Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

BACKGROUND: Disrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse. AIMS: We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC). METHODS: Plasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC. RESULTS: Both the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group. CONCLUSIONS: Compared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.