There is increasing evidence that blood oxygenation level-dependent signaling in white matter (WM) reflects WM functional activity. Whether this activity is altered in schizophrenia remains uncertain, as does whether it is related to established alterations of gray matter (GM) or the microstructure of WM tracts.

A total of 153 antipsychotic-naïve schizophrenia patients and 153 healthy comparison subjects were assessed by resting-state functional magnetic resonance imaging, diffusion tensor imaging, and high-resolution T1-weighted imaging. We tested for case–control differences in the functional activity of WM, and examined their relation to the functional activity of GM and WM microstructure. The relations between fractional anisotropy (FA) in WM and GM–WM functional synchrony were investigated as well. Then, we examined the associations of identified abnormalities to age, duration of untreated psychosis (DUP), and symptom severity.

Schizophrenia patients displayed reductions of the amplitude of low-frequency fluctuations (ALFF), GM–WM functional synchrony, and FA in widespread regions. Specifically, the genu of corpus callosum not only had weakening in the synchrony of functional activity but also had reduced ALFF and FA. Positive associations were found between FA and functional synchrony in the genu of corpus callosum as well. No significant association was found between identified abnormalities and DUP, and symptom severity.

The widespread weakening in the synchrony of functional activity of GM and WM provided novel evidence for functional alterations in schizophrenia. Regarding the WM function as a component of brain systems and investigating its alternation represent a promising direction for future research.

There is an appreciable overlap in the clinical presentation, epidemiology and treatment response of the two major psychotic disorders – schizophrenia and bipolar disorder. Nevertheless, the shared neurobiological correlates of these two disorders are still elusive. Using diffusion tensor imaging (DTI), we sought to identify brain regions which share altered white-matter connectivity across a clinical spectrum of psychotic disorders.

A sample of 41 healthy controls, 62 patients in a clinically stable state of an established psychotic disorder (40 with schizophrenia, 22 with bipolar disorder) were studied using DTI. Tract-based spatial statistics (TBSS) was used in order to study group differences between patients with psychosis and healthy controls using fractional anisotropy (FA). Probabilistic tractography was used in order to visualize the clusters that showed significant differences between these two groups.

The TBSS analysis revealed five clusters (callosal, posterior thalamic/optic, paralimbic, fronto-occipital) with reduced FA in psychosis. This reduction in FA was associated with an increase in radial diffusivity and a decrease in mode of anisotropy. Factor analysis revealed a single white-matter integrity factor that predicted social and occupational functioning scores in patients irrespective of the diagnostic categorization.

Our results show that a shared white-matter dysconnectivity links the two major psychotic disorders. These microstructural abnormalities predict functional outcome better than symptom-based diagnostic boundaries during a clinically stable phase of illness, highlighting the importance of seeking shared neurobiological factors that underlie the clinical spectrum of psychosis.