Polyunsaturated fatty acid concentration predicts myelin integrity in early-phase psychosis

Abstract

Background: White matter (WM) abnormalities have been implicated in schizophrenia, yet the mechanisms underlying these abnormalities are not fully understood. Several lines of evidence suggest that polyunsaturated fatty acids (PUFAs) play a role in myelination, and there is substantial evidence documenting decreased PUFA concentrations in schizophrenia. We therefore hypothesized that lower membrane PUFA concentrations may be related to reduced WM integrity in schizophrenia and related disorders.

Methods: In 30 male patients with a recent-onset psychotic disorder, erythrocyte membrane PUFA concentrations were assessed and diffusion tensor imaging was performed with voxelwise analysis.

Results: Lower total PUFA concentration was associated with lower fractional anisotropy (FA) throughout the corpus callosum and bilateral parietal, occipital, temporal and frontal WM (P < .05, corrected). Of the individual PUFAs, lower arachidonic acid concentration, and to a lesser extent, lower nervonic acid, linoleic acid, and docosapentaenoic acid concentration were significantly associated with lower FA. PUFA concentrations were inversely associated with radial diffusivity but showed little association with axial diffusivity. Greater severity of negative symptoms was associated with lower nervonic acid concentration and lower FA values.

Conclusions: Membrane PUFA concentrations appear to be robustly related to brain WM integrity in early phase psychosis. These findings may provide a basis for studies to investigate the effects of PUFA supplementation on WM integrity and associated symptomatology in early psychosis.

Keywords: diffusion tensor imaging; first-episode psychosis; myelin; polyunsaturated fatty acids; schizophrenia; white matter.

Fig. 1.

Clusters showing significant positive correlations between (poly)unsaturated acid concentrations in erythrocyte membranes and white matter (WM) fractional anisotropy in 30 patients with a recent-onset psychotic disorder. Panel A: Results for total (poly)unsaturated fatty acids. Panel B: Results for arachidonic acid. Significant voxels (P < 0.05, corrected) are colored, “thickened” by filling them out into the local tracts, and overlaid on the mean WM skeleton (green) and the FMRIB58 FA template, for display purposes.

Fig. 2.

Correlations between (poly)unsaturated fatty acid concentrations in erythrocyte membranes and white matter (WM) fractional anisotropy in 30 patients with a recent-onset psychotic disorder. Top panel: Significant correlation between total (poly)unsaturated fatty acid concentration and fractional anisotropy in a large WM cluster comprised of 16 441 voxels, centered in the corpus callosum and extending into parietal, occipital, temporal and frontal WM (r _s = 0.636, P < 0.001). Bottom panel: Significant correlation between arachidonic acid concentration and fractional anisotropy in a large WM cluster comprised of 5 950 voxels, centered in the corpus callosum and extending into parietal, occipital, temporal and frontal WM (r _s = 0.544, P = 0.002).