Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence.
JAMA Psychiatry. 2015-10-01; 72(10): 1002
DOI: 10.1001/jamapsychiatry.2015.1131
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1. 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.
French L(1), Gray C(1), Leonard G(2), Perron M(3), Pike GB(4), Richer L(5),
Séguin JR(6), Veillette S(3), Evans CJ(7), Artiges E(8), Banaschewski T(9), Bokde
AW(10), Bromberg U(11), Bruehl R(12), Buchel C(11), Cattrell A(13), Conrod
PJ(14), Flor H(15), Frouin V(16), Gallinat J(11), Garavan H(17), Gowland P(18),
Heinz A(19), Lemaitre H(8), Martinot JL(8), Nees F(15), Orfanos DP(16),
Pangelinan MM(1), Poustka L(9), Rietschel M(15), Smolka MN(20), Walter H(19),
Whelan R(21), Timpson NJ(22), Schumann G(13), Smith GD(22), Pausova Z(23), Paus
T(24).
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.
Comment in
JAMA Psychiatry. 2015 Oct;72(10):969-70.
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 (