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Pathology of white matter integrity in three major white matter fasciculi: A post-mortem study of schizophrenia and treatment status.

ABSTRACT: BACKGROUND AND PURPOSE:Imaging studies have shown that people with schizophrenia exhibit abnormal connectivity termed "dysconnectivity" in several white matter tracts, including the cingulum bundle (CB), corpus callosum (CC), and arcuate fasciculus (AF). This study aimed to elucidate potential contributors to schizophrenia "dysconnectivity." EXPERIMENTAL APPROACH:Western blot analysis was used to compare protein levels of myelin basic protein, neurofilament heavy, autophagosome marker LC3, and microtubule marker ?-tubulin in post-mortem human CB, CC, and AF in schizophrenia subjects (SZ) and matched normal controls (NC). Additionally, SZ cases were subdivided by treatment status: off-medication (OFF) or on-medication (ON). KEY RESULTS:In the CC, the combined SZ group exhibited less neurofilament heavy protein than the NCs. In the CB, the combined SZ group had similar levels of ?-tubulin protein versus NC, but OFF subjects had increased ?-tubulin protein versus ON and NCs. There were significant correlations between ?-tubulin and all other proteins but only in the CB. The strong negative relationship between ?-tubulin versus myelin basic protein and ?-tubulin versus LC3 in NCs was absent in SZs; coefficients comparison showed significant differences. Preliminary race analyses revealed that African American SZ had less AF ?-tubulin than Caucasian SZ and African American normal controls. CONCLUSIONS AND IMPLICATIONS:The results show a relationship between tract- and protein-specific abnormalities and diagnosis, treatment, and race. These data suggest there is a dysregulation of the relationship between ?-tubulin and the other markers of white matter integrity observed in the CB in schizophrenia.

SUBMITTER: Schoonover KE

PROVIDER: S-EPMC6451068 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Pathology of white matter integrity in three major white matter fasciculi: A post-mortem study of schizophrenia and treatment status.

Schoonover Kirsten E KE Farmer Charlene B CB Cash Andrew E AE Roberts Rosalinda C RC

British journal of pharmacology 20190318 8

<h4>Background and purpose</h4>Imaging studies have shown that people with schizophrenia exhibit abnormal connectivity termed "dysconnectivity" in several white matter tracts, including the cingulum bundle (CB), corpus callosum (CC), and arcuate fasciculus (AF). This study aimed to elucidate potential contributors to schizophrenia "dysconnectivity."<h4>Experimental approach</h4>Western blot analysis was used to compare protein levels of myelin basic protein, neurofilament heavy, autophagosome ma ...[more]

PMID: 30735241

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Project description: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.

Dataset Information

Pathology of white matter integrity in three major white matter fasciculi: A post-mortem study of schizophrenia and treatment status.

Publications

Pathology of white matter integrity in three major white matter fasciculi: A post-mortem study of schizophrenia and treatment status.

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