Abstract
Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.
Highlights
Onset schizophrenia (EOS) defined as schizophrenia beginning before the 18 years of age is more severe and less effected by environment and medication compared with late onset schizophrenia, which provides unique opportunity to explore pathophysiological mechanisms of schizophrenia (Kyriakopoulos et al, 2008; Yang et al, 2014)
We did not find the significant differences in whole brain gray matter volume (GMV) (p = 0.071) and mean frame-wise displacement (FD) (p = 0.17) between early onset schizophrenia (EOS) and healthy controls (HCs)
Compared with HCs, significantly reduced GMV were found in the bilateral cerebellum, temporal, orbitofrontal cortex (OFC), occipital, parietal, limbic lobes, hippocampus, insula, sensorimotor areas, cingulate cortex and precuneus in EOS (p < 0.05, FDR corrected; minimum cluster size of 50 voxels, Fig. 1)
Summary
Onset schizophrenia (EOS) defined as schizophrenia beginning before the 18 years of age is more severe and less effected by environment and medication compared with late onset schizophrenia, which provides unique opportunity to explore pathophysiological mechanisms of schizophrenia (Kyriakopoulos et al, 2008; Yang et al, 2014). Abnormal brain structural alterations have been widely reported in EOS (Douaud et al, 2009; Epstein et al, 2014). Reduced gray matter volume (GMV) in EOS, and even in ultra-high risk of psychosis individuals has been reported, the reduction in the latter is less obvious than that in schizophrenia (Douaud et al, 2007; Nenadic et al, 2015; Thompson et al, 2001). Reduced GMV in the high-order cortical areas were positively correlated to cognitive impairments and negatively correlated with psychiatric symptoms such as hallucination in schizophrenia The GMV abnormality might contribute to the underlying pathogenic mechanism of schizophrenia. To reveal the concurrent structural and functional changes, especially in functional integration may be an early biomarker for early diagnosis of EOS
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