Elucidation of shared and specific white matter findings underlying psychopathology clusters in schizophrenia.

Background: Schizophrenia is associated with diverse white matter (WM) brain abnormalities. In this study, we sought to examine the WM microstructural findings which underlie clinical psychopathology clusters in schizophrenia and hypothesized that these symptom clusters are associated with common and unique WM tracts.

Methods: Overall, 76 healthy controls (HC), and 148 patients with schizophrenia (SZ) were recruited and severity of symptomatology in schizophrenia was assessed using the Positive and Negative Syndrome Scale. WM fractional anisotropy (FA) values were extracted from their diffusion tensor images. Psychopathology clusters were first determined using factor analysis and the relationship between these symptom factors and FA values were then assessed with structural equation modelling, which included covariates such as age, sex, duration of illness and medications prescribed.

Results: Patients with schizophrenia had reduced FA in the genu of corpus callosum (gCC) compared to HC. A three-factor model, namely Positive, Negative, Disorganised factors, was determined as the best fit for the data. All three psychopathology factors were associated with decreased FA in the gCC and bilateral cingulate gyrus. Higher Negative factor scores were uniquely associated with decreased FA in the right sagittal striatum and right superior longitudinal fasciculus.

Conclusions: This study found shared and specific WM changes and their associations with specific symptom clusters, which potentially allows for monitoring of such white matter findings associated with clinical presentations in schizophrenia over treatment and illness course.