Enhanced carbonyl stress in a subpopulation of schizophrenia.

CONTEXT: Various factors are involved in the pathogenesis of schizophrenia. Accumulation of advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase in reactive carbonyl compounds (RCOs) and their attendant protein modifications. Vitamin B(6) is known to detoxify RCOs, including advanced glycation end products. Glyoxalase I (GLO1) is one of the enzymes required for the cellular detoxification of RCOs. OBJECTIVES: To examine whether plasma levels of pentosidine and serum vitamin B(6) are altered in patients with schizophrenia and to evaluate the functionality of GLO1 variations linked to concomitant carbonyl stress. DESIGN: An observational biochemical and genetic analysis study. SETTING: Multiple centers in Japan. PARTICIPANTS: One hundred six individuals (45 schizophrenic patients and 61 control subjects) were recruited for biochemical measurements. Deep resequencing of GLO1 derived from peripheral blood or postmortem brain tissue was performed in 1761 patients with schizophrenia and 1921 control subjects. MAIN OUTCOME MEASURES: Pentosidine and vitamin B(6) concentrations were determined by high-performance liquid chromatographic assay. Protein expression and enzymatic activity were quantified in red blood cells and lymphoblastoid cells using Western blot and spectrophotometric techniques. RESULTS: We found that a subpopulation of individuals with schizophrenia exhibit high plasma pentosidine and low serum pyridoxal (vitamin B(6)) levels. We also detected genetic and functional alterations in GLO1. Marked reductions in enzymatic activity were associated with pentosidine accumulation and vitamin B(6) depletion, except in some healthy subjects. Most patients with schizophrenia who carried the genetic defects exhibited high pentosidine and low vitamin B(6) levels in contrast with control subjects with the genetic defects, suggesting the existence of compensatory mechanisms. CONCLUSIONS: Our findings suggest that GLO1 deficits and carbonyl stress are linked to the development of a certain subtype of schizophrenia. Elevated plasma pentosidine and concomitant low vitamin B(6) levels could be the most cogent and easily measurable biomarkers in schizophrenia and should be helpful for classifying heterogeneous types of schizophrenia on the basis of their biological causes.

Spatio-temporal disintegration of visual perception in schizophrenia as revealed by a novel cognitive task, the Searchlight Test.

We developed a novel computer-assisted psychological test (the Searchlight Test) in order to explore 'cognitive fragmentation' and its relation to thought disorder in schizophrenic patients. Participants were instructed to search geometric figures through a small hole (3 cm in diameter) on a display monitor by moving a mouse device and to reconstruct an image of the whole from the temporally and spatially fragmented visual stimuli.The cognitive function measures in 24 schizophrenic patients and 14 normal controls showed that the error rates of the recall task (drawing the figure from memory) and the recognition task (selecting the correct figure from several similar figures) were significantly higher in schizophrenic patients than in normal controls. The error rates of both tasks significantly correlated with disorganization syndrome in schizophrenia, but not with reality distortion or with psychomotor poverty syndrome.The present data obtained with the Searchlight Test suggest the spatio-temporal disintegration of visual perception in schizophrenia and its correlation with disorganization. This test appears to provide a useful tool for studying the pathophysiology of disorganization syndrome, thought disorder and the related cognitive dysfunction of schizophrenia.