Glutamatergic and GABAergic systems are believed to play a role in the pathophysiology of psychosis^1,2. This abstract presents results from an interim analysis of an ongoing study the differences in metabolite levels along with metabolite correlations with neuropsychiatric measures in first episode psychosis (FEP) subjects and healthy controls from our on going study. 45 FEP subjects and 70 healthy controls participated in this study to date. All FEP subjects had a diagnosis of psychosis (43.8% schizophrenia) and were recruited within the first two years of disease onset and were on antipsychotic medication at the time of the scan. All participants underwent a set of neuropsychiatric evaluations³ (CNNS), and the FEP subjects also underwent positive and negative symptom rating (SAPS and SANS). MR methods: Participants were scanned using a 7T scanner (Philips ‘Achieva’, Best, Netherlands) equipped with a 32-channel head coil (Nova Medical, Orlando, FL). Spectra were recorded from anterior cingulate cortex (ACC; 30x20x20 mm³, Figure 1), left centrum semiovale (CSO; 40x20x15 mm³), left dorsolateral prefrontal cortex (DLPFC; 25x20x20 mm³), left orbitofrontal cortex (OFC; 20x20x20 mm³), and bilateral thalamus (Thal, 20x30x15 mm³) using a STEAM sequence (TE/TM/TR=14/33/3000 ms, 128 NEX, 16 NEX water). Spectra were analyzed in LCModel⁴ using water as an internal reference and a basis set simulated in VESPA⁵. Statistical analysis: Differences between groups were compared using students t-test, and linear regression performed for GABA, Glu, Gln, GSH, NAA, NAAG, tCr, tCho and tNAA concentrations vs. composite CNNS scores, SAPS and SANS. Representative spectrum from the ACC along with LCModel fit is shown in Figure 1. Metabolite levels that were significantly different between FEP and control subjects are given in Table 1. In patients, significant positive correlations were found between CNNS scores and GABA (p =0.024) , NAAG (p=0.008) and tCho (p=0.017) in the OFC, significant negative correlation between SAPS score and OFC NAA (p=0.039); and significant negative correlation between SANS rating scale and ACC GABA (p=0.042), CSO Glu (p=0.007), CSO Glx (p=0.013) and OFC GABA (p=0.018). Reductions in NAA in FEP in cortical regions and thalamus are consistent with neuronal damage/dysfunction in these regions. In addition, Gln was increased in DLPFC and CSO, Glu decreased in ACC, and NAAG decreased in CSO, suggesting possible glutamatergic dysfunction in multiple brain regions. Glutamatergic metabolite levels also correlated with measures of disease severity (e.g. the negative correlation of SANS with ACC GABA, CSO Glu, CSO Glx and OFC GABA) further suggesting a central role of these metabolites in the pathophysiology of psychosis. However, a larger sample size and further analyses are required to confirm these interim findings.