Compromised white matter has been reported in schizophrenia; however, few studies have investigated the neurochemical abnormalities underlying these microstructural differences. N-acetylaspartate is often reduced in persons with schizophrenia (SZ) and their unaffected first-degree relatives (REL) and is a potential mechanism underlying these white matter abnormalities. We used a combined MRS-DTI approach to investigate the relationship between NAA and white matter integrity in SZ, REL, and healthy controls (HC).49 HC, 23 REL and 23 SZ underwent 7T proton magnetic resonance spectroscopy and 3T diffusion tensor imaging. NAA concentrations in the visual cortex and basal ganglia were measured and compared across groups. Tract-based spatial statistics were used to derive and compare fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) across groups. NAA concentrations were then correlated to these measures whilst controlling for age and voxel tissue composition.Visual cortex NAA was significantly reduced in SZ compared to HC but not REL. No group differences were observed in any measure of white matter integrity. Reduced NAA concentrations in the visual cortex and basal ganglia correlated with diffusivity measures that were generally consistent with poor white matter microstructure. These data suggest that NAA concentrations may be related to white matter integrity.
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