Abstract
Background: Schizophrenia is characterized by the disruption of microstructural white matter (WM) integrity, while the pathogenesis remains unclear. Inflammation has been associated with the WM pathology in schizophrenia. Interleukin 10 (IL-10) has been proven to be related to schizophrenia in both animal and human models. The aim of this study was to explore whether peripheral IL-10 was associated with microstructural WM integrity in schizophrenia.Methods: A total of 47 patients with schizophrenia (SZ) and 49 healthy controls (HC) underwent diffusion tensor imaging and venous blood sampling. Tract-based spatial statistics was conducted to explore the differences in fractional anisotropy (FA), radial diffusivity (RD), mean diffusivity (MD), and axial diffusivity (AD) between patients and controls. A quantitative chemiluminescence assay was performed to measure peripheral IL-10 levels. General linear regression analysis using a stepwise method was applied to examine the relationship between peripheral IL-10 and diffusion measures.Results: Compared with the HC, peripheral IL-10 levels were higher and a significant reduction of FA and AD, and increase of RD and MD were observed in SZ (corrected p < 0.05). A regression analysis revealed that peripheral IL-10 was negatively correlated with FA in the right posterior thalamic radiation and left inferior fronto-occipital fasciculus, in SZ (β = -0.51, p = 0.01; β = -0.47, p = 0.02, respectively) but not in HC (β = -0.01, p = 0.95; β = -0.003, p = 0.98, respectively), and the differences in regression curves were significant (z = 2.50, p = 0.01; z = 2.37, p = 0.02, respectively). IL-10 was negatively connected with MD in the right parietal arcuate fasciculus (β = -0.40, p = 0.048) and body of the corpus callosum (β = -0.43, p = 0.03) in SZ, while not in HC. The magnitude of correlation in the patient and control group was different (z = 2.48, p = 0.01 and z = 2.61, p < 0.01, respectively). In addition, IL-10 was positively correlated with RD in the right parietal arcuate fasciculus in patients (β = 0.45, p = 0.04) but not in HC (β = 0.26, p = 0.94), but the correlation coefficients were not significant (z = 0.98, p = 0.32).Conclusion: Our findings demonstrated that elevated peripheral IL-10 levels were associated with the disruption of microstructural WM integrity in schizophrenia, supporting the notion that inflammation plays a regulatory role in the pathology of microstructural WM and is associated with schizophrenia.
Highlights
Schizophrenia is considered a disconnection disorder characterized by disrupted white matter (WM) integrity (Viher et al, 2016; Di Biase et al, 2017; Kelly et al, 2018)
A global increase in radial diffusivity (RD) was found in schizophrenia patients in the right sagittal stratum, left posterior corona radiata, bilateral anterior corona radiata, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculus and the left posterior thalamic radiation compared with the healthy controls
A widespread increase of mean diffusivity (MD) was found in schizophrenia patients compared to the controls, with effects in the corpus callosum, right superior corona radiata, right anterior corona radiata and the bilateral superior longitudinal fasciculus
Summary
Schizophrenia is considered a disconnection disorder characterized by disrupted white matter (WM) integrity (Viher et al, 2016; Di Biase et al, 2017; Kelly et al, 2018). The pathogenesis of disrupted WM integrity in schizophrenia remains unclear, neuroinflammation mediated by cytokines appears to be an important pathogenic mechanism (Frodl and Amico, 2014; Najjar and Pearlman, 2015). Evidence from genomic, blood, postmortem and neuroimaging studies indicates that inflammation plays an important role in the pathophysiological process of schizophrenia (Borovcanin et al, 2015; Najjar and Pearlman, 2015; Fond et al, 2016; Khandaker and Dantzer, 2016; Shivakumar et al, 2018; Xiu et al, 2018). Schizophrenia is characterized by the disruption of microstructural white matter (WM) integrity, while the pathogenesis remains unclear. The aim of this study was to explore whether peripheral IL-10 was associated with microstructural WM integrity in schizophrenia
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