Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

the PRONIA-consortium, Nora Penzel, Linda A. Antonucci, Linda Betz, Rachele Sanfelici, Johanna Weiske, Oliver Pogarell, Paul Cumming, Boris B. Quednow, Oliver Howes, Peter Falkai, Rachel Upthegrove, Alessandro Bertolino, Stefan Borgwardt, Paolo Brambilla, Rebekka Lencer, Eva Meisenzahl, Marlene Rosen, Theresa Haidl, Lana Kambeitz-IlankovicStephan Ruhrmann, Raimo R.K. Salokangas, Christos Pantelis, Stephen J. Wood, Nikolaos Koutsouleris, Joseph Kambeitz

Research output: Contribution to journalArticlepeer-review


Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.

Original languageEnglish
Pages (from-to)1484-1493
Issue number8
Publication statusPublished - 2021

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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