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

Nora Penzel, Linda A Antonucci, Linda T 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-Ilankovic, Stephan RuhrmannRaimo R K Salokangas, Christos Pantelis, Stephen J Wood, Nikolaos Koutsouleris, Joseph Kambeitz, PRONIA Consortium

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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)1-10
Issue number00
Publication statusPublished - 3 Mar 2021

Bibliographical note

The CIP study is a DFG-funded project (grant agreement No. KA 4413/1-1). The PRONIA study is a European Collaboration Project funded under the 7th Framework Program under grant agreement no 602152. RU reports grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion, outside the submitted work. NK and RS received honoraria for talks presented at education meetings organized by Otsuka/Lundbeck. CP participated in advisory boards for Janssen-Cilag, AstraZeneca, Lundbeck, and Servier and received honoraria for talks presented at educational meetings organized by AstraZeneca, Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck, and Shire. CP acknowledges support by an Australian National Health & Medical Research Council (NHMRC) Senior Principal Research Fellowship (ID: 1105825), a NHMRC Program Grant (ID: 1150083). All other authors report no biomedical financial interests or potential competing interests. Open Access funding enabled and organized by Projekt DEAL.

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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