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 Ruhrmann, Raimo K. R. Salokangas, Christos Pantelis, Stephen J. Wood, Nikolaos Koutsouleris, Joseph Kambeitz, Nikolaos Koutsouleris, Lana Kambeitz‐Ilankovic, Mark Sen Dong, Anne Erkens, Eva Gussmann, Shalaila S. Haas, Alkomiet Hasan, Claudius Hoff, Ifrah Khanyaree, Aylin Melo, Susanna Muckenhuber-Sternbauer, Janis Köhler, Ömer Öztürk, David Popovic, Adrian Rangnick, Sebastian von Saldern, Rachele Sanfelici, Moritz Spangemacher, Ana Tupac, María Fernanda Urquijo, Johanna Weiske, Antonia Wosgien, Joseph Kambeitz, Stephan Ruhrmann, Marlene Rosen, Linda T. Betz, Theresa Haidl, Karsten Blume, Mauro Seves, Nathalie Kaiser, Nora Penzel, Tanja Pilgram, Theresa Lichtenstein, Julian Wenzel, Christiane Woopen, Stefan Borgwardt, Christina Andreou, Laura Egloff, Fabienne Harrisberger, Claudia Lenz, Letizia Leanza, Amatya Mackintosh, Renata Smieskova, Erich Studerus, Anna Walter, Sonja Widmayer, Rachel Upthegrove, Stephen J. Wood, Katharine Chisholm, Chris Day, Siân Lowri Griffiths, Mariam Iqbal, Mirabel Pelton, Pavan Mallikarjun, Alexandra Stainton, Ashleigh Lin, Raimo K. R. Salokangas, Alexander Denissoff, Anu Ellilä, Tiina From, Markus Heinimaa, Tuula Ilonen, Päivi Jalo, Heikki Laurikainen, Maarit Lehtinen, Antti Luutonen, Akseli Mäkela, Janina Paju, Henri Pesonen, Reetta-Liina Armio, Elina Sormunen, Anna Toivonen, Otto Turtonen, Ana Beatriz Solana, Manuela Abraham
Abstract
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.