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Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels

Published online by Cambridge University Press:  27 January 2014

A. R. Rosa ,
N. Singh ,
E. Whitaker ,
M. de Brito ,
A. M. Lewis ,
E. Vieta ,
G. C. Churchill ,
J. R. Geddes  and
G. M. Goodwin
A. R. Rosa
Affiliation:
Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Spain Department of Pharmacology, University of Oxford, Oxford, UK Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
N. Singh*
Affiliation:
Department of Pharmacology, University of Oxford, Oxford, UK
E. Whitaker
Affiliation:
Department of Pharmacology, University of Oxford, Oxford, UK
M. de Brito
Affiliation:
Department of Pharmacology, University of Oxford, Oxford, UK
A. M. Lewis
Affiliation:
Department of Pharmacology, University of Oxford, Oxford, UK
E. Vieta
Affiliation:
Bipolar Disorders Program, Institute of Neurosciences, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Spain
G. C. Churchill
Affiliation:
Department of Pharmacology, University of Oxford, Oxford, UK
J. R. Geddes
Affiliation:
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
G. M. Goodwin
Affiliation:
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK
*
*Address for correspondence: Dr N. Singh, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. (Email: nisha.singh@pharm.ox.ac.uk)
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Abstract

Background

Oxidative stress and neurotrophic factors have been implicated in the pathophysiology of bipolar disorder. Our objective was to determine whether plasma glutathione or brain-derived neurotrophic factor (BDNF) levels were abnormal in bipolar disorder and therefore useful as possible biomarkers.

Method

Blood samples were collected from subsyndromal, medicated bipolar I patients (n = 50), recruited from OXTEXT, University of Oxford, and from 50 matched healthy controls. Total and oxidized glutathione levels were measured using an enzymatic recycling method and used to calculate reduced, percentage oxidized, ratio of reduced:oxidized and redox state. BDNF was measured using an enzyme-linked immunoassay. Self-monitored mood scores for the bipolar group were available (Quick Inventory of Depressive Symptomatology and the Altman Self-Rating Mania Scale) over an 8-week period.

Results

Compared with controls, bipolar patients had significantly lower levels of total glutathione and it was more oxidized. BDNF levels were not different. Age of illness onset but not current mood state correlated with total glutathione levels and its oxidation status, so that lower levels of total and reduced glutathione were associated with later onset of disease, not length of illness.

Conclusions

Plasma glutathione levels and redox state detect oxidative stress even in subsyndromal patients with normal BDNF. It may relate to the onset and development of bipolar disorder. Plasma glutathione appears to be a suitable biomarker for detecting underlying oxidative stress and for evaluating the efficacy of antioxidant intervention studies.

Keywords

Bipolar disorderbrain-derived neurotrophic factordepressionglutathionemoodoxidative stress
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 11 , August 2014 , pp. 2409 - 2418
Copyright
Copyright © Cambridge University Press 2014 

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