Altered excitatory and inhibitory neurotransmitter and neuromodulator systems are implicated in the pathophysiology of schizophrenia. Over the last few years, there has been particular interest in the role of the glutamatergic system in the development of schizophrenia. MRS studies have reported altered anterior cingulate glutamate (Glu), glutamine (Gln), and GABA in schizophrenia^1,2, but few studies have examined multiple cortical and subcortical regions, and relationship to symptoms. The purpose of this study was to investigate cortico-thalamic neurochemical differences in participants with and without schizophrenia using 7T MRS.Thirty-one participants with schizophrenia (13 males, age: 34±13 years) and 31 psychiatric healthy controls (19 males, age: 28±9years) have completed this study to date. The patients functional, cognitive and symptom status were assessed with the UCSD Performance-Based Skills Assessment (UPSA-2) score, the MATRICS Consensus Cognitive Battery (MCCB) composite scores, and the Brief Psychiatric Rating Scale (BPRS) total scores. All patients except 1 (un-medicated) were all treated with second generation antipsychotic medication; exclusion criteria included no current use of benzodiazepines, mood stabilizers, or anti-cholinergics, and no current substance abuse or dependence. All participants were scanned using a 7T scanner (Philips ‘Achieva’, Best, Netherlands) equipped with a 32-channel head coil (Nova Medical, Orlando, FL). Regions thought to be involved in the pathophysiology of schizophrenia were targeted namely the anterior cingulate (ACC), thalamus (Thal), dorsolateral prefrontal cortex (DPFLC), hippocampus (HP), and centrum semiovale (CSO), were assessed. Voxel sizes were ACC; 30x20x20 mm³, left CSO; 40x20x15 mm³, left DLPFC; 25x20x20 mm³, HP 35x15x15 mm³ and Thal 20x30x15 mm³ using a STEAM sequence (TE/TM/TR=14/33/3000 ms, 128 NEX, 16 NEX water). Spectra were analyzed in LCModel³ using water as an internal reference and a basis set simulated in VESPA⁴. Between group differences were evaluated using student’s t-test, while linear regression analysis (Pearson’s correlation coefficient) was performed for metabolite levels (Gln, Glu, GABA, GSH, NAA, NAAG and Glu/Gln) against test score Statistical significance was set to p < 0.05.A representative spectrum and results of the LCModel curvefit from the CSO in one subject is shown in Figure 1. Figure 2 shows Glu/Gln ratio from 5 regions. Results from t-tests showed significant increase in Gln/Glu in the ACC, CSO and DLPFC (p<0.05), increased Gln in the CSO, DLPFC and Thal, decreased GABA and Glu in the ACC. Significant positive correlations were observed between Glu/Gln in the ACC, CSO, DLPFC and Thal and UPSA-2 Total Score between all subjects (Figure 3). When considering patient population only, correlations were significant between DLPFC Glu/Gln (p<0.05) and UPSA-2 total score. Significant correlations with MCCB composite scores were found between ACC: Glu, NAA, tNAA, CSO, Gln, Glu, Glu/Gln, NAA, tNAA, mI, CSO: tCr, DLPFC: GABA, Gln, Glu/Gln, NAA, tNAA, HP: Ins+Gy, tCr, and Thal: NAAG, and mI for all subjects. This 7T study confirms studies performed at lower field strengths which implicated increased glutamine in psychosis^5,6. Increased Gln and Gln/Glu ratios in multiple brain regions is consistent with the NMDA receptor hypofunction model of schizophrenia, and may be due to several reasons, including possible increased glutamate release into the synaptic cleft (driving Gln synthesis), perturbed glutamate-glutamine cycling between astrocytes and neurons, or astrocytic dysfunction.In addition, significant correlations of Glu/Gln in several brain regions and UPSA-2 and MCCB scores suggest that it has a role in cognition and functional capacity .