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White matter microstructure alterations in early psychosis and schizophrenia
Tommaso Pavan1, Yasser Alemán-Gómez2, Raoul Jenni3
1Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. tommaso.pavan@chuv.ch.
Abstract:
Studies on schizophrenia feature diffusion magnetic resonance imaging (dMRI) to investigate white matter (WM) anomalies. The heterogeneity in the possible interpretations of typical Diffusion Tensor Imaging (DTI) metrics highlights the importance of increasing their specificity. Here, we characterize WM pathology in early psychosis (EP) and schizophrenia (SZ) with increased specificity using advanced dMRI: Diffusion Kurtosis Imaging and the biophysical model White Matter Tract Integrity - Watson (WMTI-W). This enables us to better characterize WM abnormalities, while preserving good sensitivity to group differences, and relate them to the current literature (ENIGMA-schizophrenia), patient's clinical characteristics and symptomatology. dMRI-derived microstructure features were extracted from all of WM and from individual regions of interest in 275 individuals. 93 subjects diagnosed with EP and 47 with SZ were compared respectively to 135 age-range matched healthy controls (HC). WM DTI diffusivities were higher, while kurtosis was lower in EP vs HC and in SZ vs HC. Differences were more widespread in EP than SZ. The regional alterations found in our cohort matched the DTI patterns found in ENIGMA-schizophrenia. WMTI-W model parameters indicate that the WM alterations in patients come primarily from the extra-axonal compartment, consistent with abnormal myelin integrity in the disease pathology. The direct link between WM alterations and symptomatology is, however, limited.
Insights
Advanced diffusion MRI reveals white matter (WM) abnormalities in early psychosis and schizophrenia, primarily linked to myelin integrity. These findings offer higher specificity for characterizing WM pathology in these conditions.
Area of Science:
- Neuroimaging
- Psychiatry
- Biophysics
Background:
- Schizophrenia research frequently uses diffusion magnetic resonance imaging (dMRI) to study white matter (WM) anomalies.
- Typical Diffusion Tensor Imaging (DTI) metrics have interpretation heterogeneity, necessitating increased specificity.
- Advanced dMRI techniques can provide more detailed insights into WM pathology.
Purpose of the Study:
- To characterize WM pathology in early psychosis (EP) and schizophrenia (SZ) with enhanced specificity using advanced dMRI.
- To compare WM microstructure features between EP, SZ, and healthy controls (HC).
- To relate WM alterations to existing literature (ENIGMA-schizophrenia) and clinical characteristics.
Main Methods:
- Employed advanced dMRI techniques: Diffusion Kurtosis Imaging and the White Matter Tract Integrity - Watson (WMTI-W) biophysical model.
- Extracted dMRI-derived microstructure features from WM in 275 individuals (93 EP, 47 SZ, 135 HC).
- Compared WM DTI diffusivities and kurtosis, and WMTI-W model parameters between patient groups and HC.
Main Results:
- Higher WM DTI diffusivities and lower kurtosis were observed in EP and SZ compared to HC.
- WM alterations were more widespread in early psychosis than in schizophrenia.
- WMTI-W model parameters suggested alterations originate mainly from the extra-axonal compartment, indicating potential myelin integrity issues.
- Regional alterations aligned with patterns from the ENIGMA-schizophrenia cohort.
- A limited direct link was found between WM alterations and patient symptomatology.
Conclusions:
- Advanced dMRI, including Diffusion Kurtosis Imaging and WMTI-W, provides specific characterization of WM pathology in EP and SZ.
- Findings suggest abnormal myelin integrity as a key component of WM alterations in these conditions.
- While WM abnormalities are evident, their direct correlation with current symptomatology requires further investigation.
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