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Effect of interferon-α on cortical glutamate in patients with hepatitis C: a proton magnetic resonance spectroscopy study

Published online by Cambridge University Press:  10 May 2013

M. J. Taylor ,
B. Godlewska ,
J. Near ,
D. Christmas ,
J. Potokar ,
J. Collier ,
P. Klenerman ,
E. Barnes  and
P. J. Cowen
M. J. Taylor*
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
B. Godlewska
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK
J. Near
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK FMRIB Centre, Department of Clinical Neurology, University of Oxford, UK
D. Christmas
Affiliation:
Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, UK
J. Potokar
Affiliation:
Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, UK
J. Collier
Affiliation:
John Radcliffe Hospital, Oxford, UK
P. Klenerman
Affiliation:
NIHR Oxford Biomedical Research Centre, UK The Peter Medawar Building for Pathogen Research, University of Oxford, UK
E. Barnes
Affiliation:
NIHR Oxford Biomedical Research Centre, UK The Peter Medawar Building for Pathogen Research, University of Oxford, UK
P. J. Cowen
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK
*
* Address for correspondence: Dr M. J. Taylor, Department of Psychosis Studies, Institute of Psychiatry, PO63, London SE5 8AF, UK. (Email: [email protected])
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Abstract

Background

The development of depressive symptomatology is a recognized complication of treatment with the cytokine interferon-α (IFN-α) and has been seen as supporting inflammatory theories of the pathophysiology of major depression. Major depression has been associated with changes in glutamatergic activity and recent formulations of IFN-induced depression have implicated neurotoxic influences that could also lead to changes in glutamate function. The present study used magnetic resonance spectroscopy (MRS) to measure glutamate and its major metabolite glutamine in patients with hepatitis C who received treatment with pegylated IFN-α and ribavirin.

Method

MRS measurements of glutamate and glutamine were taken from a 25 × 20 × 20 mm voxel including the pregenual anterior cingulate cortex in 12 patients before and after 4–6 weeks of treatment with IFN.

Results

IFN treatment led to an increase in cortical levels of glutamine (p = 0.02) and a significant elevation in the ratio of glutamine to glutamate (p < 0.01). Furthermore, changes in glutamine level correlated significantly with ratings of depression and anxiety at the time of the second scan.

Conclusions

We conclude that treatment with IFN-α is associated with MRS-visible changes in glutamatergic metabolism. However, the changes seen differ from those reported in major depression, which suggests that the pathophysiology of IFN-induced depression may be distinct from that of major depression more generally.

Keywords

Depressionglutamateglutaminehepatitis Cinterferon-α
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 4 , March 2014 , pp. 789 - 795
Copyright
Copyright © Cambridge University Press 2013 

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