1. ¹Department of Psychiatry, ORYGEN Research Centre, University of Melbourne, Parkville, Australia
2. ²Department of Research & Education, The Schloessli Clinic, Oetwil am See, Zuerich, Switzerland
3. ³Howard Florey Institute, The University of Melbourne, Parkville, Australia
4. ⁴Department of Psychiatry, University of Melbourne, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Parkville, Australia
5. ⁵Brain Research Institute, Heidelberg, Australia
6. ⁶Queensland University of Technology, Brisbane, Australia

Correspondence: Dr GE Berger, Department of Psychiatry, University Hospital Basel, Petersgraben 4, Basel, Basel-Stadt 4031, Switzerland. Tel: 41612655040; Fax; 41612654588; E-mail: bergerg@mac.com

Received 11 May 2007; Revised 5 September 2007; Accepted 15 October 2007; Published online 16 January 2008.

Abstract

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.