Match!

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

Published on Oct 1, 2015in JAMA Psychiatry15.916
· DOI :10.1001/jamapsychiatry.2015.1131
Leon French14
Estimated H-index: 14
,
Courtney Gray1
Estimated H-index: 1
+ 35 AuthorsTomáš Paus86
Estimated H-index: 86
Sources
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.
Figures & Tables
  • References (60)
  • Citations (70)
📖 Papers frequently viewed together
201443.07Nature
300 Authors (Stephan Ripke, ..., Michael O. Donovan)
3,480 Citations
200227.60BMJ
949 Citations
1,016 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References60
Newest
#1M. Pesaresi (U of T: University of Toronto)H-Index: 2
#2R. Soon-Shiong (U of T: University of Toronto)H-Index: 1
Last. Tomáš Paus (U of T: University of Toronto)H-Index: 86
view all 6 authors...
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...
27 CitationsSource
#1Amanda Borgquist (Western University of Health Sciences)H-Index: 6
#2Cecilia Meza (Western University of Health Sciences)H-Index: 5
Last. Edward J. Wagner (Western University of Health Sciences)H-Index: 17
view all 3 authors...
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...
17 CitationsSource
#1Matchen S Keshavan (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 97
#2Jay N. Giedd (NIH: National Institutes of Health)H-Index: 103
Last. Tomáš Paus (U of T: University of Toronto)H-Index: 86
view all 5 authors...
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...
80 CitationsSource
#1Tomáš Paus (U of T: University of Toronto)H-Index: 86
#2M. Pesaresi (U of T: University of Toronto)H-Index: 2
Last. Leon French (U of T: University of Toronto)H-Index: 14
view all 3 authors...
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...
33 CitationsSource
#1Stephan Ripke (Broad Institute)H-Index: 74
#2Benjamin M. Neale (Broad Institute)H-Index: 85
Last. Michael O. Donovan (Cardiff University)H-Index: 122
view all 300 authors...
3,480 CitationsSource
#1Albert Batalla (University of Barcelona)H-Index: 12
#2Carles Soriano-Mas (Bellvitge University Hospital)H-Index: 30
Last. Rocío Martín-SantosH-Index: 41
view all 14 authors...
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...
23 CitationsSource
#1Yves Henchoz (UNIL: University of Lausanne)H-Index: 12
#2Marc Dupuis (UNIL: University of Lausanne)H-Index: 8
Last. Gerhard GmelH-Index: 62
view all 8 authors...
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...
15 CitationsSource
#1Jean-Luc LemahieuH-Index: 1
#2Angela MeH-Index: 1
115 CitationsSource
#1Sheeja Navakkode (Braunschweig University of Technology)H-Index: 12
#2Martin Korte (Braunschweig University of Technology)H-Index: 41
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 ...
14 CitationsSource
#1P. C. M. P. Koolschijn (LEI: Leiden University)H-Index: 2
#2Jiska S. Peper (LEI: Leiden University)H-Index: 30
Last. Eveline A. Crone (LEI: Leiden University)H-Index: 53
view all 3 authors...
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...
44 CitationsSource
Cited By70
Newest
#1Jacqueline-Marie N. Ferland (ISMMS: Icahn School of Medicine at Mount Sinai)
#2Yasmin L. Hurd (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 61
There have been dramatic changes worldwide in the attitudes toward and consumption of recreational and medical cannabis. Cannabinoid receptors, which mediate the actions of cannabis, are abundantly expressed in brain regions known to mediate neural processes underlying reward, cognition, emotional regulation and stress responsivity relevant to addiction vulnerability. Despite debates regarding potential pathological consequences of cannabis use, cannabis use disorder is a clinical diagnosis with...
Source
Last. Nicholas G. MartinH-Index: 157
view all 12 authors...
Abstract It is well established that higher cognitive ability is associated with larger brain size. However, individual variation in intelligence exists despite brain size and recent studies have shown that a simple unifactorial view of the neurobiology underpinning cognitive ability is probably unrealistic. Educational attainment (EA) is often used as a proxy for cognitive ability since it is easily measured, resulting in large sample sizes and, consequently, sufficient statistical power to det...
Source
#1Sergi Mas (University of Barcelona)H-Index: 18
#2Daniel Boloc (University of Barcelona)H-Index: 4
Last. Ana González-PintoH-Index: 44
view all 18 authors...
Gene-environment (GxE) interactions have been related to psychosis spectrum disorders, involving multiple common genetic variants in multiple genes with very small effect sizes, and several environmental factors that constitute a dense network of exposures named the exposome. Here, we aimed to analyze GxE in a cohort of 310 first-episode psychotic (FEP) and 236 healthy controls, by using aggregate scores estimated in large populations such as the polygenic risk score for schizophrenia and (PRS-S...
Source
#1Grace R Jacobs (CAMH: Centre for Addiction and Mental Health)H-Index: 1
#2Aristotle N. Voineskos (CAMH: Centre for Addiction and Mental Health)H-Index: 33
Schizophrenia is a highly heritable disorder characterized by disruptions on the molecular, cellular, and neural circuit level that lead to the behaviors and cognitive impairments associated with the illness. This chapter evaluates how combining neuroimaging methods with genetic approaches such as studying single genes and polygenic risk scores, to genome-wide association study (GWAS) variants and gene expression networks, can provide valuable insight into both biomarkers of schizophrenia and un...
Source
#1Joseph M. Boden (University of Otago)H-Index: 41
#2Bhubaneswor Dhakal (University of Otago)H-Index: 3
Last. L. J. Horwood (University of Otago)H-Index: 98
view all 4 authors...
Source
#1Elham AssaryH-Index: 4
#2John Paul VincentH-Index: 1
Last. Michael PluessH-Index: 24
view all 5 authors...
Source
#2Rose Chesworth (USYD: University of Sydney)H-Index: 11
view all 2 authors...
Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasi...
Source
#1Lucia Sideli ('KCL': King's College London)H-Index: 9
#2Harriet Quigley ('KCL': King's College London)H-Index: 2
Last. Robin M. Murrayand ('KCL': King's College London)H-Index: 149
view all 4 authors...
AbstractObjective: This review discusses the relationship between cannabis use and psychotic, bipolar, depressive, and anxiety disorders, as well as suicide. It summarizes epidemiological evidence ...
4 CitationsSource
There is a need to identify biomarkers which could indicate the occurrence of brain injury in drug abuse. We aimed to investigate ubiquitin-C-terminal hydrolase-1 (UCH-L1), a neuronal cell body injury marker, the glial protein S-100 beta (S100β), and the glial fibrillary acidic protein (GFAP) as putative markers for neuronal injury due to cannabis, tramadol, or their combined use. Rats were treated with cannabis and/or tramadol subcutaneously daily for 6 weeks and UCH-L1, S100β, and GFAP were im...
Source
#1Martijn P. van den Heuvel (VU: VU University Amsterdam)H-Index: 8
#2Lianne H. Scholtens (VU: VU University Amsterdam)H-Index: 12
Last. René S. Kahn (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 108
view all 3 authors...
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...
1 CitationsSource