Carbonyl stress suggests strategy for treatment-resistant schizophrenia

By Eleanor McDermid, Senior medwireNews Reporter

Patients with schizophrenia who have enhanced carbonyl stress have clinical features associated with treatment resistance, say researchers.

Mitsuhiro Miyashita (Tokyo Metropolitan Institute of Medical Science, Japan) and team used two biomarkers to identify patients with carbonyl stress: high plasma pentosidine (>62.9 ng/ml) and low pyridoxal levels (<6 ng/ml in men, <4 ng/ml in women). Pyridoxal was representative of vitamin B6 (pyridoxamine).

Noting that current medications with the most success in treatment-resistant schizophrenia also carry the most severe adverse effects, the researchers say their findings “support the idea that simple treatments that reduce carbonyl stress, such as supplementation of pyridoxamine, may be of novel therapeutic benefit for this subset of patients.”

In all, 26 of the 163 patients in the study had both high pentosidine and low pyridoxal levels, and these patients had several clinical characteristics that were significantly more severe than those of the 67 patients with normal levels of both biomarkers, consistent with treatment-resistant schizophrenia.

Specifically, 80.8% versus 23.9% were inpatients, their average length of hospitalization was 17.4 years compared with 4.2 years, and they were taking a significantly higher dose of antipsychotic medication. They also had a significantly shorter duration of education, at 11.7 versus 13.0 years.

“Intriguingly, the 2 groups consisting of patients with either high pentosidine or low pyridoxal levels… exhibited clinical features that were almost intermediate” between the other two groups, reports the team in Schizophrenia Bulletin.

For all groups combined, lower pyridoxal levels significantly correlated with higher total Positive and Negative Syndrome Scale scores, and also with the total positive symptom and total general psychopathology subscale scores.

“Although, the precise mechanisms of decreased pyridoxal levels in patients with enhanced carbonyl stress are not fully understood, our observations strongly support the theory that supplementation of vitamin B6 for these patients may safely improve specific clinical symptoms associated with pyridoxal levels,” say Miyashita et al.

They note that studies of vitamin B6 supplementation in schizophrenia have been inconclusive, and suggest that benefits may be limited to patients who have low vitamin B6 levels in combination with carbonyl stress.

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