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 A Di Biase; Christina Phassouliotis; Ian Everall; Christos Pantelis; Andrew Zalesky

doi:10.1016/j.schres.2017.07.014

Risk and resilience brain networks in treatment-resistant schizophrenia

Schizophr Res. 2018 Mar:193:284-292. doi: 10.1016/j.schres.2017.07.014. Epub 2017 Jul 21.

Affiliations

¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia; The Centre for Youth Mental Health, The University of Melbourne, Victoria, Australia; The Cooperative Research Centre (CRC) for Mental Health, Australia. Electronic address: [email protected].
² Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
³ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia; The Centre for Youth Mental Health, The University of Melbourne, Victoria, Australia.
⁴ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; The Cooperative Research Centre (CRC) for Mental Health, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia; Swinburne University of Technology, Centre for Human Psychopharmacology, Hawthorne, VIC, Australia; The University of Melbourne, Department of General Practice, Parkville, VIC, Australia.
⁵ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Victoria, Australia; The Centre for Youth Mental Health, The University of Melbourne, Victoria, Australia; The Cooperative Research Centre (CRC) for Mental Health, Australia.
⁶ Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; The Cooperative Research Centre (CRC) for Mental Health, Australia; North Western Mental Health, Melbourne Health, Parkville, VIC, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, VIC, Australia.
⁷ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; The Cooperative Research Centre (CRC) for Mental Health, Australia; North Western Mental Health, Melbourne Health, Parkville, VIC, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, VIC, Australia.
⁸ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, VIC, Australia; Melbourne School of Engineering, The University of Melbourne, Parkville, VIC, Australia.

PMID: 28735641
DOI: 10.1016/j.schres.2017.07.014

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; Network efficiency; Schizophrenia; Unaffected biological relatives; fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antipsychotic Agents / adverse effects
Brain / diagnostic imaging
Brain / drug effects
Brain / physiopathology*
Brain Mapping*
Female
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Middle Aged
Models, Neurological
Nerve Net / diagnostic imaging
Nerve Net / drug effects
Nerve Net / physiopathology*
Neural Pathways / diagnostic imaging
Neural Pathways / physiopathology*
Oxygen / blood
Schizophrenia / diagnostic imaging
Schizophrenia / drug therapy
Schizophrenia / pathology*

Substances

Antipsychotic Agents
Oxygen