Brain morphology is differentially impacted by peripheral cytokines in schizophrenia-spectrum disorder

Liliana Laskaris; Sam Mancuso; Cynthia Shannon Weickert; Andrew Zalesky; Gursharan Chana; Cassandra Wannan; Chad Bousman; Bernhard T Baune; Patrick McGorry; Christos Pantelis; Vanessa L Cropley

doi:10.1016/j.bbi.2021.04.002

Brain morphology is differentially impacted by peripheral cytokines in schizophrenia-spectrum disorder

Brain Behav Immun. 2021 Jul:95:299-309. doi: 10.1016/j.bbi.2021.04.002. Epub 2021 Apr 8.

Authors

Affiliations

¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia; Department of Psychiatry, The University of Melbourne, Australia. Electronic address: lily.laskaris@unimelb.edu.au.
² Department of Psychiatry, The University of Melbourne, Australia; Translational Clinical Psychology Research Unit, Institute for Social Neuroscience, Australia.
³ Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick NSW 2031, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA.
⁴ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia; Department of Biomedical Engineering, Melbourne School of Engineering, The University of Melbourne.
⁵ Department of Medicine, Royal Melbourne Hospital, Royal Parade, Melbourne, Australia.
⁶ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia; Department of Psychiatry, The University of Melbourne, Australia.
⁷ Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada.
⁸ Department of Psychiatry, The University of Melbourne, Australia; Department of Psychiatry, University of Münster, Germany; Florey Institute for Neurosciences and Mental Health, Parkville, VIC Australia.
⁹ Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia.
¹⁰ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia; Department of Psychiatry, The University of Melbourne, Australia; North Western Mental Health, Melbourne Health, Parkville, VIC Australia; Florey Institute for Neurosciences and Mental Health, Parkville, VIC Australia.
¹¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia; Department of Psychiatry, The University of Melbourne, Australia; Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia.

PMID: 33838248
DOI: 10.1016/j.bbi.2021.04.002

Abstract

Deficits in brain morphology are one of the most widely replicated neuropathological features in schizophrenia-spectrum disorder (SSD), although their biological underpinnings remain unclear. Despite the existence of hypotheses by which peripheral inflammation may impact brain structure, few studies have examined this relationship in SSD. This study aimed to establish the relationship between peripheral markers of inflammation and brain morphology and determine whether such relationships differed across healthy controls and individuals with first episode psychosis (FEP) and chronic schizophrenia. A panel of 13 pro- and anti-inflammatory cytokines were quantified from serum in 175 participants [n = 84 Healthy Controls (HC), n = 40 FEP, n = 51 Chronic SCZ]. We first performed a series of permutation tests to identify the cytokines most consistently associated with brain structural regions. Using moderation analysis, we then determined the extent to which individual variation in select cytokines, and their interaction with diagnostic status, predicted variation in brain structure. We found significant interactions between cytokine level and diagnosis on brain structure. Diagnostic status significantly moderated the relationship of IFNγ, IL4, IL5 and IL13 with frontal thickness, and of IFNγ and IL5 and total cortical volume. Specifically, frontal thickness was positively associated with IFNγ, IL4, IL5 and IL13 cytokine levels in the healthy control group, whereas pro-inflammatory cytokines IFNγ and IL5 were associated with lower total cortical volume in the FEP group. Our findings suggest that while there were no relationships detected in chronic schizophrenia, the relationship between peripheral inflammatory markers and select brain regions are differentially impacted in FEP and healthy controls. Longitudinal investigations are required to determine whether the relationship between brain structure and peripheral inflammation changes over time.

Keywords: Cytokines; Inflammation; MRI; Psychosis; Schizophrenia.

Publication types

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

MeSH terms

Brain / anatomy & histology*
Brain / diagnostic imaging
Cytokines*
Humans
Inflammation
Magnetic Resonance Imaging
Schizophrenia* / diagnostic imaging

Substances

Cytokines