Accumulating evidence suggests that oxidative stress associated with impaired metabolism of the antioxidant glutathione (GSH) plays a key role in the pathophysiology of schizophrenia. Magnetic resonance spectroscopy (MRS) is one of the brain-imaging techniques that can quantitatively measure bioactive substances such as GSH in the intact human brain. Four different measurement sequences including double quantum coherence (DQC) filtering, MEscher-GArwood Point-RESolved Spectroscopy (MEGA-PRESS), Stimulated Echo Acquisition Mode (STEAM), and PRESS have been used to evaluate the 1H-MRS measurement of GSH in the brains of patients with schizophrenia. Although the results of these studies were somewhat diverse, a negative correlation between brain GSH levels and the severity of negative symptoms in schizophrenia patients suggests that increasing the brain GSH levels might be beneficial for schizophrenia patients with negative symptoms. Moreover, a recent double-blind, placebo-controlled study demonstrated that add-on of N-acetyl-l-cysteine (NAC), a precursor of GSH, to antipsychotics improved the negative symptoms and reduced the side effects (akathisia) in patients with chronic schizophrenia. MRS study of the antioxidant defense system in schizophrenia still remains in the infantile stage; future studies are needed to examine the brain GSH level before and after NAC treatment, and thereby to provide direct evidence of the induced production of GSH in the living brain. Antioxid. Redox Signal. 15, 2057–2065.
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