Structural impairment in superficial and deep white matter in schizophrenia.

OBJECTIVE: Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects. METHODS: We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman's rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing. RESULTS: Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial-occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing. CONCLUSION: We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

Association of clozapine with structural and resting-state functional abnormalities of the hippocampus in chronic schizophrenia.

Introduction: Abnormalities in the hippocampus have been extensively reported in schizophrenia research. However, inconsistent findings exist, and how structural and functional abnormalities of the hippocampus are associated with clinical symptoms in schizophrenia, especially concerning clozapine treatment, remains uncertain. Methods: We recruited 52 patients with schizophrenia, each with an illness duration of at least 5 years, and categorized them based on clozapine treatment. T1-weighted images and resting-state functional magnetic resonance imaging scans were obtained and analyzed to perform group comparisons of the structural and functional changes in the hippocampus. Volumes of the hippocampal subregions, as well as resting-state functional connectivity maps from these areas were compared between the groups. Associations with clinical symptoms, including the severity of psychiatric symptoms and cognitive functions, were investigated. Results: The clozapine group (n=23) exhibited smaller volumes in several hippocampal subregions, including the CA1, CA4, granule cell and molecular layers of the dentate gyrus, compared to the non-clozapine group (n=29). Seven clusters with significant group differences in functional connectivity with these hippocampal subregions were identified, with six of these clusters showing increased functional connectivity in the clozapine group. The reduced volumes of the hippocampal subregions were moderately associated with the severity of negative symptoms, general intelligence, and executive function. Discussion: Patients with schizophrenia undergoing clozapine treatment exhibited smaller volumes in the hippocampal subregions, which were moderately associated with negative symptoms and cognitive functions, compared to those without clozapine treatment.