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.

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

“…Psychotic patients in general are in a significantly increased longterm con dition of oxidative stress [102,103] . Oxidative stress markers, such as pentosidine [104] , glycer-AGE [105] and thiobarbituric acid reactive substances [103,106] were found to be higher among people with Sz and carbonyl stress was found to be lower in people with the disorder [104,105,107] . However, those oxidative markers have overlapping levels between people with Sz and healthy individuals, suggesting the discriminability of those markers is low [102] .…”

“…One group suggested that only a subgroup of study participants with the glyoxalase Ⅰ (GLO1) deficits showed distinct patterns of oxidative stress abnormality in the plasma [104] , suggesting GLO1 deficits and oxidative stress may contribute to development of a certain subtype of Sz. However, evidence also suggests these oxidative markers show dynamic nonlinear changes during hospitalization and levels could be associated with the dosage of antipsychotics irrespective of the treatment responses [107] . If this finding is replicated, the utility of these markers may be restricted to determining medication compliance.…”

Pathophysiology of Patients with Schizophrenia: Genetic and Environmental Factors

“…In 2010, a cross-sectional study of chronic schizophrenia reported altered peripheral carbonyl stress markers, including high levels of serum pentosidine that accumulates following carbonyl stress and low levels of pyridoxal (vitamin B6) that detoxifies reactive carbonyl compounds 30) . In crosssectional and longitudinal studies, we investigated if the serum levels of these markers reflected the clinical course of the disorder 31) . One hundred and thirty-seven acute-stage Japanese patients were enrolled.…”

Biomarkers and schizophrenia: a qualitative review

“…Converging evidence indicates that the OS plays a role in SCZ pathophysiology [46][47][48][49]. A study on the disturbances in antioxidative defense systems indicated an increase in free radical generation and antioxidant defense impairment in SCZ patients [46].…”

“…Accumulation of these products is called carbonyl stress, and has been suggested as an environmental factor in the pathophysiology of SCZ [47,49,53]. AGEs interact with AGE receptors (RAGE) on the cell membrane, which induces deleterious effects by increasing oxidative and carbonyl stress [49,54].…”