Brief report
Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: A longitudinal T2 relaxometry pilot study

https://doi.org/10.1016/j.pscychresns.2009.12.003Get rights and content

Abstract

We used magnetic resonance imaging to examine the effect of ethyl-eicosapentaenoic acid (E-EPA) on hippocampal T2 relaxation time in first episode psychosis patients at baseline and after 12 weeks of follow-up. There was an increase in T2 in the placebo group but not in the E-EPA group, suggesting a neuroprotective effect of E-EPA treatment. In addition, the smaller the increase in T2, the greater the improvement in negative symptoms.

Introduction

Omega-3 fatty acids (essential fatty acids or EFA) are critical to normal brain functioning (Bazan, 2005, Bazan et al., 1995), and are potential adjunctive treatments for psychotic disorders (Berger et al., 2003). These effects may arise via a number of mechanisms, such as through the incorporation of EFAs into brain cell membranes (Tappia et al., 1997), EFA-induced alteration of neurotransmission (Yao et al., 2004) and EFA-driven reduction of oxidative stress (Lonergan et al., 2002).

Previous neuroimaging studies have shown that treatment with ethyl-eicosapentaenoic acid (E-EPA, an omega-3 fatty acid) may result in significant increases in a marker of neuronal integrity (Frangou et al., 2007) and increased brain antioxidant levels (specifically glutathione Berger et al., 2008). Although the former report was in bipolar disorder and the latter in first episode psychosis, they both suggest a neuroprotective effect of E-EPA mediated by reducing oxidative stress.

One limitation of these studies is that they did not examine the effect of E-EPA on membrane fluidity, or look for subtle regional effects. One way to do this using magnetic resonance imaging is to measure brain water proton transverse relaxation times (T2). T2 is an index of the water present in neuronal tissues, and T2 increases are thought reflective of reduced neuronal health. The method has been extensively used to quantify hippocampal sclerosis in patients with epilepsy (Van Paesschen et al., 1997) and to detect abnormalities in normal-appearing white matter (Neema et al., 2009). Previous work in bipolar disorder showed that treatment with EFAs was associated with T2 reductions across the whole brain (Hirashima et al., 2004) indicative of a neuroprotective action.

Here we present a pilot placebo-controlled study of the effect of E-EPA on hippocampal T2 measures in first episode psychosis patients (FEP). There were two reasons for selecting the hippocampus as our region of interest. First, the hippocampus is known to be involved in schizophrenia, the region has already been shown to be sensitive to EPA in a spectroscopy study (Berger et al., 2008), and the hippocampus may be particularly sensitive to neuroprotective agents because it is one of the few brain areas in which adult neurogenesis occurs. Second, measurement of T2 in the hippocampus is simplified by the fact that the region has clear boundaries, enhancing reliability, and a number of other relevant areas are not measurable because of the sequence design (e.g. posterior regions, orbitofrontal cortex).

Section snippets

Demographic data

All participants were patients of the Early Psychosis Prevention & Intervention Centre (Orygen Youth Health Clinical Program, Melbourne). The Mental Health Research and Ethics Committee (Melbourne Health) approved the study, and inclusion criteria have been reported elsewhere (Berger et al., 2008). Participants were part of a larger randomized, double-blind, placebo-controlled clinical trial (Berger et al., 2007) investigating the augmenting effects of E-EPA

Results

A repeated-measures group × laterality × region × time ANOVA showed a significant main effect of time (F1,15 = 6.19, P = 0.025; follow-up > baseline) and region (F1,15 = 24.69, P < 0.001; head > body), and a trend interaction between time and group (F1,15 = 3.49, P = 0.083). There was no significant effect of laterality (F1,15 = 0.05, P = 0.820), and no three- or four-way interactions (all P > 0.2).

Post hoc analyses were conducted to investigate the interaction trend between time and group (see Table 1). Because of the

Discussion

In this pilot study we examined the effects of E-EPA on hippocampal T2 relaxation time in a group of young FEP patients. Although not reaching significance (most likely because of small groups), effect sizes clearly indicated a large increase in the placebo group that was not seen in the E-EPA group. These findings support a general neuroprotective effect of E-EPA (e.g. Frangou et al., 2007), perhaps through an increase in the antioxidant glutathione and subsequent oxidative stress reduction (

Acknowledgements

This work was supported by two NH&MRC project grants (ID: 145627; 209062), a NH&MRC program grant (ID: 350241), and the Colonial Foundation, Melbourne, Australia. A/Prof Wood is supported by a Clinical Career Development Award from the NH&MRC, and Dr Cocchi by a Swiss National Science Foundation young investigator award (PBLAB3-119622). A Margaret & Walter Lichtenstein Foundation award (University of Basel) supported Dr Berger. These funding sources had no further role in study design; in the

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