Altered cortical maturation in adolescent cannabis users with and without schizophrenia

Katherine A. Epstein, Sanjiv Kumra

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26 Scopus citations


During late adolescence, progressive cortical thinning occurs in heteromodal association cortex (HASC) that is thought to subserve cognitive development. However, the impact of cannabis use disorder (CUD) upon cortical gray matter development in both healthy adolescents and adolescents with early-onset schizophrenia (EOS) is unclear. T1-weighted magnetic resonance images were acquired from 79 adolescents at baseline and after an 18-month follow-up: 17 with EOS, 17 with CUD, 11 with EOS. +. CUD, and 34 healthy controls (HC). Mean age at baseline was 16.4. years (CUD. +) and 17.0. years (CUD-). Using FreeSurfer, measures of cortical thickness for ROIs within HASC were obtained. A 2 (EOS versus no EOS) × 2 (CUD versus no CUD) multivariate analysis of covariance was applied to change scores from baseline to follow-up to test for main effects of EOS and CUD and an interaction effect. After adjusting for covariates, a significant main effect of CUD was observed. Adolescents with CUD showed an attenuated loss of cortical thickness in the left and right supramarginal, left and right inferior parietal, right pars triangularis, left pars opercularis, left superior frontal, and left superior temporal regions compared to non-using subjects. Stepwise linear regression analysis indicated that greater cumulative cannabis exposure predicted greater cortical thickness in both the left (p = .008) and right (p = .04) superior frontal gyri at study endpoint after adjusting for baseline cortical thickness for the entire sample. These preliminary longitudinal data demonstrate an atypical pattern of cortical development in HASC in adolescents with CUD relative to non-using subjects, across diagnostic groups. Additional studies are needed to replicate these data and to clarify the clinical significance of these findings.

Original languageEnglish (US)
Pages (from-to)143-152
Number of pages10
JournalSchizophrenia Research
Issue number1-3
StatePublished - Mar 1 2015

Bibliographical note

Funding Information:
Dr. Kumra has received research support from the National Alliance for Research on Schizophrenia and Depression and Otsuka Pharmaceutical Co., Ltd., and plans to receive future research support from SyneuRx International (Taiwan) Corp. Ms. Epstein has no financial disclosures or potential conflicts of interest to report.

Funding Information:
This study was funded by the National Institute of Mental Health Grant MH073150-05 (Cannabis and Schizophrenia; to S.K.). The funding source played no role in the study design, in the collection, analysis, or interpretation of the data, in the writing of this manuscript, or in the decision to submit it for publication.

Publisher Copyright:
© 2014 Elsevier B.V.


  • Cortical
  • Critical period
  • Endocannabinoid
  • Gray matter
  • Schizophrenia
  • Structural imaging


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