MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse

O E Onwuameze; K W Nam; E A Epping; T H Wassink; S Ziebell; N C Andreasen; B-C Ho

doi:10.1017/S0033291712001559

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MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse

Journal article

Peer reviewed

MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse

O E Onwuameze, K W Nam, E A Epping, T H Wassink, S Ziebell, N C Andreasen and B-C Ho

Psychological medicine, Vol.43(3), pp.619-631

03/2013

DOI: 10.1017/S0033291712001559

PMCID: PMC3847818

PMID: 22850347

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https://www.ncbi.nlm.nih.gov/pmc/articles/3847818View

Open Access

Abstract

Adolescent marijuana use is associated with increased risk for schizophrenia. We previously reported that marijuana misuse in conjunction with specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia patients. In this study, we assessed the influence of another cannabinoid-related gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14-CNR1 gene-gene interactions in conferring brain volume abnormalities among schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member of the MAPK family involved in diverse cellular processes, including CNR1-induced apoptosis. We genotyped 235 schizophrenia patients on nine MAPK14 tag single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain volumes across patients with versus without marijuana abuse/dependence were examined using ANCOVA. Of the MAPK14 tSNPs, only rs12199654 had significant genotype effects and genotype × marijuana misuse interaction effects on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14 rs12199654 on WM volume deficits remained significant even after controlling for the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14 CNR1 diplotype and diplotype × marijuana interaction on WM brain volumes, with both genetic variants having additive contributions to WM volume deficits only in patients with marijuana misuse. Given that CNR1-induced apoptosis is preceded by increased MAPK phosphorylation, our study suggests that potential MAPK14-CNR1 gene-gene interactions may mediate brain morphometric features in schizophrenia patients with heavy marijuana use.

Humans

Magnetic Resonance Imaging - methods

Male

Schizophrenia - pathology

Young Adult

Schizophrenia - genetics

Adult

Female

Marijuana Abuse - genetics

Genetic Predisposition to Disease

Linkage Disequilibrium - genetics

Marijuana Abuse - pathology

Organ Size

Rats

Genotype

Epistasis, Genetic - genetics

Mitogen-Activated Protein Kinase 14 - genetics

Animals

Receptor, Cannabinoid, CB1 - genetics

Analysis of Variance

Image Processing, Computer-Assisted

Adolescent

Alleles

Brain - pathology

Polymorphism, Single Nucleotide - genetics

Apoptosis

Diagnosis, Dual (Psychiatry)

Details

Title: Subtitle: MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse
Creators: O E Onwuameze - Department of Psychiatry, Southern Illinois University Medical School, Springfield, IL, USA
K W Nam
E A Epping
T H Wassink
S Ziebell
N C Andreasen
B-C Ho
Resource Type: Journal article
Publication Details: Psychological medicine, Vol.43(3), pp.619-631
DOI: 10.1017/S0033291712001559
PMID: 22850347
PMCID: PMC3847818
NLM abbreviation: Psychol Med
ISSN: 0033-2917
eISSN: 1469-8978
Publisher: England
Grant note: R01 MH097751 / NIMH NIH HHS MH68380 / NIMH NIH HHS R01 MH080128 / NIMH NIH HHS MH31593 / NIMH NIH HHS MH40856 / NIMH NIH HHS R01 MH031593 / NIMH NIH HHS R01 MH060990 / NIMH NIH HHS R01 MH040856 / NIMH NIH HHS R37 MH031593 / NIMH NIH HHS MH43271 / NIMH NIH HHS K23 MH068380 / NIMH NIH HHS MH80128 / NIMH NIH HHS
Language: English
Date published: 03/2013
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
Record Identifier: 9984003428102771

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