Abstract
Biomarkers are still missing for schizophrenia. An objective measure of disease extend or severity would greatly improve the stratification of patients which is an important step for the research, development and administration of stage specific treatments. During the past years, the development of brain imaging has allowed to highlight that abnormalities of white matter diffusion properties can be detected early in the time course of the disease and are rapidly widespread, involving all cerebral lobes. In parallel, a growing number of animal studies suggested that redox dysregulation and more specifically a deficiency in brain glutathione (GSH), could lead to oligodendrocyte impairment, alterations of white matter integrity and eventually to the development of schizophrenia.
Here, we propose that peripheral markers of oxidative stress can predict the level of cerebral white matter anomalies in early psychosis patients. Precisely, we first suggest that blood levels of the main cerebral anti-oxidant, namely GSH, but also levels of its related enzymes (i.e glutathione peroxidase (GPx) and glutathione reductase (GR)) and precursors (i.e. cysteine and cysteine) will be reduced in early psychosis patients when compared to healthy controls. Secondly, we anticipate that GSH, GPx, GR, cysteine and cysteine blood levels will be well correlated with generalized fractional anisotropy (gFA) - a proxy for cerebral white matter integrity - computed from magnetic resonance imaging (MRI) diffusion brain scans of early psychosis patients.
We selected a subgroup of 49 psychotic patients for which we had blood and MRI data from the full sample of the TIPP (Treatment and early Intervention in Psychosis Program) and chronic schizophrenia cohort. 64 age and sex matched healthy controls were also recruited for a total of 113 participants aged between 18 and 35 years old.
Independent t-tests were performed to compare average gFA, cysteine, cystine, GPx, Gr and GSH levels between patients and healthy control groups. We also tested the correlations between average gFA values and blood marker values (i.e., cysteine, cystine, GPx, Gr, and GSH) in the two groups independently.
We first observed that cerebral white matter integrity estimated using average gFA was reduced in early psychosis patients when compared to healthy controls. Second, the activity levels of GPx, the enzyme responsible for the elimination of peroxides were lower in patients than in controls. In contrast, GSH and its precursors cystine and cysteine were higher in the group of patients. Third, we reported that GSH levels were positively correlated with gFA in healthy controls and that cysteine levels could predict the level of cerebral white matter anomalies in early psychosis patients.
Although further exploration is needed to better understand the precise relationships between peripheral blood antioxidants and alterations of brain anatomy, peripheral cysteine levels could represent a quick and economic way to stratify patients and assess the extent of their cerebral alterations.