158. Female-Specific Excessive Extracellular Free-Water in Prodromal Schizophrenia

Background: Two previous diffusion MRI studies identified widespread excessive extracellular free-water in 2 separate datasets of first-episode schizophrenia patients. Free-water is a diffusion MRI measure that quantifies the fractional volume of water that is free to diffuse, that is, can only be found in extracellular spaces. Additional studies in chronic schizophrenia patients identified very limited or no excessive free-water. While the pathological sources of excessive extracellular free-water are still not known, it is important to understand whether or not such a finding precedes psychosis. To this end, we here investigate free-water abnormalities in prodromal subjects. Methods: The study includes subjects from a single site of the North American Prodromal Longitudinal Study (NAPLS—phase 2). All prodromal subjects with usable diffusion MRI scans were analyzed, resulting in 13 female and 30 male subjects. These subjects were matched to 15 female and 16 male healthy controls from the same site. All data were inspected, masked and preprocessed to correct for motion artifacts. Free-water maps and free-water corrected fractional anisotropy maps (FAt) were calculated. Images were then projected onto a white matter skeleton (TBSS) and groups were compared using voxel wise as well as anatomical regions of interest. Results: Voxel wise comparison of the white matter skeleton showed widespread significantly increased free-water ( P < .05; family-wise error corrected) in female prodromes, but not in males. The average free-water was significantly higher for females ( P = .002) but nonsignificantly higher for males ( P = .78). There were no significant changes in FAt. Post-hoc ROI comparisons revealed significant free-water increases (t-test; P < .05) in the cingulum (CG), internal capsule, posterior thalamic radiation, superior longitudinal fasciculus (SLF) and striatum of female patients. The free-water values in the CG and SLF were positively correlated (Spearman correlation; P < .05) with the SOPS measure of general symptoms. Conclusion: We identified a female-specific increase in extracellular free-water in prodromal patients, which was correlated with general symptoms. This finding agrees with our previous findings in first-episode subjects, where free-water increases were more pronounced in females than in males. Increased free-water could be related to neuroinflammation, which might be hormonal mediated, and manifested in general symptoms such as slee