Association of homocysteine with white matter dysconnectivity in schizophrenia

Abstract

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman's ρ = -.330, P = 0.016) but not in the HC group (Spearman's ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

Fig. 1. Areas with significant fractional anisotropy (FA) reduction in individuals with schizophrenia (SZ).

Individuals with SZ exhibited FA reductions in areas such as the bilateral frontal, temporal, parietal, and occipital lobes, a large portion of the corpus callosum, and the corona radiata. To aid visualization, results were thickened using the tbss_fill script implemented in FSL (red-yellow). Statistical significance was set at P < 0.05, corrected by threshold-free cluster enhancement.

Fig. 2. Correlation between homocysteine (Hcy) and white matter dysconnectivity.

a The schizophrenia (SZ) group showed a statistically significant negative correlation between plasma Hcy levels and mean fractional anisotropy (FA) of the clusters with significant FA differences between the SZ and HC groups. b No correlation was found in healthy controls (HC). To aid visualization, Spearman’s rank orders are shown on both the X and Y axes. The regression line is shown on each graph. The filled markers and solid regression lines indicate significant results, and open markers and broken lines indicate non-significant results.