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

Published on Oct 1, 2015in JAMA Psychiatry15.92
· DOI :10.1001/jamapsychiatry.2015.1131
Leon French14
Estimated H-index: 14
,
Courtney Gray1
Estimated H-index: 1
+ 35 AuthorsTomáš Paus82
Estimated H-index: 82
Cite
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-a-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-a-vis a change in decreasing cortical thickness from 14.5 to 18.5 years of age ( t 137  = −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 ( 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.
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  • References (60)
  • Citations (63)
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References60
Newest
Published on Jul 1, 2015in NeuroImage5.81
M. Pesaresi2
Estimated H-index: 2
(U of T: University of Toronto),
R. Soon-Shiong1
Estimated H-index: 1
(U of T: University of Toronto)
+ 3 AuthorsTomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto)
Abstract Testosterone is a sex hormone involved in brain maturation via multiple molecular mechanisms. Previous human studies described age-related changes in the overall volume and structural properties of white matter during male puberty. Based on this work, we have proposed that testosterone may induce a radial growth of the axon and, possibly, modulate axonal transport. In order to determine whether this is the case we have used two different experimental approaches. With electron microscopy...
Amanda Borgquist6
Estimated H-index: 6
(Western University of Health Sciences),
Cecilia Meza5
Estimated H-index: 5
(Western University of Health Sciences),
Edward J. Wagner17
Estimated H-index: 17
(Western University of Health Sciences)
Orexigenic mediators can impact the hypothalamic feeding circuitry via the activation of AMP-dependent protein kinase (AMPK). Given that testosterone is an orexigenic hormone, we hypothesized that androgenic changes in energy balance are due to enhanced cannabinoid-induced inhibition of anorexigenic proopiomelanocortin (POMC) neurons via activation of AMPK. To this end, whole animal experiments were carried out in gonadectomized male guinea pigs treated subcutaneously with either testosterone pr...
Published on Dec 1, 2014in The Lancet Psychiatry18.33
Matchen S Keshavan94
Estimated H-index: 94
(BIDMC: Beth Israel Deaconess Medical Center),
Jay N. Giedd97
Estimated H-index: 97
(NIH: National Institutes of Health)
+ 2 AuthorsTomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto)
Summary Adolescence is a time of extensive neuroanatomical, functional, and chemical reorganisation of the brain which parallels substantial maturational changes in cognition and affect regulation. This period is characterised by stabilisation of synapses to diminish redundancy and increase efficiency of neural function, fine-tuning of excitatory and inhibitory neurotransmitter systems, beginning of integration between late maturing and early maturing brain structures, and development of effecti...
Published on Sep 1, 2014in Neuroscience3.24
Tomáš Paus82
Estimated H-index: 82
(U of T: University of Toronto),
M. Pesaresi2
Estimated H-index: 2
(U of T: University of Toronto),
Leon French14
Estimated H-index: 14
(U of T: University of Toronto)
Abstract There are two ways to picture white matter: as a grid of electrical wires or a network of roads. The first metaphor captures the classical function of an axon as conductor of action potentials (and information) from one brain region to another. The second one points to the important role of axons in a bi-directional transport of biological molecules and organelles between the cell body and synapse. Given the wide variety of such cargoes, a well-functioning axonal transport is critical f...
Published on Jul 1, 2014in Addiction Biology4.22
Albert Batalla11
Estimated H-index: 11
(University of Barcelona),
Carles Soriano-Mas24
Estimated H-index: 24
(Bellvitge University Hospital)
+ 11 AuthorsSantiago Nogué-Xarau21
Estimated H-index: 21
(University of Barcelona)
Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior...
Published on Jul 1, 2014in Preventive Medicine3.45
Yves Henchoz12
Estimated H-index: 12
(UNIL: University of Lausanne),
Marc Dupuis8
Estimated H-index: 8
(UNIL: University of Lausanne)
+ 5 AuthorsGerhard Gmel60
Estimated H-index: 60
Abstract Objective This study aims to measure the associations of physical activity and one of its components, sport and exercise, with at-risk substance use in a population of young men. Method Baseline (2010–2012) and follow-up (2012–2013) data of 4748 young Swiss men from the Cohort Study on Substance Use Risk Factors (C-SURF) were used. Cross-sectional and prospective associations between at-risk substance use and both sport and exercise and physical activities were measured using Chi-square...
Published on Jun 1, 2014
Jean-Luc Lemahieu1
Estimated H-index: 1
,
Angela Me1
Estimated H-index: 1
Published on Apr 1, 2014in Neuropharmacology4.37
Sheeja Navakkode12
Estimated H-index: 12
(Braunschweig University of Technology),
Martin Korte39
Estimated H-index: 39
(Braunschweig University of Technology)
Abstract Cognitive impairment is one of the most important side effects associated with cannabis drug abuse, as well as the serious issue concerning the therapeutic use of cannabinoids. Cognitive impairments and neuropsychiatric symptoms are caused by early synaptic dysfunctions, such as loss of synaptic connections in different brain structures including the hippocampus, a region that is believed to play an important role in certain forms of learning and memory. We report here that metaplastic ...
Published on Jan 8, 2014in PLOS ONE2.78
P. Cédric M. P. Koolschijn19
Estimated H-index: 19
(LEI: Leiden University),
Jiska S. Peper29
Estimated H-index: 29
(LEI: Leiden University),
Eveline A. Crone50
Estimated H-index: 50
(LEI: Leiden University)
Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8–25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with lut...
Published on Jan 3, 2014in Annual Review of Psychology19.75
Sarah-Jayne Blakemore S-J64
Estimated H-index: 64
(UCL: University College London),
Kathryn L. Mills16
Estimated H-index: 16
(NIH: National Institutes of Health)
Adolescence is a period of formative biological and social transition. Social cognitive processes involved in navigating increasingly complex and intimate relationships continue to develop throughout adolescence. Here, we describe the functional and structural changes occurring in the brain during this period of life and how they relate to navigating the social environment. Areas of the social brain undergo both structural changes and functional reorganization during the second decade of life, p...
Cited By63
Newest
Published on May 1, 2019in Biological Psychiatry11.50
Martijn P Van den Heuvel (VU: VU University Amsterdam), Lianne H. Scholtens11
Estimated H-index: 11
(VU: VU University Amsterdam),
R.S. Kahn94
Estimated H-index: 94
(ISMMS: Icahn School of Medicine at Mount Sinai)
Abstract The human brain comprises a multiscale network with multiple levels of organization. Neurons with dendritic and axonal connections form the microscale fabric of brain circuitry, and macroscale brain regions and white matter connections form the infrastructure for system-level brain communication and information integration. In this review, we discuss the emerging trend of multiscale neuroscience, the multidisciplinary field that brings together data from these different levels of nervou...
Published on Apr 1, 2019in Biological Psychiatry11.50
Emma Neilson4
Estimated H-index: 4
(Royal Edinburgh Hospital),
Xueyi Shen6
Estimated H-index: 6
(Royal Edinburgh Hospital)
+ 11 AuthorsGail Davies46
Estimated H-index: 46
(Edin.: University of Edinburgh)
Abstract Background Schizophrenia is a neurodevelopmental disorder with many genetic variants of individually small effect contributing to phenotypic variation. Lower cortical thickness (CT), surface area, and cortical volume have been demonstrated in people with schizophrenia. Furthermore, a range of obstetric complications (e.g., lower birth weight) are consistently associated with an increased risk for schizophrenia. We investigated whether a high polygenic risk score for schizophrenia (PGRS-...
Published on Sep 11, 2019in Molecular Psychiatry11.97
Suheyla Cetin-Karayumak (Brigham and Women's Hospital), Maria A. Di Biase6
Estimated H-index: 6
(Brigham and Women's Hospital)
+ 28 AuthorsMark G. Vangel48
Estimated H-index: 48
(Harvard University)
Several prominent theories of schizophrenia suggest that structural white matter pathologies may follow a developmental, maturational, and/or degenerative process. However, a lack of lifespan studies has precluded verification of these theories. Here, we analyze the largest sample of carefully harmonized diffusion MRI data to comprehensively characterize age-related white matter trajectories, as measured by fractional anisotropy (FA), across the course of schizophrenia. Our analysis comprises di...
Published on Nov 22, 2018in Schizophrenia Bulletin7.29
Tao Tan9
Estimated H-index: 9
(UB: University at Buffalo),
Wei Wang5
Estimated H-index: 5
(UB: University at Buffalo)
+ 3 AuthorsZhen Yan54
Estimated H-index: 54
(UB: University at Buffalo)
Published on 2019in Neuropsychopharmacology7.16
J. Cobb Scott19
Estimated H-index: 19
(UPenn: University of Pennsylvania),
Adon F.G. Rosen4
Estimated H-index: 4
(UPenn: University of Pennsylvania)
+ 6 AuthorsRuben C. Gur111
Estimated H-index: 111
(UPenn: University of Pennsylvania)
Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, high-resolution T1-weighted MRIs were obtained from 781 youth aged 14–22 years who were studied as part of the Philadelphia Neurodevelopmental Cohort. Th...
Tao Yu5
Estimated H-index: 5
,
Tianye Jia14
Estimated H-index: 14
(Fudan University)
+ 38 AuthorsBernd Ittermann22
Estimated H-index: 22
(German National Metrology Institute)
Abstract Objective Cannabis consumption during adolescence has been reported as a risk-factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still ill-described. Method 706 adolescents from the general population that were recruited by the IMAGEN consortium had structural MRI scans both at 14 and 19 years-old. We used deformation-based morphometry to map voxel-wise brain changes between the two time points...
Published on Mar 19, 2019in European Journal of Pain3.19
Marie-Odile Krebs2
Estimated H-index: 2
(Paris V: Paris Descartes University),
Oussama Kébir1
Estimated H-index: 1
(Paris V: Paris Descartes University),
Therese M. Jay (Paris V: Paris Descartes University)
Published on Mar 7, 2019in Schizophrenia Bulletin7.29
Thomas Lancaster9
Estimated H-index: 9
(Cardiff University),
Stavros L Dimitriadis1
Estimated H-index: 1
(Cardiff University)
+ 12 AuthorsGeorge Davey-Smith177
Estimated H-index: 177
(UoB: University of Bristol)
Risk profile scores (RPS) derived from genome-wide association studies (GWAS) explain a considerable amount of susceptibility for schizophrenia (SCZ). However, little is known about how common genetic risk factors for SCZ influence the structure and function of the human brain, largely due to the constraints of imaging sample sizes. In the current study, we use a novel recall-by-genotype (RbG) methodological approach, where we sample young adults from a population cohort (Avon Longitudinal Study...
View next paperModeration of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction.