title: Carbonyl stress in schizophrenia.
abstract: 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.
authors.affiliation: *Project for Schizophrenia and Affective Disorders Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.affiliation: *Project for Schizophrenia and Affective Disorders Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: *Project for Schizophrenia and Affective Disorders Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.affiliation: †United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
mesh_terms: D000818:Animals; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D025101:Vitamin B 6 / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D025101:Vitamin B 6; D007791:Lactoylglutathione Lyase