White matter microstructure and the clinical risk for psychosis: A diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk

Background: Widespread white matter abnormalities are a frequent finding in chronic schizophrenia patients. More inconsistent results have been provided by the sparser literature on at-risk states for psychosis, i.e., emerging subclinical symptoms. However, considering risk as a homogenous construct, an approach of earlier studies, may impede our understanding of neuro-progression into psychosis.Methods: An analysis was conducted of 3-Tesla MRI diffusion and symptom data from 112 individuals (mean age, 21.97 +/- 4.19) within two at-risk paradigm subtypes, only basic symptoms (n = 43) and ultra-high risk (n = 37), and controls (n = 32). Between-group comparisons (involving three study groups and further split based on the subsequent transition to schizophrenia) of four diffusion-tensor-imaging-derived scalars were performed using voxelwise tract-based spatial statistics, followed by correlational analyses with Structured Interview for Prodromal Syndromes responses.Results: Relative to controls, fractional anisotropy was lower in the splenium of the corpus callosum of ultra-highrisk individuals, but only before stringent multiple-testing correction, and negatively correlated with General Symptom severity among at-risk individuals. At-risk participants who transitioned to schizophrenia within 3 years, compared to those that did not transition, had more severe WM differences in fractional anisotropy and radial diffusivity (particularly in the corpus callosum, anterior corona radiata, and motor/sensory tracts), which were even more extensive compared to healthy controls.Conclusions: These findings align with the subclinical symptom presentation and more extensive disruptions in converters, suggestive of severity-related demyelination or axonal pathology. Fine-grained but detectable differences among ultra-high-risk subjects (i.e., with brief limited intermittent and/or attenuated psychotic symptoms) point to the splenium as a discrete site of emerging psychopathology, while basic symptoms alone were not associated with altered fractional anisotropy.

Automated summary

The study compared white matter differences between individuals at risk for psychosis and controls using MRI diffusion and symptom data, revealing some correlations.