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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.

Alterations of polyunsaturated fatty acids (PUFA) in schizophrenia have been reported, but there is substantial variation in the findings. We performed a systematic review and meta-analysis for docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), linoleic acid (LA), and arachidonic acid (AA). We identified 18 studies which compared PUFA in the erythrocyte cell membrane between patients with schizophrenia and controls. A total of 642 patients (169 were antipsychotic-naïve) and 574 controls participated in these studies. We found suggestive evidence that the levels of DPA (C22:5n3) and DHA (C22:6n3) are decreased both in patients currently being treated with antipsychotic medication and antipsychotic-naïve patients. Our findings furthermore suggest that the levels of LA (C18:2n6) are decreased in the medicated subgroup, but not in the antipsychotic-naive group. Finally, we found decreased levels of AA (C20:4n6), most convincingly in antipsychotic-naive patients. Taken together, there is substantial evidence that decreased levels of DPA (C22:5n3), DHA (C22:6n3), and AA (C20:4n6) are associated with the schizophrenia syndrome, apart from a possible influence of antipsychotic medication. Given the large heterogeneity in results, these conclusions should be interpreted cautiously., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)