[Carbonyl stress-related schizophrenia--perspective on future therapy and hypotheses regarding pathophysiology of...

Various factors are thought to be involved in the pathogenesis of schizophrenia. Recently, biochemical studies using human samples and animal models suggest that oxidative stress and the resulting formation of reactive carbonyl compounds (RCOs) contribute to the pathophysiology of schizophrenia. The accumulation of RCOs, carbonyl stress, results in the modification of proteins and formation of advanced glycation end products (AGEs), such as pentosidine. We previously reported that a certain subtype of schizophrenic patients exhibit idiopathic carbonyl stress with high plasma pentosidine levels and the depletion of vitamin B6, without underlying diabetes or chronic kidney disease, the two major causes of elevated AGEs. Agents able to inhibit AGE formation or entrap carbonyl compounds may also prove to be of therapeutic value. Pyridoxamine, a non-toxic, water-soluble vitamin B6, has potent abilities to entrap toxic carbonyl compounds and prevent toxicity. In particular, the markedly lowered vitamin B6 levels in schizophrenic patients with high pentosidine levels suggest that pyridoxamine may prove to be clinically useful.