Abstract
Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). The diagnostic specificity remains unclear, with bipolar disorders (BD) frequently conceptualized as a less severe clinical manifestation along a psychotic spectrum. Further, the age-related dynamics and possible sex differences of WM abnormalities in SZ and BD are currently understudied. Using tract-based spatial statistics (TBSS) we compared DTI-based microstructural indices between SZ (n = 128), BD (n = 61), and HC (n = 293). We tested for age-by-group and sex-by-group interactions, computed effect sizes within different age-bins and within genders. TBSS revealed global reductions in fractional anisotropy (FA) and increases in radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body and splenium of the corpus callosum, and lower FA in SZ compared to BD in right inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus, and no significant differences between BD and HC. The results were not strongly dependent on age or sex. Despite lack of significant group-by-age interactions, a sliding-window approach supported widespread WM involvement in SZ with most profound differences in FA from the late 20 s.
Highlights
Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC)
We found significant and widespread main effects of group on fractional anisotropy (FA) and radial diffusivity (RD), including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, forceps major and inferior fronto-occipital fasciculus
Pairwise comparisons revealed widespread FA reductions and RD increases in SZ compared to HC, and FA reductions in SZ compared to bipolar disorders (BD)
Summary
Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). Pathophysiology and clinical manifestation, with higher symptom burden, poorer function and worse outcome in SZ26 Including both patients with SZ and BD in the same analysis is vital for probing common and distinct etiological mechanisms across the psychosis spectrum. The evidence of strong modulating effects of sex on WM abnormalities in severe mental disorders is lacking, sexual dimorphisms in brain biology and clinical expression warrant further studies on possible sex by diagnosis interactions on the human brain
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