Clinical Features of Schizophrenia With Enhanced Carbonyl Stress

Abstract

Accumulating evidence suggests that advanced glycation end products, 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 disease. Pyridoxamine is one of the 3 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 advanced glycation end products, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. However, there is as yet no clinical characterization of this subset of schizophrenia. In this study, we found that these patients shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, low educational status, longer durations of hospitalization, and higher doses of antipsychotic 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.

Advanced glycation end products and schizophrenia: A systematic review

“…They showed that schizophrenia patients with accumulated pentosidine and depleted pyridoxal showed distinct clinical features, such as a higher propensity to inpatient status, low educational status, a higher frequency and longer durations of hospitalization and higher doses of anti-psychotic medication compared with patients without oxidative stress (Miyashita et al, 2014a). Based on these results, Kouidrat et al investigated AGE levels as determined by a noninvasive skin autofluorescence method (skin AF) in schizophrenia patients.…”

Genetic analysis of the glyoxalase system in schizophrenia

“…Based on the analysis of biomarkers for carbonyl stress in Japanese patients, Itokawa's group estimated that carbonyl stress might contribute to~20% of schizophrenia (Arai et al, 2010;Itokawa et al, 2014). This subset of patients shared clinical phenotypes seen in treatment-resistant schizophrenia, such as longer hospitalization, a higher proportion of inpatients, demand for higher doses of antipsychotics and lower educational status (Miyashita et al, 2014a). Several rare causal variations in GLOI have been identified in schizophrenia patients with enhanced carbonyl stress (Itokawa et al, 2014); however, the proportion of cases attributable to rare variants should be relatively small.…”

“…In addition, limited data on the clinical phenotypes such as those specific for the subset of schizophrenia cases with carbonyl stress (Miyashita et al, 2014a) restricted us from further evaluating the genetic association with detailed phenotypes. In addition, other members of the glyoxalase system can contribute to the carbonyl stress phenotype such as glutathione synthesis pathway (Thornalley, 1998).…”

Cutting‐edge morphological studies of post‐mortem brains of patients with schizophrenia and potential applications of X‐ray nanotomography (nano‐CT)

“…By taking into account that the distal neurites in the schizophrenia cases showed high curvatures, it was concluded that neurites distal from the soma had become thin and tortuous in schizophrenia. The schizophrenia case that exhibited the highest neurite curvature (the purple line in Figure a) carried a frameshift mutation in the GLO1 gene and has been reported to be resistant to treatment . This schizophrenia patient may have sustained neurite thinning damage from peculiar metabolic disturbances, called ‘carbonyl stress,’ due to the GLO1 gene mutation .…”