The International Journal of Neuropsychopharmacology

Research Article

Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders

Jeremy W. Gawryluka1, Jun-Feng Wanga1, Ana C. Andreazzaa1, Li Shaoa1 and L. Trevor Younga1 c1

a1 Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

Abstract

Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. The aim of this study was to determine if mood disorders and SCZ are associated with abnormal GSH and its functionally related enzymes. Post-mortem prefrontal cortex from patients with BD, MDD, SCZ, and from non-psychiatric comparison controls were provided by the Stanley Foundation Neuropathology Consortium. Spectrophotometric analysis was utilized for the quantitative determination of GSH, while immunoblotting analyses were used to examine expression of glutamyl-cysteine ligase (GCL), GSH reductase (GR), and GSH peroxidase (GPx). We found that the levels of reduced, oxidized, and total GSH were significantly decreased in all psychiatric conditions compared to the control group. Although GCL and GR levels did not differ between groups, the levels of GPx were reduced in MDD and SCZ compared to control subjects. Since oxidative damage has been demonstrated in MDD, BD, and SCZ, our finding that GSH levels are reduced in post-mortem prefrontal cortex suggests that these patient groups may be more susceptible to oxidative stress.

(Received March 08 2010)

(Reviewed April 09 2010)

(Revised April 30 2010)

(Accepted June 03 2010)

(Online publication July 16 2010)

Correspondence:

c1 Address for correspondence: Dr L.T. Young, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T2A1. Tel.: (604)822-7310 Fax: (604)822-0399 Email: Trevor.Young@ubc.ca