The Effects of Alcohol and Cannabis Use on the Cortical Thickness of Cognitive Control and Salience Brain Networks in Emerging Adulthood: A Co-twin Control Study

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Background: Impairments in inhibitory control and its underlying brain networks (control/salience areas) are associated with substance misuse. Research often assumes a causal substance exposure effect on brain structure. This assumption remains largely untested, and other factors (e.g., familial risk) may confound exposure effects. We leveraged a genetically informative sample of twins aged 24 years and a quasi-experimental co-twin control design to separate alcohol or cannabis exposure effects during emerging adulthood from familial risk on control/salience network cortical thickness. Methods: In a population-based sample of 436 twins aged 24 years, dimensional measures of alcohol and cannabis use (e.g., frequency, density, quantity, intoxications) across emerging adulthood were assessed. Cortical thickness of control/salience network areas were assessed using magnetic resonance imaging and defined by a fine-grained cortical atlas. Results: Greater alcohol, but not cannabis, misuse was associated with reduced thickness of prefrontal (e.g., dorso/ventrolateral, right frontal operculum) and frontal medial cortices, as well as temporal lobe, intraparietal sulcus, insula, parietal operculum, precuneus, and parietal medial areas. Effects were predominately (pre)frontal and right lateralized. Co-twin control analyses suggested that the effects likely reflect both the familial predisposition to misuse alcohol and, specifically for lateral prefrontal, frontal/parietal medial, and right frontal operculum, an alcohol exposure effect. Conclusions: This study provides novel evidence that alcohol-related reductions in cortical thickness of control/salience brain networks likely represent the effects of alcohol exposure and premorbid characteristics of the genetic predisposition to misuse alcohol. The dual effects of these two alcohol-related causal influences have important and complementary implications regarding public health and prevention efforts to curb youth drinking.

Original languageEnglish (US)
Pages (from-to)1012-1022
Number of pages11
JournalBiological psychiatry
Issue number10
Early online dateJan 20 2021
StatePublished - May 15 2021

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health Grant Nos. R01 DA036216 (to WGI), R21 AA026919 (to SMM), K01 DA037280 (to SW), and R21 AA026632 (to SW). JH was supported by the National Science Foundation Graduate Research Fellowship under Grant No. 00039202, University of Minnesota Eva O. Miller Fellowship, and the National Institute on Drug Abuse of the National Institutes of Health under Award No. T32DA037183. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This report is based on work completed by JH in partial fulfillment of the requirements for the degree of Doctor of Philosophy, under the supervision of WGI. We acknowledge the Minnesota Supercomputing Institute ( and the Center for Magnetic Resonance Research (supported by Grant Nos. NIBIB P41 EB027061 and 1S10OD017974-01) at the University of Minnesota for providing resources that contributed to the research results reported within this article. We thank the four anonymous reviewers for their helpful comments on an earlier version of this article. Finally, we extend our gratitude to the twins for their participation in our studies. The authors report no biomedical financial interests or potential conflicts of interest.

Publisher Copyright:
© 2021 Society of Biological Psychiatry


  • Alcohol
  • Cannabis
  • Co-twin control
  • Control network
  • Cortical thickness
  • Salience network


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