Role of glia in prefrontal white matter abnormalities in first episode psychosis or mania detected by diffusion tensor spectroscopy.

BACKGROUND: White matter (WM) abnormalities are amongst the most commonly described neuroimaging findings in patients with psychotic disorders including schizophrenia (SZ) and bipolar disorder (BD), and may be central to pathophysiology. Few studies have directly compared WM abnormalities in patients with SZ and BD in the first episode of illness, and no studies to date have attempted to separate abnormalities of axon and myelin using complementary MRI techniques. METHODS: We examined WM abnormalities in young adults with SZ (n = 19) or BD (n = 16) within the first year of illness onset, and healthy controls (n = 22) using a combination of diffusion tensor spectroscopy to measure NAA, creatine (Cr), and choline (Cho), and magnetization transfer ratio (MTR). MTR reflects myelin content, NAA diffusion is neuron specific, and Cr and Cho diffusion reflect both neuron and glial signal. RESULTS: We found no differences in MTR or NAA ADC in either patient group compared to controls, but significant elevations of both Cr and Cho diffusion in patients with SZ, and elevations of Cho diffusion in patients with BD. Elevations in Cr and Cho diffusion in the absence of NAA diffusion abnormalities indicate that the aberrant signal arises in glia. CONCLUSIONS: Glial abnormalities were present and detectable by the first episode of psychosis, whereas major abnormalities in axon and myelin were not. Examination of these neurobiological markers early in the course of illness may clarify the neuroprogressive nature of these distinct aspects of WM, and their associations with early clinical phenotypes.