Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia

Title: Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia
Authors: Liu, Z
Zhang, J
Zhang, K
Zhang, J
Li, X
Cheng, W
Li, M
Zhao, L
Deng, W
Guo, W
Ma, X
Wang, Q
Matthews, PM
Feng, J
Li, T
Item Type: Journal Article
Abstract: Disease association studies have characterized altered resting-state functional connectivities describing schizophrenia, but failed to model symptom expression well. We developed a model that could account for symptom severity and meanwhile relate this to disease-related functional pathology. We correlated BOLD signal across brain regions and tested separately for associations with disease (disease edges) and with symptom severity (symptom edges) in a prediction-based scheme. We then integrated them in an "edge bi-color" graph, and adopted mediation analysis to test for causality between the disease and symptom networks and symptom scores. For first-episode schizophrenics (FES, 161 drug-naïve patients and 150 controls), the disease network (with inferior frontal gyrus being the hub) and the symptom-network (posterior occipital-parietal cortex being the hub) were found to overlap in the temporal lobe. For chronic schizophrenis (CS, 69 medicated patients and 62 controls), disease network was dominated by thalamocortical connectivities, and overlapped with symptom network in the middle frontal gyrus. We found that symptom network mediates the relationship between disease network and symptom scores in FEP, but was unable to define a relationship between them for the smaller CS population. Our results suggest that the disease network distinguishing core functional pathology in resting-state brain may be responsible for symptom expression in FES through a wider brain network associated with core symptoms. We hypothesize that top-down control from heteromodal prefrontal cortex to posterior transmodal cortex contributes to positive symptoms of schizophrenia. Our work also suggests differences in mechanisms of symptom expression between FES and CS, highlighting a need to distinguish between these groups.
Issue Date: 1-Sep-2018
Date of Acceptance: 6-Apr-2018
URI: http://hdl.handle.net/10044/1/60827
DOI: https://doi.org/10.1002/hbm.24190
ISSN: 1065-9471
Publisher: Wiley
Start Page: 3503
End Page: 3515
Journal / Book Title: Human Brain Mapping
Volume: 39
Issue: 9
Copyright Statement: © 2018 Owner. This is the accepted version of the following article: Liu, Z, Zhang, J, Zhang, K, et al. Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia. Hum Brain Mapp. 2018; 39: 3503– 3515. https://doi.org/10.1002/hbm.24190, which has been published in final form at https://doi.org/10.1002/hbm.24190.
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neuroimaging
Radiology, Nuclear Medicine & Medical Imaging
Neurosciences & Neurology
disease association study
functional brain network
resting-state fMRI
schizophrenia
symptom association study
STATE FUNCTIONAL CONNECTIVITY
FINAL COMMON PATHWAY
MCI CLASSIFICATION
GLOBAL SIGNAL
HALLUCINATIONS
DISORDERS
MRI
REGIONS
ANXIETY
SENSE
disease association study
functional brain network
resting-state fMRI
schizophrenia
symptom association study
disease association study
functional brain network
resting-state fMRI
schizophrenia
symptom association study
1109 Neurosciences
1702 Cognitive Sciences
Experimental Psychology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-04-24
Appears in Collections:Department of Medicine
Faculty of Medicine



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