White matter impairments in patients with schizophrenia: A multisite diffusion MRI study

Abstract

There is a lack of convincing and replicative findings regarding white matter abnormalities in schizophrenia. Several multisite diffusion magnetic resonance imaging (dMRI) studies have been conducted to increase statistical power and reveal subtle white matter changes. Data pooling methods are crucial in joint analysis to compensate for the use of different scanners and image acquisition parameters. A harmonization method using raw dMRI data was developed to overcome the limited generalizability of previous data pooling methods. We obtained dMRI data of 242 healthy controls and 190 patients with schizophrenia from four different study sites. After applying the harmonization method to the raw dMRI data, a two-tensor whole-brain tractography was performed, and diffusion measures were compared between the two groups. The correlation of fractional anisotropy (FA) with the positive and negative symptoms was evaluated, and the interaction effect of diagnosis-by-age, age-squared, and sex was examined. The following white matter tracts showed significant group differences in the FA: the right superior longitudinal fascicle (SLF), the left-to-right lateral orbitofrontal commissural tract, pars orbitalis (pOr-pOr) commissural tract, and pars triangularis (pTr-pTr) commissural tract. The FA of the right SLF and pTr-pTr commissural tract were significantly associated with the Positive and Negative Syndrome Scale (PANSS) positive and negative scores. No significant interaction effect was observed. These findings add to the evidence on structural brain abnormalities in schizophrenia and can aid in obtaining a better understanding of the biological foundations of schizophrenia.