389 Fronto-parietal white matter integrity and neurometabolic profiles in medication-naïve first-episode psychosis

Objectives/Goals: In psychosis spectrum disorders, diffusion tensor imaging studies consistently report reduced fractional anisotropy in the superior longitudinal fasciculus, a major tract linking frontal and parietal cortices, yet the neurochemical underpinnings of these microstructural abnormalities remain poorly understood. Methods/Study Population: We collected diffusion MRI scans and single-voxel PRESS magnetic resonance spectroscopy scans both in parietal and frontal white matter in 48 medication naïve patients and 39 healthy controls. Fractional anisotropy within the superior longitudinal fasciculus was quantified in using TORTOISE and compared with frontal and parietal neurometabolic profiles processed with LC model and partial volume corrected. Results/Anticipated Results: Myoinositol and TNAA were significantly different between patients and controls in both frontal and parietal white matter. Fractional anisotropy of the superior longitudinal fasciculus was significantly different between patients and controls. Both myoinositol and TNAA were associated with superior longitudinal fasciculus fractional anisotropy when modeled independently, but when jointly modeled only TNAA was significantly associated with fractional anisotropy in the parietal white matter while only myoinositol was significant in the frontal white matter. Both parietal and frontal white matter had a significantly greater association between myoinositol and fractional anisotropy than controls. Discussion/Significance of Impact: Disruptions in neuronal integrity and glial dysfunction likely contribute to decreased fractional anisotropy in frontoparietal white matter in first-episode psychosis spectrum disorders. These disturbances are not related to medication effects.