The abnormal brain changes in patients with early-onset schizophrenia and the relationship with cognitive dysfunction : using multi-modal magnetic resonance imaging

Abstract

The relationships between the specific domains of cognitive functions, clinical symptoms, and social functioning in early-onset schizophrenia (EOS) have not been widely discussed. Few studies have investigated white matter abnormalities in EOS, and the relationship between abnormal white matter changes and cognitive manifestations in EOS is unclear. Besides, previous EOS studies often focused on a single gray matter feature, whereas independent measurements of gray matter volume, cortical thickness, and surface area could yield more information about the underlying disease mechanisms of EOS. In the first study, 36 patients with EOS and 36 age- and gender-matched healthy controls (HC) were recruited to this study. Best subsets regression was used to predict the best model for social functioning from the performance in specific neurocognitive tests and the clinical symptoms in EOS. In the second study, we used the whole-brain Tract-Based Spatial Statistics (TBSS) to analyze the white matter integrity between EOS and HC. At last, we performed the whole-brain Surface-Based Morphometric (SBM) assessment to decompose the gray matter volume into the cortical thickness and surface area, and to extract subcortical regional volumes. Group differences in fractional anisotropy, cortical volume, cortical thickness, surface area, and subcortical regional volumes were compared between EOS and HC. Moreover, the relationship between the abnormal brain structures and clinical or cognitive variables was investigated. The results showed that the best prediction model for social functioning in EOS included current positive and negative symptoms, and the performance in the logical memory test, digit span backward test, verbal fluency test, and visual pattern test (adjusted R2 = 0.47). Current positive and negative symptoms were negatively related to the SOFAS score, but delayed recall of logical memory and verbal fluency were positively associated with social functioning in EOS. The results of TBSS showed reductions of fractional anisotropy in the regions of genu and body of corpus callosum, bilateral anterior and superior corona radiata, left external capsule, and anterior limb of the internal capsule in EOS compared to HC. The SBM analysis showed the gray matter volume changes in the right supramarginal gyrus (SMG) were driven by increased surface area in EOS. Significant enlargements of bilateral lateral ventricle, caudate, pallidum, and right putamen were also reported in EOS compared to HC. In conclusion, widespread white matter abnormalities and subcortical volumetric alterations in EOS suggest EOS may share similarities and differences in the mechanism of disease with adult-onset schizophrenia. Abnormality in right SMG suggests that EOS may be more related to genetic factors. Targeted cognitive training related to verbal memory and verbal fluency may improve social functioning in patients with EOS.