title: Microglial activation and progressive brain changes in schizophrenia.
abstract: Schizophrenia is a debilitating disorder that typically begins in adolescence and is characterized by perceptual abnormalities, delusions, cognitive and behavioural disturbances and functional impairments. While current treatments can be effective, they are often insufficient to alleviate the full range of symptoms. Schizophrenia is associated with structural brain abnormalities including grey and white matter volume loss and impaired connectivity. Recent findings suggest these abnormalities follow a neuroprogressive course in the earliest stages of the illness, which may be associated with episodes of acute relapse. Neuroinflammation has been proposed as a potential mechanism underlying these brain changes, with evidence of increased density and activation of microglia, immune cells resident in the brain, at various stages of the illness. We review evidence for microglial dysfunction in schizophrenia from both neuroimaging and neuropathological data, with a specific focus on studies examining microglial activation in relation to the pathology of grey and white matter. The studies available indicate that the link between microglial dysfunction and brain change in schizophrenia remains an intriguing hypothesis worthy of further examination. Future studies in schizophrenia should: (i) use multimodal imaging to clarify this association by mapping brain changes longitudinally across illness stages in relation to microglial activation; (ii) clarify the nature of microglial dysfunction with markers specific to activation states and phenotypes; (iii) examine the role of microglia and neurons with reference to their overlapping roles in neuroinflammatory pathways; and (iv) examine the impact of novel immunomodulatory treatments on brain structure in schizophrenia.
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.|Centre for Neural Engineering, The University of Melbourne, Carlton, VIC, Australia.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: L E
authors.identifier: http://orcid.org/0000-0001-8258-8925
authors.initials: LE
authors.lastname: Laskaris
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: M A
authors.identifier: http://orcid.org/0000-0002-7100-651X
authors.initials: MA
authors.lastname: Di Biase
authors.affiliation: Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.|Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia.
authors.forename: I
authors.identifier: http://orcid.org/0000-0003-3957-3861
authors.initials: I
authors.lastname: Everall
authors.affiliation: Centre for Neural Engineering, The University of Melbourne, Carlton, VIC, Australia.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: G
authors.identifier: http://orcid.org/0000-0002-1096-1986
authors.initials: G
authors.lastname: Chana
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Christopoulos
authors.affiliation: Centre for Neural Engineering, The University of Melbourne, Carlton, VIC, Australia.|Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia.
authors.forename: E
authors.identifier: http://orcid.org/0000-0003-4263-9972
authors.initials: E
authors.lastname: Skafidas
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: V L
authors.initials: VL
authors.lastname: Cropley
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.|Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.|Florey Institute for Neurosciences and Mental Health, Parkville, VIC, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Pantelis
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D017628:Microglia / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology