AUTHOR=Bustillo Juan R. , Patel Veena , Jones Thomas , Jung Rex , Payaknait Nattida , Qualls Clifford , Canive Jose M. , Liu Jingyu , Perrone-Bizzozero Nora Irma , Calhoun Vince D. , Turner Jessica A. , Gasparovic Charles 

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

JOURNAL=Frontiers in Psychiatry

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2017.00079

DOI=10.3389/fpsyt.2017.00079

ISSN=1664-0640

ABSTRACT=<sec id="ST1"><title>Background</title><p>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 polymorphisms and brain Glx levels in schizophrenia.</p></sec><sec id="ST2"><title>Methods</title><p><sup>1</sup>H-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 <italic>CLCN3</italic>, rs12704290 in GRM3, and rs12325245 in <italic>SLC38A7</italic>), and three calcium signaling polymorphisms (rs1339227 in <italic>RIMS1</italic>, rs7893279 in <italic>CACNB2</italic>, and rs2007044 in <italic>CACNA1C</italic>). Summary risk scores for the three glutamate and the three calcium polymorphisms were calculated.</p></sec><sec id="ST3"><title>Results</title><p>Glx levels in GM positively correlated with glutamate-related genetic risk score but only in younger (≤36 years) schizophrenia patients (<italic>p</italic> = 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 (<italic>p</italic> &lt; 0.001).</p></sec><sec id="ST4"><title>Conclusion</title><p>Elevations in brain Glx are in part, related to common allelic variants of glutamate-related genes known to increase the risk for schizophrenia. Since the glutamate risk scores did not differ between groups, some other genetic or environmental factors likely interact with the variability in glutamate-related risk SNPs to contribute to an increase in brain Glx early in the illness.</p></sec>