Risk and resilience brain networks in treatment-resistant schizophrenia

Journal article


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 and Andrew Zalesky. (2018). Risk and resilience brain networks in treatment-resistant schizophrenia. Schizophrenia Research. 193, pp. 284-292. https://doi.org/10.1016/j.schres.2017.07.014
AuthorsEleni 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 and Andrew Zalesky
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.

Keywordsfunctional connectivity; schizophrenia; unaffected biological relatives; network efficiency; fMRI
Year2018
JournalSchizophrenia Research
Journal citation193, pp. 284-292
PublisherElsevier B.V.
ISSN0920-9964
Digital Object Identifier (DOI)https://doi.org/10.1016/j.schres.2017.07.014
Scopus EID2-s2.0-85025443602
Publisher's version
File Access Level
Controlled
Publication process dates
Deposited13 May 2021
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