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The influence of cannabis use on schizophrenia susceptibility, a gene-environment interaction study in adolescent.

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Titel: Cannabis Use as an Indicator of Risk for Mental Health Problems in Adolescents: a population-based study at secondary schools.
Auteur: van Gastel WA,Tempelaar W, Bun C, Schubart CD, Kahn RS, Plevier C , Boks MPM.
Magazine: Psychological Medicine
Titel: Family-Based Analysis of Genetic Variation Underlying Psychosis-Inducing Effects of Cannabis: Sibling Analysis and Proband Follow-up.
Auteur: van Winkel R; Genetic Risk and Outcome of Psychosis (GROUP) Investigators.
Titel: Investigating gene environment interaction in complex diseases
Auteur: Boks MP, Schipper M, Schubart CD, Sommer IE, Kahn RS, Ophoff RA.
Magazine: International Journal of Epidemiology
Titel: Perceived School Safety is Strongly Associated with Mental Health Problem in Adolescents
Auteur: Nijs MM, Bun CJE, Tempelaar WM, de Wit NJ, Burger H, Plevier CM, Boks MP.
Magazine: Community Mental Health Journal
Titel: Evidence That Familial Liability for Psychosis Is Expressed as Differential Sensitivity to Cannabis: An Analysis of Patient-Sibling and Sibling-Control Pairs.
Auteur: Genetic Risk and Outcome in Psychosis (GROUP) Investigators
Titel: Association between cannabis and psychiatric hospitalization.
Auteur: Schubart CD, Boks MP, Breetvelt EJ, van Gastel WA, Groenwold RH, Ophoff RA, Sommer IE, Kahn RS.
Magazine: Acta Psychiatrica Scandinavica
Titel: Advanced paternal age and vulnerability to psychotic-like experiences in the offspring.
Auteur: Vreeker A, Schubart CD, van Gastel WA, Kahn RS, Boks MP. Schizophr Res.
Magazine: Schizophrenia Research
Titel: Cannabis use at a young age is associated with psychotic experiences.
Auteur: Schubart CD, van Gastel WA, Breetvelt EJ, Beetz SL, Ophoff RA, Sommer IE, Kahn RS, Boks MP.
Magazine: Psychological Medicine
Titel: Cigarette smoking is equally strongly associated with Psychotic-Like experiences as Cannabis Use: a cross-sectional study in young Adults.
Auteur: van Gastel WA, MacCabe JH, Schubart CD, Vreeker A, Tempelaar W, Kahn RS, Boks MPM
Magazine: Psychological Medicine
Titel: Cannabis with high cannabidiol content is associated with fewer psychotic experiences.
Auteur: Schubart CD, Sommer IE, van Gastel WA, Goetgebuer RL, Kahn RS, Boks MP.
Magazine: Schizophrenia Research
Titel: Cannabis use and subclinical positive psychotic experiences in early adolescence
Auteur: van Gastel WA, Wigman JT, Monshouwer K, Kahn RS, van Os J, Boks MP, Vollebergh WA.
Magazine: Addiction
Titel: A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.
Auteur: de Jong S, Boks MP, Fuller TF, Strengman E, Janson E, de Kovel CG, Ori AP, Vi N,Mulder F, Blom JD, Glenthøj B, Schubart CD, Cahn W, Kahn RS, Horvath S, Ophoff RA.
Magazine: PlosOne
Titel: Cannabis Beyond Good and Evil
Auteur: C.D. Schubart
Titel: Cannabis use and mental health.
Auteur: van Gastel W. (Geneeskunde), Promotor Prof Dr RS Kahn, Co-promotor: dr MP Boks,

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Eindverslag

In deze studie werd onderzocht welke genetisch en epidemiologische risicofactoren bepalen of personen gevoelig zijn voor de effecten van cannabis op psychiatrische symptomen. Het blijkt dat met name cannabis gebruik op jongere leeftijd (en in het bijzonder voor het 15e jaar) alsook zwaar cannabis gebruik (in het bijzonder vaker dan wekelijks en soorten met een hoge THC concentratie) samen gaan met meer psychiatrische problemen en opnames, en in het bijzonder met meer psychotische ervaringen. Matig cannabis gebruik is vooral een indicatie dat er ook veel andere risicofactoren voor psychiatrische problemen aanwezig zijn. De genen die betrokken zijn in de effecten van cannabis hebben met name een functie in de uitgroei van zenuwcellen en staan in relatie met de natuurlijk cannabis achtige stoffen in ons brein (cannabinoiden). De vondst van deze genen ondersteunen de hypothese dat immuun cellen in ons brein (microglia) een rol spelen bij de gevoeligheid van psychose.

Samenvatting van de aanvraag

- SAMENVATTING/ SUMMARY Compelling evidence suggests that cannabis use substantially increases the vulnerability to develop schizophrenia and that genetic factors moderate this influence. With an odds ratio estimated at 2.09 and a prevalence of cannabis use in adolescents of around 9 percent it is apparent that cannabis use poses a serious risk for developing schizophrenia. However, the molecular mechanism by which cannabis increases the risk to schizophrenia and the role genetic factors herein is still largely unknown. We have collected information on drug use and subclinical symptoms of psychosis by means of the Community Assessment of Psychic Experiences (CAPE) in a sample of 12.000 adolescents. Preliminary analyses confirm that cannabis use is associated with higher levels of psychosis. Further study of the interaction between genes and cannabis exposure is essential to identify the genetic factors that underlie the effects of cannabis in the aetiology of schizophrenia. This study aims to identify genetic variation that underlies the interaction between genes, cannabis use and the risk to develop schizophrenia. We propose a two-stage genome wide association study in highly selected subjects to overcome the methodological difficulties that are associated with studies of gene-environment interaction. Population-based selective sampling of heavy- and non users of cannabis, and those with many symptoms and no symptoms, leads to substantially reduction of required sample size while maintaining statistical power. In the first stage DNA of a highly selected group (N=520) will be subject to a whole genome screen, in stage two selected SNPs from stage one will be genotyped in an additional sample (N=880). Identification of the genetic factors that regulate the influence of cannabis use on the devopment of schizophrenia will lead to a better understanding of the effects of cannabis on the brain as well as contribute to the understanding of the aetiology of schizophrenia. It will provide the starting point of further molecular studies with the ultimate goal of early detection, prevention and treatment of schizophrenia.

Onderwerpen

Kenmerken

Projectnummer:
91207039
Looptijd: 100%
Looptijd: 100 %
2008
2012
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. R.S. Kahn
Verantwoordelijke organisatie:
Universitair Medisch Centrum Utrecht