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Risk and resilience brain networks in treatment-resistant schizophrenia
Eleni P Ganella Caio Seguin Cali F Bartholomeusz Sarah Whittle Chad Bousman Cassandra M.J. Wannan Maria Angelique Di Biase Christina Phassouliotis I P Everall Christos Pantelis
Eleni P Ganella
Caio Seguin
Cali F Bartholomeusz
Sarah Whittle
Chad Bousman
Cassandra M.J. Wannan
Maria Angelique Di Biase
Christina Phassouliotis
I P Everall
Christos Pantelis
Abstract
Background
Genes, molecules and neural circuits that are associated with, or confer risk to developing schizophrenia have been studied and mapped. It is hypothesized that certain neural systems may counterbalance familial risk of schizophrenia, and thus confer resilience to developing the disorder. This study sought to identify resting-state functional brain connectivity (rs-FC) representing putative risk or resilience endophenotypes in schizophrenia.
Methods
Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 42 individuals with treatment resistant schizophrenia (TRS), 16 unaffected first-degree family members (UFM) and 42 healthy controls. Whole-brain rs-FC networks were mapped for each individual and analysed graph theoretically to identify network markers associated with schizophrenia risk or resilience.
Results
The ~ 900 functional connections showing between-group differences were operationalized as conferring: i) resilience, ii) risk, or iii) precipitating risk and/or illness effects. Approximately 95% of connections belonged to the latter two categories, with substantially fewer connections associated with resilience. Schizophrenia risk primarily involved reduced frontal and occipital rs-FC, with patients showing additional reduced frontal and temporal rs-FC. Functional brain networks were characterized by greater local efficiency in UFM, compared to TRS and controls.
Conclusions
TRS and UFM share frontal and occipital rs-FC deficits, representing a ‘risk’ endophenotype. Additional reductions in frontal and temporal rs-FC appear to be associated with risk that precipitates psychosis in vulnerable individuals, or may be due to other illness-related effects, such as medication. Functional brain networks are more topologically resilient in UFM compared to TRS, which may protect UFM from psychosis onset despite familial liability.
Keywords
functional connectivity, schizophrenia, unaffected biological relatives, network efficiency, fMRI
Date
2018
Type
Journal article
Journal
Schizophrenia Research
Book
Volume
193
Issue
Page Range
284-292
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled