We have identified idiopathic carbonyl stress in a subpopulation of schizophrenic patients. We first identified a patient with a mutation in GLO1 (glyoxalase I) who showed increased AGE (advanced glycation end-product) levels and decreased vitamin B6 levels. By applying the observations from this rare case to the general schizophrenic population, we were able to identify a subset of patients (20%) for whom carbonyl stress may represent a causative pathophysiological process. Genetic defects in GLO1 increase the risk of carbonyl stress 5-fold, and the resulting increased AGE levels correlate significantly with PANSS (Positive and Negative Syndrome Scale) scored negative symptoms. Pyridoxamine, an active form of vitamin B6 and scavenger for carbonyl stress, could represent a novel and efficacious therapeutic agent for these treatment-resistant symptoms. In the present article, we describe a unique research approach to identify the causative process in the pathophysiology of a subset of schizophrenia. Our findings could form the basis of a schizophrenia subtype classification within this very heterogeneous disease and ultimately lead to better targeted therapy.
- advanced glycation end-product (AGE)
- carbonyl stress
- glyoxalase I
- vitamin B6
Glyoxalase Centennial: 100 Years of Glyoxalase Research and Emergence of Dicarbonyl Stress: A Biochemical Society Focused Meeting held at the University of Warwick, U.K., 27–29 November 2013. Organized and Edited by Naila Rabbani and Paul Thornalley (University of Warwick, U.K.).
Abbreviations: AGE, advanced glycation end-product; Glo1, glyoxalase I; PANSS, Positive and Negative Syndrome Scale
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