title: Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence.
abstract: OBJECTIVE
  Cannabis use during adolescence is known to increase the risk for schizophrenia in men. Sex differences in the dynamics of brain maturation during adolescence may be of particular importance with regard to vulnerability of the male brain to cannabis exposure.
  
  
  OBJECTIVE
  To evaluate whether the association between cannabis use and cortical maturation in adolescents is moderated by a polygenic risk score for schizophrenia.
  
  
  METHODS
  Observation of 3 population-based samples included initial analysis in 1024 adolescents of both sexes from the Canadian Saguenay Youth Study (SYS) and follow-up in 426 adolescents of both sexes from the IMAGEN Study from 8 European cities and 504 male youth from the Avon Longitudinal Study of Parents and Children (ALSPAC) based in England. A total of 1577 participants (aged 12-21 years; 899 [57.0%] male) had (1) information about cannabis use; (2) imaging studies of the brain; and (3) a polygenic risk score for schizophrenia across 108 genetic loci identified by the Psychiatric Genomics Consortium. Data analysis was performed from March 1 through December 31, 2014.
  
  
  METHODS
  Cortical thickness derived from T1-weighted magnetic resonance images. Linear regression tests were used to assess the relationships between cannabis use, cortical thickness, and risk score.
  
  
  RESULTS
  Across the 3 samples of 1574 participants, a negative association was observed between cannabis use in early adolescence and cortical thickness in male participants with a high polygenic risk score. This observation was not the case for low-risk male participants or for the low- or high-risk female participants. Thus, in SYS male participants, cannabis use interacted with risk score vis-à-vis cortical thickness (P = .009); higher scores were associated with lower thickness only in males who used cannabis. Similarly, in the IMAGEN male participants, cannabis use interacted with increased risk score vis-à-vis a change in decreasing cortical thickness from 14.5 to 18.5 years of age (t137 = -2.36; P = .02). Finally, in the ALSPAC high-risk group of male participants, those who used cannabis most frequently (≥61 occasions) had lower cortical thickness than those who never used cannabis (difference in cortical thickness, 0.07 [95% CI, 0.01-0.12]; P = .02) and those with light use (<5 occasions) (difference in cortical thickness, 0.11 [95% CI, 0.03-0.18]; P = .004).
  
  
  CONCLUSIONS
  Cannabis use in early adolescence moderates the association between the genetic risk for schizophrenia and cortical maturation among male individuals. This finding implicates processes underlying cortical maturation in mediating the link between cannabis use and liability to schizophrenia.
authors: Rotman Research Institute, Baycrest, Toronto, Ontario, Canada.
authors: Leon
authors: L
authors: French
authors: Rotman Research Institute, Baycrest, Toronto, Ontario, Canada.
authors: Courtney
authors: C
authors: Gray
authors: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors: Gabriel
authors: G
authors: Leonard
authors: Groupe d'Étude des Conditions de vie et des Besoins de la Population, Cégep de Jonquiere, Jonquiere, Saguenay, Quebec, Canada 4Department of Human Sciences, University of Quebec in Chicoutimi, Chicoutimi, Quebec, Canada.
authors: Michel
authors: M
authors: Perron
authors: Department of Radiology, University of Calgary, Calgary, Alberta, Canada6Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.
authors: G Bruce
authors: GB
authors: Pike
authors: Department of Health Sciences, University of Quebec in Chicoutimi, Chicoutimi, Quebec, Canada.
authors: Louis
authors: L
authors: Richer
authors: Department of Psychiatry and Centre de Recherche du Centre Hospitalier Universitaire Ste-Justine, University de Montréal, Montreal, Quebec, Canada.
authors: Jean R
authors: JR
authors: Séguin
authors: Groupe d'Étude des Conditions de vie et des Besoins de la Population, Cégep de Jonquiere, Jonquiere, Saguenay, Quebec, Canada 4Department of Human Sciences, University of Quebec in Chicoutimi, Chicoutimi, Quebec, Canada.
authors: Suzanne
authors: S
authors: Veillette
authors: School of Psychology, Cardiff University, Cardiff, Wales.
authors: C John
authors: CJ
authors: Evans
authors: Institut National de la Santé et de la Recherche Medicale (INSERM), Unité Mixte de Recherche (UMR) 1000, Research Unit Imaging and Psychiatry, Commissariat à l'Énergie Atomique (CEA), Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Serv.
authors: Eric
authors: E
authors: Artiges
authors: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Tobias
authors: T
authors: Banaschewski
authors: Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland.
authors: Arun W L
authors: AW
authors: Bokde
authors: Institut für Systemische Neurowissenschaften, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Uli
authors: U
authors: Bromberg
authors: Physikalisch-Technische Bundesanstalt, Berlin, Germany.
authors: Ruediger
authors: R
authors: Bruehl
authors: Institut für Systemische Neurowissenschaften, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Christian
authors: C
authors: Buchel
authors: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England20Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London.
authors: Anna
authors: A
authors: Cattrell
authors: Department of Psychiatry and Centre de Recherche du Centre Hospitalier Universitaire Ste-Justine, University de Montréal, Montreal, Quebec, Canada19Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England.
authors: Patricia J
authors: PJ
authors: Conrod
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Herta
authors: H
authors: Flor
authors: Neurospin, CEA-Saclay Center, Paris, France.
authors: Vincent
authors: V
authors: Frouin
authors: Institut für Systemische Neurowissenschaften, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Jurgen
authors: J
authors: Gallinat
authors: Department of Psychiatry, University of Vermont, Burlington24Department of Psychology, University of Vermont, Burlington.
authors: Hugh
authors: H
authors: Garavan
authors: School of Physics and Astronomy, University of Nottingham, Nottingham, England.
authors: Penny
authors: P
authors: Gowland
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors: Andreas
authors: A
authors: Heinz
authors: Institut National de la Santé et de la Recherche Medicale (INSERM), Unité Mixte de Recherche (UMR) 1000, Research Unit Imaging and Psychiatry, Commissariat à l'Énergie Atomique (CEA), Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Serv.
authors: Herve
authors: H
authors: Lemaitre
authors: Institut National de la Santé et de la Recherche Medicale (INSERM), Unité Mixte de Recherche (UMR) 1000, Research Unit Imaging and Psychiatry, Commissariat à l'Énergie Atomique (CEA), Direction des Sciences du Vivant, Institut d'Imagerie Biomédicale, Serv.
authors: Jean-Luc
authors: JL
authors: Martinot
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Frauke
authors: F
authors: Nees
authors: Neurospin, CEA-Saclay Center, Paris, France.
authors: Dimitri Papadopoulos
authors: DP
authors: Orfanos
authors: Rotman Research Institute, Baycrest, Toronto, Ontario, Canada.
authors: Melissa Marie
authors: MM
authors: Pangelinan
authors: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Luise
authors: L
authors: Poustka
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Marcella
authors: M
authors: Rietschel
authors: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors: Michael N
authors: MN
authors: Smolka
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors: Henrik
authors: H
authors: Walter
authors: Department of Psychology, University College Dublin, Dublin, Ireland.
authors: Robert
authors: R
authors: Whelan
authors: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, England.
authors: Nic J
authors: NJ
authors: Timpson
authors: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England20Medical Research Council-Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London.
authors: Gunter
authors: G
authors: Schumann
authors: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, England.
authors: George Davey
authors: GD
authors: Smith
authors: Department of Physiology and Experimental Medicine, Hospital for Sick Children, University of Toronto, Ontario, Canada31Department of Physiology, University of Toronto, Ontario, Canada32Department of Nutritional Sciences, University of Toronto, Ontario, C.
authors: Zdenka
authors: Z
authors: Pausova
authors: Rotman Research Institute, Baycrest, Toronto, Ontario, Canada33Department of Psychology, University of Toronto, Ontario, Canada34Department of Psychiatry, University of Toronto, Ontario, Canada35Child Mind Institute, New York, New York.
authors: Tomáš
authors: T
authors: Paus
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D017668:Age of Onset; D001921:Brain / Q000254:growth & development; D002540:Cerebral Cortex / Q000254:growth & development*; D002648:Child; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008385:Marijuana Smoking / Q000453:epidemiology*; D011446:Prospective Studies; D018570:Risk Assessment; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult