Enhanced carbonyl stress and disrupted white matter integrity in schizophrenia

Carbonyl stress is a state caused by an increase in rich reactive carbonyl compounds (RCOs); RCOs facilitate the formation of advanced glycation end products (AGEs), which are associated with various age-related illnesses. Recently, enhanced carbonyl stress and lower levels of pyridoxal, a kind of vitamin B6 that scavenges RCOs, have been shown to be associated with schizophrenia. Meanwhile, lower levels of pyridoxal have been reported to decrease myelination through the biochemical process of carbonyl stress. Despite a number of reports on white matter disruption in schizophrenia, it is unclear whether this disruption is related to enhanced carbonyl stress. Therefore, we investigated the relationship between carbonyl stress and white matter integrity in schizophrenia using diffusion tensor imaging. A total of 53 patients with schizophrenia and 83 age- and gender-matched healthy controls were recruited. We used plasma pentosidine, an AGE, and serum pyridoxal as carbonyl stress markers. Between-group differences in these carbonyl stress markers and their relationships with white matter integrity were investigated using Tract-Based Spatial Statistics. In the schizophrenia group, plasma pentosidine level was significantly higher and serum pyridoxal level was lower than those of controls. There was a significant negative correlation between plasma pentosidine and white matter integrity in the schizophrenia group, but not in the control group. Our findings suggest that enhanced carbonyl stress is a possible underlying mechanism of white matter microstructural disruption in schizophrenia.