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Association of GRM3 polymorphism with white matter integrity in schizophrenia.

ABSTRACT: While the functional disconnectivity hypothesis of schizophrenia has received considerable attention, fewer studies have investigated the contribution of genotype to structural connectivity between brain regions either in schizophrenia patients or in healthy controls. In this study, we obtained diffusion tensor imaging (DTI) data and genome-wide single nucleotide polymorphism (SNP) data from 74 cases and 87 age- and gender-matched controls.We used independent component analysis (ICA) to analyze fractional anisotropy (FA) values and correlated FA values with 121 SNPs in genes associated with myelination and/or schizophrenia risk.Using ICA, we identified 6 maximally independent components in which the majority of the voxels corresponded to known white matter (WM) tracts. Among these WM-enriched components, two had FA values that were significantly decreased in patients. In addition, we examined the relationship between FA values and genotype and found that a SNP located in the intronic region of the metabotropic glutamate receptor 3 gene, GRM3, shows a significant correlation with FA values in a component containing tracts from the cortico-cerebellar-thalamic-cortical circuit of patients but not controls.Our findings strengthen the evidence for an association between GRM3 genotype and schizophrenia and suggest a role for glutamate neurotransmission in the establishment and maintenance of myelinated fibers.

SUBMITTER: Mounce J

PROVIDER: S-EPMC4022143 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Association of GRM3 polymorphism with white matter integrity in schizophrenia.

Mounce Joanna J Luo Li L Caprihan Arvind A Liu Jingyu J Perrone-Bizzozero Nora I NI Calhoun Vince D VD

Schizophrenia research 20140326 1-3

<h4>Background</h4>While the functional disconnectivity hypothesis of schizophrenia has received considerable attention, fewer studies have investigated the contribution of genotype to structural connectivity between brain regions either in schizophrenia patients or in healthy controls. In this study, we obtained diffusion tensor imaging (DTI) data and genome-wide single nucleotide polymorphism (SNP) data from 74 cases and 87 age- and gender-matched controls.<h4>Methods</h4>We used independent c ...[more]

PMID: 24680030

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Project description:Background: Schizophrenia is characterized by the disruption of microstructural white matter (WM) integrity, while the pathogenesis remains unclear. Inflammation has been associated with the WM pathology in schizophrenia. Interleukin 10 (IL-10) has been proven to be related to schizophrenia in both animal and human models. The aim of this study was to explore whether peripheral IL-10 was associated with microstructural WM integrity in schizophrenia. Methods: A total of 47 patients with schizophrenia (SZ) and 49 healthy controls (HC) underwent diffusion tensor imaging and venous blood sampling. Tract-based spatial statistics was conducted to explore the differences in fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD) between patients and controls. A quantitative chemiluminescence assay was performed to measure peripheral IL-10 levels. General linear regression analysis using a stepwise method was applied to examine the relationship between peripheral IL-10 and diffusion measures. Results: Compared with the HC, peripheral IL-10 levels were higher and a significant reduction of FA and AD, and increase of RD and MD were observed in SZ (corrected p < 0.05). A regression analysis revealed that peripheral IL-10 was negatively correlated with FA in the right posterior thalamic radiation and left inferior fronto-occipital fasciculus, in SZ (β = -0.51, p = 0.01; β = -0.47, p = 0.02, respectively) but not in HC (β = -0.01, p = 0.95; β = -0.003, p = 0.98, respectively), and the differences in regression curves were significant (z = 2.50, p = 0.01; z = 2.37, p = 0.02, respectively). IL-10 was negatively connected with MD in the right parietal arcuate fasciculus (β = -0.40, p = 0.048) and body of the corpus callosum (β = -0.43, p = 0.03) in SZ, while not in HC. The magnitude of correlation in the patient and control group was different (z = 2.48, p = 0.01 and z = 2.61, p < 0.01, respectively). In addition, IL-10 was positively correlated with RD in the right parietal arcuate fasciculus in patients (β = 0.45, p = 0.04) but not in HC (β = 0.26, p = 0.94), but the correlation coefficients were not significant (z = 0.98, p = 0.32). Conclusion: Our findings demonstrated that elevated peripheral IL-10 levels were associated with the disruption of microstructural WM integrity in schizophrenia, supporting the notion that inflammation plays a regulatory role in the pathology of microstructural WM and is associated with schizophrenia.

Dataset Information

Association of GRM3 polymorphism with white matter integrity in schizophrenia.

Publications

Association of GRM3 polymorphism with white matter integrity in schizophrenia.

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