Dataset Information

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia.

ABSTRACT: BACKGROUND:The proton magnetic resonance spectroscopy (1H-MRS) signals from glutamate (or the combined glutamate and glutamine signal-Glx) have been found to be greater in various brain regions in people with schizophrenia. Recently, the Psychiatric Genetics Consortium reported that several common single-nucleotide polymorphisms (SNPs) in glutamate-related genes confer increased risk of schizophrenia. Here, we examined the relationship between presence of these risk polymorphisms and brain Glx levels in schizophrenia. METHODS:1H-MRS imaging data from an axial, supraventricular tissue slab were acquired in 56 schizophrenia patients and 67 healthy subjects. Glx was measured in gray matter (GM) and white matter (WM) regions. The genetic data included six polymorphisms genotyped across an Illumina 5M SNP array. Only three of six glutamate as well as calcium-related SNPs were available for examination. These included three glutamate-related polymorphisms (rs10520163 in CLCN3, rs12704290 in GRM3, and rs12325245 in SLC38A7), and three calcium signaling polymorphisms (rs1339227 in RIMS1, rs7893279 in CACNB2, and rs2007044 in CACNA1C). Summary risk scores for the three glutamate and the three calcium polymorphisms were calculated. RESULTS:Glx levels in GM positively correlated with glutamate-related genetic risk score but only in younger (?36?years) schizophrenia patients (p?=?0.01). Glx levels did not correlate with calcium risk scores. Glx was higher in the schizophrenia group compared to levels in controls in GM and WM regardless of age (p?

SUBMITTER: Bustillo JR

PROVIDER: S-EPMC5466972 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia.

Bustillo Juan R JR Patel Veena V Jones Thomas T Jung Rex R Payaknait Nattida N Qualls Clifford C Canive Jose M JM Liu Jingyu J Perrone-Bizzozero Nora Irma NI Calhoun Vince D VD Turner Jessica A JA Gasparovic Charles C

Frontiers in psychiatry 20170612

<h4>Background</h4>The proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) signals from glutamate (or the combined glutamate and glutamine signal-Glx) have been found to be greater in various brain regions in people with schizophrenia. Recently, the Psychiatric Genetics Consortium reported that several common single-nucleotide polymorphisms (SNPs) in glutamate-related genes confer increased risk of schizophrenia. Here, we examined the relationship between presence of these risk polymorphi ...[more]

PMID: 28659829

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Project description:Proton magnetic resonance spectroscopy (1H-MRS) studies have examined glutamatergic abnormalities in schizophrenia and bipolar-I disorders, mostly in single voxels. Though the critical nodes remain unknown, schizophrenia and bipolar-I involve brain networks with broad abnormalities. To provide insight on the biochemical differences that may underlie these networks, the combined glutamine and glutamate signal (Glx) and other metabolites were examined in patients in early psychosis with whole brain 1H-MRS imaging (1H-MRSI). Data were acquired in young schizophrenia subjects (N = 48), bipolar-I subjects (N = 21) and healthy controls (N = 51). Group contrasts for Glx, as well as for N-acetyl aspartate, choline, myo-inositol and creatine, from all voxels that met spectral quality criteria were analyzed in standardized brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05) analysis. Schizophrenia subjects had higher Glx in the right middle cingulate gyrus (19 voxels, CCLAV = 0.05) than bipolar-I subjects. Healthy controls had intermediate Glx values, though not significant. Schizophrenia subjects also had higher N-acetyl aspartate (three clusters, left occipital, left frontal, right frontal), choline (two clusters, left and right frontal) and myo-inositol (one cluster, left frontal) than bipolar-I, with healthy controls having intermediate values. These increases were likely accounted for by antipsychotic medication effects in the schizophrenia subgroup for N-acetyl aspartate and choline. Likewise, creatine was increased in two clusters in treated vs. antipsychotic-naïve schizophrenia, supporting a medication effect. Conversely, the increments in Glx in right cingulate were not driven by antipsychotic medication exposure. We conclude that increments in Glx in the cingulate may be critical to the pathophysiology of schizophrenia and are consistent with the NMDA hypo-function model. This model however may be more specific to schizophrenia than to psychosis in general. Postmortem and neuromodulation schizophrenia studies focusing on right cingulate, may provide critical mechanistic and therapeutic advancements, respectively.

Dataset Information

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia.

Publications

Risk-Conferring Glutamatergic Genes and Brain Glutamate Plus Glutamine in Schizophrenia.

Similar Datasets

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