Dysfunction of the metabolic system as carbonyl stress: research on medication using vitamin B6 as low physical burden supplement for schizophrenic patients

Abstract

Accumulating evidence suggests that Advanced Glycation End products (AGEs), generated as a consequence of facilitated carbonyl stress, are implicated in the development of a variety of diseases. These diseases include neurodegenerative illnesses, such as Alzheimer’s disease. Pyridoxamine is one of the three forms of vitamin B6 and it acts by combating carbonyl stress and inhibiting the formation of AGEs. Depletion of pyridoxamine due to enhanced carbonyl stress eventually leads to a decrease in the other forms of vitamin B6, namely pyridoxal and pyridoxine. We previously reported that higher levels of plasma pentosidine, a well known biomarker for AGEs, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. In addition, we validated the replication of this metabolic abnormality in the new large cohort. Furthermore, we found that these patients shared many clinical features with treatment resistant schizophrenia, as defined by Kane et al. These features include a higher proportion of in-patients, low educational status, longer durations of hospitalization, and higher doses of anti-psychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients.