Dialogues of delivery: a multilingual question-answer dataset for maternal healthcare in East African languages.

Psychotic disorders, including schizophrenia (SZ), pose considerable challenges for the affected individuals, their families, and the broader community []. Recent research highlights the key role of white matter (WM) in this disease, reporting global structural changes across the brain of people suffering from psychosis [, ]. Thanks to its ability to exploit the random motion of water molecules, diffusion MRI (dMRI) allows us to explore the cellular environment and infer the microstructural properties of the underlying biological tissue in vivo []. In participants with psychosis, Diffusion Tensor Imaging (DTI) studies of WM consistently reported patterns of reduced fractional anisotropy (FA) and increased mean diffusivity (MD) [, , ]. These WM alterations are considered global, affecting the entire WM to varying degrees depending on the region [], most notably in the frontal and prefrontal areas [, ]. One of the largest meta-analyses of schizophrenia patients vs controls reported the highest effect size in dMRI metrics for the average brain FA ( = 0.42), followed by the FA in the anterior corona radiata, and the genu and body of the corpus callosum []. In our recent work [], we reproduced these high effect sizes in the same brain regions in patients with early psychosis (EP) and SZ. Additionally, we reported a decrease in Diffusion Kurtosis Imaging metrics [] in both clinical groups as compared to age range-matched controls, and identified specific microstructure patterns of alterations using the biophysical diffusion model, White Matter Tract Integrity - Watson [] (WMTI-W). Specifically, DKI provides complementary information about tissue heterogeneity by going beyond the Gaussian DTI approximation. DKI has been able to detect widespread WM abnormality in regions where typical DTI metrics (FA, MD) did not [], e.g. regions with complex fibre arrangement [], subtle abnormalities in subjects at high risk for psychosis [] and microstructural connectivity patterns associated with processing speed deficits in SZ []. WMTI-W enables the estimation of compartment specific (intra- and extra-axonal) properties that are excellent proxies for intra-axonal injury, inflammation and abnormal myelin integrity [–]. WMTI-W improves upon more commonly found models like Free-water elimination [] (FWE), by enabling the estimation of specific microstructural features, such as axonal density () and compartment-specific diffusivities, with fewer ad hoc assumptions and fit constraints [, ], resulting in increased validity []. For an overview of the effect of various pathological processes on DTI, DKI and WMTI-W diffusion metrics, see references [, ]. Thanks to the advanced dMRI techniques, in our previous work we found that WM alterations manifested predominantly in the extra-axonal space, as a significant increase in extra-axonal diffusivities, and that they were already present at the EP stage []. This latter finding is consistent with the literature showing that WM changes have been observed before the onset of psychosis [, ]. In ultra-high-risk individuals, existing WM alterations do not appear to suddenly worsen with the onset of psychosis []. Instead, longitudinal studies show a prematurely arrested FA increase during development [], and a progressive reduction in WM FA in those who transitioned []. Moreover, these alterations were not associated with symptomatology [, ]. Various mechanisms have been proposed to explain WM alterations, ranging from early aberrant axonal pruning [] and neuroplasticity [], to redox dysregulation [], and glutamatergic dysfunctions [, ]. A growing number of studies included neuroinflammation [–] and changes in neuroglia [, ] in the aetiology of psychosis. studies reported a decrease in astrocytes [] and oligodendrocytes [], which were estimated to be 20 to 27% lower in SZ patients than controls [, ]. On the other hand, in those patients who had high expression of inflammatory markers, ~40-50% of the brains exhibited increased immune activation (as measured by interleukin-6) in the dorsolateral prefrontal (PFC) and orbitofrontal cortices [], increased astrogliosis [] and reduced grey matter volume []. In-vivo dMRI studies have reported links between WM alterations (FW, free-water imaging [], i.e., reduced tissue compartment) and increased blood inflammatory cytokines [].