Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis
Authors: Penzel Nora , Antonucci Linda A. , Betz Linda T. , Sanfelici Rachele , Weiske Johanna , Pogarell Oliver , Cumming Paul , Quednow Boris B. , Howes Oliver , Falkai Peter , Upthegrove Rachel , Bertolino Alessandro , Borgwardt Stefan , Brambilla Paolo , Lencer Rebekka , Meisenzahl Eva , Rosen Marlene , Haidl Theresa , Kambeitz-Ilankovic Lana , Ruhrmann Stephan , Salokangas Raimo R. K. , Pantelis Christos , Wood Stephen J. , Koutsouleris Nikolaos , Kambeitz Joseph ,   the PRONIA Consortium, Koutsouleris Nikolaos , Kambeitz-Ilankovic Lana , Sen Dong Mark , Erkens Anne , Gussmann Eva , Haas Shalaila , Hasan Alkomiet , Hoff Claudius , Khanyaree Ifrah , Melo Aylin , Muckenhuber-Sternbauer Susanna , Kohler Janis , Ozturk Omer Faruk , Popovic David , Rangnick Adrian , von Saldern Sebastian , Sanfelici Rachele , Spangemacher Moritz , Tupac Ana , Urquijo Maria Fernanda , Weiske Johanna , Wosgien Antonia , Kambeitz Joseph , Ruhrmann Stephan , Rosen Marlene , Betz Linda , Haidl Theresa , Blume Karsten , Seves Mauro , Kaiser Nathalie , Penzel Nora , Pilgram Tanja , Lichtenstein Thorsten , Wenzel Julian , Woopen Christiane , Borgwardt Stefan , Andreou Christina , Egloff Laura , Harrisberger Fabienne , Lenz Claudia , Leanza Letizia , Mackintosh Amatya , Smieskova Renata , Studerus Erich , Walter Anna , Widmayer Sonja , Upthegrove Rachel , Wood Stephen J. , Chisholm Katharine , Day Chris , Griffiths Sian Lowri , Iqbal Mariam , Pelton Mirabel , Mallikarjun Pavan , Stainton Alexandra , Lin Ashleigh , Salokangas Raimo K. R. , Denissoff Alexander , Ellila Anu , From Tiina , Heinimaa Markus , Ilonen Tuula , Jalo Paivi , Laurikainen Heikki , Lehtinen Maarit , Luutonen Antti , Makela Akseli , Paju Janina , Pesonen Henri , Armio Reetta-Liina , Sormunen Elina , Toivonen Anna , Turtonen Otto , Solana Ana Beatriz , Abraham Manuela , Hehn Nicolas , Schirmer Timo , Brambilla Paolo , Altamura Carlo , Belleri Marika , Bottinelli Francesca , Ferro Adele , Re Marta , Monzani Emiliano , Percudani Mauro , Sberna Maurizio , D’Agostino Armando , Del Fabro Lorenzo , Perna Giampaolo , Nobile Maria , Alciati Alessandra , Balestrieri Matteo , Bonivento Carolina , Cabras Giuseppe , Fabbro Franco , Garzitto Marco , Piccin Sara , Bertolino Alessandro , Blasi Giuseppe , Antonucci Linda A. , Pergola Giulio , Caforio Grazia , Faio Leonardo , Quarto Tiziana , Gelao Barbara , Romano Raffaella , Andriola Ileana , Falsetti Andrea , Barone Marina , Passatiore Roberta , Sangiuliano Marina , Lencer Rebekka , Surman Marian , Bienek Olga , Romer Georg , Dannlowski Udo , Meisenzahl Eva , Schultze-Lutter Frauke , Schmidt-Kraepelin Christian , Neufang Susanne , Korda Alexandra , Rohner Henrik 
Published: March 2021

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.