Local-to-remote cortical connectivity in early- and adulthood-onset schizophrenia.

L Jiang,H-J Li,X-N Zuo,Y Xu,X-T Zhu,Z Yang

doi:10.1038/tp.2015.59

Abstract

Schizophrenia is increasingly thought of as a brain network or connectome disorder and is associated with neurodevelopmental processes. Previous studies have suggested the important role of anatomical distance in developing a connectome with optimized performance regarding both the cost and efficiency of information processing. Distance-related disturbances during development have not been investigated in schizophrenia. To test the distance-related miswiring profiles of connectomes in schizophrenia, we acquired resting-state images from 20 adulthood-onset (AOS) and 26 early-onset schizophrenia (EOS) patients, as well as age-matched healthy controls. All patients were drug naive and had experienced their first psychotic episode. A novel threshold-free surface-based analytic framework was developed to examine local-to-remote functional connectivity profiles in both AOS and EOS patients. We observed consistent increases of local connectivity across both EOS and AOS patients in the right superior frontal gyrus, where the connectivity strength was correlated with a positive syndrome score in AOS patients. In contrast, EOS but not AOS patients exhibited reduced local connectivity within the right postcentral gyrus and the left middle occipital cortex. These regions' remote connectivity with their interhemispheric areas and brain network hubs was altered. Diagnosis–age interactions were detectable for both local and remote connectivity profiles. The functional covariance between local and remote homotopic connectivity was present in typically developing controls, but was absent in EOS patients. These findings suggest that a distance-dependent miswiring pattern may be one of the key neurodevelopmental features of the abnormal connectome organization in schizophrenia.

Highlights

Schizophrenia is a severe psychiatric disease associated with a series of mental impairments including hallucinations, delusions, loss of initiative and cognitive dysfunction
Distance-related disturbances of functional connectivity have been reported in schizophrenia across different age groups,[24,25] most resting-state functional magnetic resonance imaging-based findings in schizophrenia have presented large discrepancies,[26,27,28] which may partly reflect the grand challenges of human brain functional connectomics at the current stage
Functional covariance between local connectivity and remote connectivity For each cluster showing significant changes of both local and remote functional connectivity in Early-onset schizophrenia (EOS) or AOS patients, we examined the relationship between its local short-range connectivity and remote long-range connectivity by computing the Pearson’s correlation coefficient between the average 2dReHo and the average Fisher z-value of the functional connectivity within

Summary

Introduction

Schizophrenia is a severe psychiatric disease associated with a series of mental impairments including hallucinations, delusions, loss of initiative and cognitive dysfunction. The widely distributed clinical symptoms have been increasingly hypothesized to be attributed to the abnormal brain networks in schizophrenia This dysconnectivity hypothesis has been demonstrated by recent brain imaging studies,[1,2,3,4] which greatly advanced the elucidation of the pathological mechanism of schizophrenia. Another reemerged hypothesis is that the connectivity disruptions may reflect miswiring processes during brain development.[5,6,7,8]. Abnormal growth profiles of the structural features have been depicted recently and implied that this psychiatric condition may be associated with the abnormal maturational trajectories.[18,19,20] The anatomical distance has been identified as a key factor in developing a brain connectome with optimized performance regarding both the cost and efficiency of information processing, and short-range connections are selectively matured into long-range connections during the normal brain development.[21,22,23] distance-related disturbances of functional connectivity have been reported in schizophrenia across different age groups,[24,25] most resting-state functional magnetic resonance imaging (rfMRI)-based findings in schizophrenia have presented large discrepancies,[26,27,28] which may partly reflect the grand challenges of human brain functional connectomics at the current stage

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Results

Discussion

Conclusion