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 Yücel, Paul M. Thompson, Patricia Conrod, Hugh Garavan

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)


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
Number of pages15
JournalAddiction Biology
Issue number6
Publication statusPublished - Nov 2020


  • addiction
  • structural MRI
  • substance dependence

Cite this