, Janna Cousijn, Alain Dagher, John J. Foxe, Anna E. Goudriaan, Robert Hester, Kent Hutchison, Neda Jahanshad, Anne M. Kaag, Ozlem Korucuoglu, Chiang-Shan R. Li, Edythe D. London, Valentina LorenzettiMaartje Luijten, Rocio Martin-Santos, Shashwath A. Meda, Reza Momenan, Angelica Morales, Catherine Orr, Martin P. Paulus, Godfrey Pearlson, Liesbeth Reneman, Lianne Schmaal, Rajita Sinha, Nadia Solowij, Dan J. Stein, Elliot A. Stein, Deborah Tang, Anne Uhlmann, Ruth van Holst, Dick J. Veltman, Antonio Verdejo-Garcia, Reinout W. Wiers, Murat Yuecel, Paul M. Thompson, Patricia Conrod, Hugh Garavan

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While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics—the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)—that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Original languageEnglish
Article numbere12830
Pages (from-to)1-15
Number of pages15
JournalAddiction Biology
Issue number6
Early online date20 Nov 2019
Publication statusPublished - Nov 2020


FundersFunder number
Australian Medical Research Future Fund1117188, MRF1141214
Clive and Vera Ramaciotti Foundation for Biomedical Research
NIH National Center for Research Resources31160004, R01‐AA013892, UL1‐RR24925‐01
NWO‐ZonMw VIDI453.08.001, F30 DA021961, MOI‐RR‐00865, DA024853, 91713354, DA15179, DA022539
Netherlands Organization for Health Research and Development
Netherlands Organization for Scientific Research
National Institutes of HealthU54EB020403
National Institute of Mental HealthR01 DA018307, AA016599, R01 DA020709, AA19036
National Institute on Drug AbuseR01DA023248, 91676084, K25DA040032, R01‐DA014100
National Institute on Alcohol Abuse and AlcoholismR01AA013892, T32 DA024635, R01AA021449, ZIA AA000125–04
National Institute on AgingT32AG058507
University of California, Los Angeles
Marjorie M. Greene Trust
Philip Morris InternationalT32 DA 024635, 016.08.322, T32 MH17140, 20063287
Australian Government
Canadian Institutes of Health Research
Australian Research CouncilFT110100752
National Health and Medical Research Council459111
South African Medical Research Council
Monash University
ZonMw40‐00812‐98‐11002, 31180002, 31160003, PL31‐1DA024859‐01
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Department of Industry, Innovation and Science, Australian Government


    • addiction
    • structural MRI
    • substance dependence


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