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JAMA Psychiatry. 2015 Oct;72(10):1002-11. doi: 10.1001/jamapsychiatry.2015.1131.

Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence.

Author information

1
Rotman Research Institute, Baycrest, Toronto, Ontario, Canada.
2
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
3
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.
4
Department of Radiology, University of Calgary, Calgary, Alberta, Canada6Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.
5
Department of Health Sciences, University of Quebec in Chicoutimi, Chicoutimi, Quebec, Canada.
6
Department of Psychiatry and Centre de Recherche du Centre Hospitalier Universitaire Ste-Justine, University de Montréal, Montreal, Quebec, Canada.
7
School of Psychology, Cardiff University, Cardiff, Wales.
8
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.
9
Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
10
Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neurosciences, Trinity College, Dublin, Ireland.
11
Institut für Systemische Neurowissenschaften, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
12
Physikalisch-Technische Bundesanstalt, Berlin, Germany.
13
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.
14
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.
15
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
16
Neurospin, CEA-Saclay Center, Paris, France.
17
Department of Psychiatry, University of Vermont, Burlington24Department of Psychology, University of Vermont, Burlington.
18
School of Physics and Astronomy, University of Nottingham, Nottingham, England.
19
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany.
20
Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
21
Department of Psychology, University College Dublin, Dublin, Ireland.
22
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, England.
23
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.
24
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.

Abstract

IMPORTANCE:

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.

DESIGN, SETTING, AND PARTICIPANTS:

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.

MAIN OUTCOMES AND MEASURES:

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 AND RELEVANCE:

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.

Comment in

PMID:
26308966
PMCID:
PMC5075969
DOI:
10.1001/jamapsychiatry.2015.1131
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosures: Dr Banaschewski served in an advisory or consultancy role for Hexal Pharma, Lilly, Medice, Novartis, Otsuka, Oxford outcomes, PCM scientific, Shire, and Viforpharma; has received conference attendance support and conference support or speaker’s fees from Lilly, Medice, Novartis, and Shire; and has been involved in clinical trials conducted by Lilly, Shire, and Viforpharma. The present work is unrelated to these grants and relationships. Dr Paus is the Tanenbaum Chair in Population Neuroscience at the Rotman Research Institute. No other disclosures were reported.

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