Polyunsaturated fatty acids and brain white matter anisotropy in recent-onset schizophrenia: A preliminary study

doi:10.1016/j.plefa.2009.04.007

Prostaglandins, Leukotrienes and Essential Fatty Acids

Volume 81, Issue 1, July 2009, Pages 61-63

https://doi.org/10.1016/j.plefa.2009.04.007 Get rights and content

Abstract

Brain white matter myelin abnormalities and cell membrane fatty acid abnormalities have been implicated in schizophrenia and other psychiatric disorders. We investigated in young adults with a psychotic disorder (n=12) whether (poly)unsaturated fatty acid concentrations in erythrocyte membranes are related to an MRI measure of brain white matter, which depends on the degree of myelination. A significant correlation was found between total (poly)unsaturated fatty acid concentration and fractional anisotropy of a fronto-temporal white matter tract (r=0.503, P=0.048). Unsaturated fatty acids may be necessary for the myelinating activity of oligodendrocytes or for myelin maintenance. These results warrant further investigation.

Introduction

The pathophysiology of schizophrenia may involve a disturbance in myelination resulting in compromised connectivity between neurons and brain regions [1]. Myelin abnormalities in brain white matter have been found in vivo with T2 relaxation MRI, and abnormalities of oligodendrocytes, which form the myelin sheaths around axons, have been determined postmortemly [2]. Another MRI technique called diffusion tensor imaging (DTI) has also shown microstructural white matter abnormalities in schizophrenia [3]. In DTI, anisotropic diffusion of water along the length of axons is measured as an indication of white matter integrity. Intact axonal membranes form the basis for white matter anisotropy [4], and myelination increases the degree of anisotropy [5].

Demyelination in peroxisomal disorders is related to unsaturated fatty acid deficiency, which can be corrected with dietary supplementation of fatty acids [6]. Myelin sheaths are formed from the membranes of oligodendrocytes and decreased membrane fatty acid concentrations may contribute to disturbed myelination. Decreased (poly)unsaturated fatty acid concentrations have been found in schizophrenia at illness onset [7] and prior to the start of medication treatment [8]. These abnormalities may reflect a pathophysiological mechanism in schizophrenia with both environmental and genetic contributions [9].

We hypothesized that in schizophrenia patients (poly)unsaturated fatty acid concentration in erythrocytes, which reflects membrane phospholipid metabolism in the brain [10], [11], is positively correlated to brain white matter anisotropy measured with DTI.

Section snippets

Subjects

Twelve male patients (mean age 22.7±2.7 years) from the Adolescent Clinic of the Academic Medical Center, Amsterdam, diagnosed with a recent onset of schizophrenia or related disorder, were included after the clinical condition had stabilized. All patients received antipsychotic medication (median duration 20.6 weeks, range 2.7–83.7; median dose at MRI in haloperidol equivalents 2, range 0.67–7.3). Only one patient used a typical antipsychotic; six patients used olanzapine, three risperidone,

Results and discussion

Total pufa concentration (mean 287.0±81.7 pmol/10e6 cells) was positively correlated to fractional anisotropy in the bilateral uncinate fasciculus (r=0.503, P=0.048; see Fig. 1). No significant correlations were observed for the other ROIs.

These findings give support to our hypothesis that membrane (poly)unsaturated fatty acid concentration is related to white matter microstructure in schizophrenia. Decreased (poly)unsaturated fatty acid concentrations may negatively influence myelination.

The

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Citation Excerpt :
These longitudinal findings provide preliminary evidence that concomitant administration of n-3 PUFAs may mitigate changes in white matter microstructural measures observed in recent-onset psychosis patients treated with risperidone. Our findings are consistent with studies implicating a potential role for PUFA biosynthesis in compromised white matter previously observed in psychosis patients (Peters et al., 2009, 2013). In the present study, the positive correlations between n-3 PUFA levels at baseline, specifically DHA and DPA, and the traditional DTI metric, FA, replicate prior work (Peters et al., 2009, 2013).
We examined the impact of treatment with fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids (n-3 PUFA), on white matter in 37 recent-onset psychosis patients receiving risperidone in a double-blind placebo-controlled randomized clinical trial. Patients were scanned at baseline and randomly assigned to receive 16-weeks of treatment with risperidone + FO or risperidone + placebo. Eighteen patients received follow-up MRIs (FO, n = 10/Placebo, n = 8). Erythrocyte levels of n-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) were obtained at both time points. We employed Free Water Imaging metrics representing the extracellular free water fraction (FW) and fractional anisotropy of the tissue (FA-t). Analyses were conducted using Tract-Based-Spatial-Statistics and nonparametric permutation-based tests with family-wise error correction. There were significant positive correlations of FA-t with DHA and DPA among all patients at baseline. Patients treated with risperidone + placebo demonstrated reductions in FA-t and increases in FW, whereas patients treated with risperidone + FO exhibited no significant changes in FW and FA-t reductions were largely attenuated. The correlations of DPA and DHA with baseline FA-t support the hypothesis that n-3 PUFA intake or biosynthesis are associated with white matter abnormalities in psychosis. Adjuvant FO treatment may partially mitigate against white matter alterations observed in recent-onset psychosis patients following risperidone treatment.
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^☆: This study was funded by Grant 28-1241-2 from the Dutch Health Research and Development (ZONMw).

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Polyunsaturated fatty acids and brain white matter anisotropy in recent-onset schizophrenia: A preliminary study☆

Abstract

Introduction

Section snippets

Subjects

Results and discussion

Neuropsychopharmacology

Biol. Psychiatry

Biol. Psychiatry

Prostaglandins Leukot. Essent. Fatty Acids

Prog. Neuropsychopharmacol. Biol. Psychiatry

Biol. Psychiatry

J. Lipid Res.

Schizophr. Res.

Prostaglandins Leukot. Essent. Fatty Acids

Biol. Psychiatry

Neuroimage

Am. J. Clin. Nutr.

Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins

Mol. Psychiatry

The basis of anisotropic water diffusion in the nervous system—a technical review

NMR Biomed.