Journal article
Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia
Schizophrenia research, Vol.128(1), pp.66-75
2011
DOI: 10.1016/j.schres.2011.02.021
PMCID: PMC3085576
PMID: 21420833
Abstract
Marijuana exposure during the critical period of adolescent brain maturation may disrupt neuro-modulatory influences of endocannabinoids and increase schizophrenia susceptibility. Cannabinoid receptor 1 (CB1/
CNR1) is the principal brain receptor mediating marijuana effects. No study to-date has systematically investigated the impact of
CNR1 on quantitative phenotypic features in schizophrenia and inter-relationships with marijuana misuse. We genotyped 235 schizophrenia patients using 12 tag single nucleotide polymorphisms (tSNPs) that account for most of CB1 coding region genetic variability. Patients underwent a high-resolution anatomic brain magnetic resonance scan and cognitive assessment. Almost a quarter of the sample met DSM marijuana abuse (14%) or dependence (8%) criteria. Effects of
CNR1 tSNPs and marijuana abuse/dependence on brain volumes and neurocognition were assessed using ANCOVA, including co-morbid alcohol/non-marijuana illicit drug misuse as covariates. Significant main effects of
CNR1 tSNPs (rs7766029, rs12720071, and rs9450898) were found in white matter (WM) volumes. Patients with marijuana abuse/dependence had smaller fronto-temporal WM volumes than patients without heavy marijuana use. More interestingly, there were significant rs12720071 genotype-by-marijuana use interaction effects on WM volumes and neurocognitive impairment; suggestive of gene–environment interactions for conferring phenotypic abnormalities in schizophrenia. In this comprehensive evaluation of genetic variants distributed across the CB1 locus,
CNR1 genetic polymorphisms were associated with WM brain volume variation among schizophrenia patients. Our findings suggest that heavy cannabis use in the context of specific
CNR1 genotypes may contribute to greater WM volume deficits and cognitive impairment, which could in turn increase schizophrenia risk.
Details
- Title: Subtitle
- Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia
- Creators
- Beng-Choon HoThomas H WassinkSteven ZiebellNancy C Andreasen
- Resource Type
- Journal article
- Publication Details
- Schizophrenia research, Vol.128(1), pp.66-75
- DOI
- 10.1016/j.schres.2011.02.021
- PMID
- 21420833
- PMCID
- PMC3085576
- NLM abbreviation
- Schizophr Res
- ISSN
- 0920-9964
- eISSN
- 1573-2509
- Publisher
- Elsevier B.V
- Grant note
- MH68380; MH31593; MH40856; MH80128; MH43271 / NIMH Ortho-McNeil Janssen Scientific Affairs
- Language
- English
- Date published
- 2011
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984003907402771
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