Eleni P Ganella1, Cali F Bartholomeusz2, Caio Seguin3, Sarah Whittle3, Chad Bousman4, Christina Phassouliotis3, Ian Everall5, Christos Pantelis6, Andrew Zalesky7. 1. 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; The Cooperative Research Centre (CRC) for Mental Health, Victoria, Australia; North Western Mental Health, Melbourne Health, Parkville, Victoria, Australia. Electronic address: e.ganella@student.unimelb.edu.au. 2. 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. 3. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia. 4. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; The Cooperative Research Centre (CRC) for Mental Health, Victoria, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, Victoria, Australia; Swinburne University of Technology, Centre for Human Psychopharmacology, Hawthorne, Victoria, Australia; The University of Melbourne, Department of General Practice, Parkville, Victoria, Australia. 5. The Cooperative Research Centre (CRC) for Mental Health, Victoria, Australia; North Western Mental Health, Melbourne Health, Parkville, Victoria, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, Victoria, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, Victoria, Australia; Melbourne School of Engineering, The University of Melbourne, Parkville, Victoria, Australia. 6. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; The Cooperative Research Centre (CRC) for Mental Health, Victoria, Australia; North Western Mental Health, Melbourne Health, Parkville, Victoria, Australia; Florey Institute for Neurosciences and Mental Health, Parkville, Victoria, Australia; Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, Victoria, Australia; Melbourne School of Engineering, The University of Melbourne, Parkville, Victoria, Australia. 7. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia; Melbourne School of Engineering, The University of Melbourne, Parkville, Victoria, Australia.
Abstract
INTRODUCTION: Up to 20% of individuals with schizophrenia show minimal or no response to medication and are considered to have 'treatment-resistant' schizophrenia (TRS). Unlike early and established schizophrenia, few studies have investigated resting-state functional connectivity (rs-FC) in TRS. Here, we test for disruptions in FC and altered efficiency of functional brain networks in a well-characterized cohort of TRS patients. METHODS: Resting-state functional magnetic resonance imaging was used to investigate functional brain networks in 42 TRS participants prescribed clozapine (30 males, mean age=41.3(10)) and 42 healthy controls (24 males, mean age=38.4(10)). Graph analysis was used to characterize between-group differences in local and global efficiency of functional brain network organization as well as the strength of FC. RESULTS: Global brain FC was reduced in TRS patients (p=0.0001). Relative to controls, 3.4% of all functional connections showed reduced strength in TRS (p<0.001), predominantly involving fronto-temporal, fronto-occipital and temporo-occipital connections. Global efficiency was reduced in TRS (p=0.0015), whereas local efficiency was increased (p=0.0042). CONCLUSIONS: TRS is associated with widespread reductions in rs-FC and altered network topology. Increased local functional network efficiency coupled with decreased global efficiency suggests that hub-to-hub connections are preferentially affected in TRS. These findings further our understanding of the neurobiological impairments in TRS.
INTRODUCTION: Up to 20% of individuals with schizophrenia show minimal or no response to medication and are considered to have 'treatment-resistant' schizophrenia (TRS). Unlike early and established schizophrenia, few studies have investigated resting-state functional connectivity (rs-FC) in TRS. Here, we test for disruptions in FC and altered efficiency of functional brain networks in a well-characterized cohort of TRS patients. METHODS: Resting-state functional magnetic resonance imaging was used to investigate functional brain networks in 42 TRS participants prescribed clozapine (30 males, mean age=41.3(10)) and 42 healthy controls (24 males, mean age=38.4(10)). Graph analysis was used to characterize between-group differences in local and global efficiency of functional brain network organization as well as the strength of FC. RESULTS: Global brain FC was reduced in TRS patients (p=0.0001). Relative to controls, 3.4% of all functional connections showed reduced strength in TRS (p<0.001), predominantly involving fronto-temporal, fronto-occipital and temporo-occipital connections. Global efficiency was reduced in TRS (p=0.0015), whereas local efficiency was increased (p=0.0042). CONCLUSIONS: TRS is associated with widespread reductions in rs-FC and altered network topology. Increased local functional network efficiency coupled with decreased global efficiency suggests that hub-to-hub connections are preferentially affected in TRS. These findings further our understanding of the neurobiological impairments in TRS.
Authors: Mary-Anne B MacKay; John W Paylor; James T F Wong; Ian R Winship; Glen B Baker; Serdar M Dursun Journal: Front Psychiatry Date: 2018-10-30 Impact factor: 4.157