[Molecular pathophysiology of schizophrenia and preventive strategy in pubertal period]

A novel frameshift mutation in glyoxalase 1 (GLO1) gene was detected in a patient with schizophrenia of a pedigree with multiple affected individuals. The patient carrying the mutation showed decreased enzymatic activity by 50%, 3.7 times high level of advanced glycation end products (AGEs) that is substrate of GLO1 and 20% of serum vitamin B6 compared to controls. Case-control study of GLO1 gene suggested that Ala allele of Glu111Ala was associated with schizophrenia. In vitro study using COS-7 cells transfected with cDNA of GLO1 yielded that enzymatic activity is lower in GLO1 with Ala111 than that of Glu111. The homozygotes of Ala111 showed 16% decreased GLO1 activities in RBC as compared with that of Glu111/Ala111 and Glu111/Glu111. Plasma AGEs levels were significantly high and serum vitamin B6 was significantly low in 45 schizophrenics than that of 61 control subjects. Supplementation of vitamin B6 to cases with the genetic defect of GLO1 before onset of psychosis is suggested to be possible strategy for prevention of schizophrenia until pubertal stage since such mutation carriers could have been exposed by high level of AGEs for a long time before disease onset.