Biology subjects

Van Dyken, P. C.

Publications and source records attributed to Van Dyken, P. C..

4 recordsLinked to original sources

bioRxiv2024

Neurite Density and Free Water in the Gray and White Matter of Early Psychosis Patients

Diffusion weighted imaging has been frequently used to characterize the white matter in patients with schizophrenia, but the most commonly used model, diffusion tensor imaging (DTI), is not specific to the histological nature of microstructural changes. This is particularly true in the more complex grey matter tissue. Furthermore, DTI changes have not been consistently reported in early schizophrenia populations, but this does not exclude more subtle changes that may not affect the model fit. Recently developed biophysical models of diffusion, such as the neurite orientation dispersion and density imaging (NODDI) model, may overcome these issues by quantifying specific tissue subcompartments, capturing diffusion profiles characteristic of intra-neurite, extra-neurite, and free water space. We applied the NODDI model to early schizophrenia patients (n=54) and healthy controls (n=51) from the Human Connectome Project - Early Psychosis dataset, investigating both the grey and white matter. We observed a diffuse, increased free water fraction throughout the grey matter, especially in the left insula, though there were not notable changes in the white matter. The spatial variation in the grey matter free water was not fully explained by the partial volume effects from the cerebrospinal fluid, indicating a role for tissue edema. The role of vasogenic processes in early stages of psychosis that may precede white matter anomalies documented in later disease stages warrant further investigation.

neuroscience↗

bioRxiv2024

Stable White Matter Structure in the First Three Years after Psychosis Onset

BackgroundWhite matter alterations observed using diffusion weighted imaging have become a hallmark of chronic schizophrenia, but it is unclear when these changes arise over the course of the disease. Nearly all studies thus far have been cross-sectional, so despite their large sample sizes, they cannot determine if changes accumulate as a degenerative process, or if patients with pre-existing white matter damage are predisposed to more chronic forms of schizophrenia. MethodsWe examined 160 scans comprising two years of annual follow-up data from n=42 controls and n=28 schizophrenia patients recruited in the first two years since their diagnosis, totalling two to three scans per subject. We additionally examined six-month follow-up data obtained from an ultra-high field (7 Tesla) scanner (n=68 scans; n=19 first-episode schizophrenia patients; n=15 controls) as a validation dataset. A longitudinal model was used to compare the trajectory of diffusion tenor parameters between patients and controls. Positive and negative symptom scores were correlated with diffusion parameters using ROI- and clustering-based approaches. ResultsWe failed to observe any longitudinal differences in any diffusion tensor imaging parameters between patients and controls in either dataset. We did, however, observe consistent associations between white matter alterations and negative symptoms in both datasets. ConclusionsWhite matter does not appear susceptible to schizophrenia-linked degeneration in the early stages of disease, but pre-existing pathology may be linked to disease severity.

neuroscience↗

bioRxiv2023

Cortical Network Disruption is Minimal in Early Stages of Psychosis

1Background and HypothesisChronic schizophrenia is associated with white matter disruption and topological reorganization of cortical connectivity but the trajectory of these changes over the disease course are poorly understood. Current white matter studies in first-episode psychosis (FEP) patients using diffusion magnetic resonance imaging (dMRI) suggest such disruption may be detectable at the onset of psychosis, but specific results vary widely and few reports have contextualized their findings with direct comparison to chronic patients. Here, we test the hypothesis that structural changes are not a significant feature of early psychosis. Study DesignDiffusion and T1-weighted 7T MR scans were obtained from N=113 (61 FEP patients, 37 controls, 15 chronic patients) recruited from an established cohort in London, Ontario. Voxel- and network-based analyses were used to detect changes in diffusion microstructural parameters. Graph theory metrics were used to probe changes in the cortical network hierarchy and to assess the vulnerability of hub regions to disruption. Experiments were replicated with N=167 (111 patients, 56 controls) from the Human Connectome Project - Early Psychosis (HCP-EP) dataset. Study ResultsWidespread microstructural changes were found in chronic patients, but changes in FEP patients were minimal. Unlike chronic patients, no appreciable topological changes in the cortical network were observed in FEP patients. These results were replicated in the early psychosis patients of the HCP-EP datasets, which were indistinguishable from controls on nearly all metrics. ConclusionsThe white matter structural changes observed in chronic schizophrenia are not a prominent feature in the early stages of this illness.

neuroscience↗

bioRxiv2023

Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation.

Astrocytes are intimately linked with brain vessels, a relationship that is critical for neuronal health and function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. We characterized structural and transcriptional changes in mouse cortical astrocytes and microvessels during the first two postnatal weeks and found that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, was highly expressed in astrocytes at birth and then decreased rapidly. Astrocyte-selective ablation of Hmgb1 at birth affected astrocyte morphology and endfoot placement, altered distribution of endfoot proteins connexin43 and aquaporin-4, induced transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupted endothelial ultrastructure. While lack of astroglial Hmgb1 did not affect the blood-brain barrier or angiogenesis postnatally, it impaired neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as a key player in postnatal gliovascular maturation.

developmental biology↗