Significance of measurements of peripheral carbonyl stress markers in a cross-sectional and longitudinal study in patients with acute-stage schizophrenia

Abstract

Altered peripheral carbonyl stress markers, high levels of serum pentosidine, which accumulates following carbonyl stress, and low levels of pyridoxal (vitamin B6), which detoxifies reactive carbonyl compounds, have been reported in a cross-sectional study of chronic schizophrenia. However, changes in the levels of these compounds in patients with schizophrenia have not been investigated in a longitudinal study. To clarify whether these markers may be biological markers that reflect the clinical course of the disease, the serum levels of these compounds were investigated in a cross-sectional and a longitudinal study. One hundred and thirty-seven acute-stage Japanese patients were enrolled. Among these, 53 patients were followed from the acute stage to remission. A portion of patients in the acute stage (14 cases, 10.2%) showed extremely high pentosidine levels. These levels were not associated with the severity of symptoms but were associated with antipsychotic dose amounts. Pyridoxal levels were lower in schizophrenia and increased according to the clinical course of the illness. Furthermore, 18 patients with decreased pyridoxal levels according to the clinical course showed that the greater the decrease in pyridoxal levels, the lesser the improvement in symptoms. Thus, extremely high pentosidine levels in a portion of patients may be caused by higher daily antipsychotic doses, whereas pyridoxal levels were lower in schizophrenia and increased according to the clinical course. Patients with decreasing pyridoxal levels during the clinical course showed less improvement in symptoms. Carbonyl stress markers may also be therapeutic biological markers in some patients with schizophrenia.

Keywords: clinical course; pentosidine; pyridoxal; vitamin B6.

Fig. 1.

Mechanism of carbonyl stress and its detoxification with vitamin B6 and glyoxalase. Reactive carbonyl compounds (RCOs), which cause carbonyl stress, are detoxified by degradation into lactic acid and glutathione by glyoxalase enzymes. Glyoxalase 1 and 2 (GLO1 and GLO2) are the rate-limiting enzymes in this metabolic pathway. Inhibition of RCO generation and the Maillard reaction by vitamin B6 results in the suppression of AGE accumulation. This figure is adapted from 2 previous publications, with partial modification.^,

Fig. 2.

Serum levels of carbonyl stress markers in normal controls and patients with schizophrenia at admission. A. Pentosidine. B. Pyridoxal. Fourteen patients with high pentosidine (>2 SD higher than the mean in controls, >57.6ng/ml) are indicated with an asterisk. Values were compared with the 2-tailed Mann-Whitney U test. Error bars indicate mean and standard deviations.

Fig. 3.

Changes in serum carbonyl stress markers in paired-sample patients with schizophrenia (n = 53) who were followed from the time of admission to discharge. Dotted lines indicate a decrease in carbonyl stress (decrease in pentosidine and increase in pyridoxal), and solid lines indicate an increase in carbonyl stress (increase in pentosidine and decrease in pyridoxal) over time.