Dataset Information

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment.

ABSTRACT:

Background

Schizophrenia is associated with progressive white matter changes, but it is unclear whether antipsychotic medications contribute to these. Our objective was to characterize effects of short-term treatment with risperidone on white matter diffusion indices.

Methods

We recruited 42 patients with schizophrenia (30 never treated and 12 currently untreated) and 42 matched healthy control subjects in this prospective case-control neuroimaging study. Patients received a 6-week trial of risperidone. Using diffusion tensor imaging, we assessed microstructural (fractional anisotropy, mean diffusivity, and radial diffusivity) and macrostructural (radial fiber trophy) white matter integrity deficits in unmedicated patients compared with control subjects and change in white matter integrity in patients before and after antipsychotic treatment (mean risperidone dose at end point was 3.73 ± 1.72 mg).

Results

At baseline, fractional anisotropy was decreased in the left medial temporal white matter (cluster extent: 123 voxels; Montreal Neurological Institute peak coordinates: x = -51, y = -44, z = -7; α < .05), and mean diffusivity was increased in the fusiform/lingual gyrus white matter extending to the hippocampal part of the cingulum (cluster extent: 185 voxels; peak coordinates: x = -27, y = -49, z = 2; α < .04) in patients compared with control subjects. Radial diffusivity and macrostructure were not abnormal. None of the diffusion indices showed a significant change after 6 weeks of treatment with both voxelwise and whole-brain white matter analyses.

Conclusions

We demonstrate microstructural white matter integrity abnormalities in the absence of macrostructural impairment in unmedicated patients with primarily early-stage schizophrenia. In our data, we found no significant white matter changes after short-term treatment with risperidone.

SUBMITTER: Kraguljac NV

PROVIDER: S-EPMC6500745 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment.

Kraguljac Nina Vanessa NV Anthony Thomas T Skidmore Frank Michael FM Marstrander Jon J Morgan Charity Johanna CJ Reid Meredith Amanda MA White David Matthew DM Jindal Ripu Daman RD Melas Skefos Nicholas Harry NH Lahti Adrienne Carol AC

Biological psychiatry. Cognitive neuroscience and neuroimaging 20190123 5

<h4>Background</h4>Schizophrenia is associated with progressive white matter changes, but it is unclear whether antipsychotic medications contribute to these. Our objective was to characterize effects of short-term treatment with risperidone on white matter diffusion indices.<h4>Methods</h4>We recruited 42 patients with schizophrenia (30 never treated and 12 currently untreated) and 42 matched healthy control subjects in this prospective case-control neuroimaging study. Patients received a 6-wee ...[more]

PMID: 30852126

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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

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment.

Background

Methods

Results

Conclusions

Publications

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment.

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