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Increased peripheral inflammation in schizophrenia is associated with worse cognitive performance and related cortical thickness reductions

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Abstract

While the biological substrates of brain and behavioural changes in persons with schizophrenia remain unclear, increasing evidence implicates that inflammation is involved. In schizophrenia, including first-episode psychosis and anti-psychotic naïve patients, there are numerous reports of increased peripheral inflammation, cognitive deficits and neuropathologies such as cortical thinning. Research defining the relationship between inflammation and schizophrenia symptomatology and neuropathology is needed. Therefore, we analysed the level of C-reactive protein (CRP), a peripheral inflammation marker, and its relationship with cognitive functioning in a cohort of 644 controls and 499 schizophrenia patients. In a subset of individuals who underwent MRI scanning (99 controls and 194 schizophrenia cases), we tested if serum CRP was associated with cortical thickness. CRP was significantly increased in schizophrenia patients compared to controls, co-varying for age, sex, overweight/obesity and diabetes (p < 0.006E-10). In schizophrenia, increased CRP was mildly associated with worse performance in attention, controlling for age, sex and education (R =− 0.15, p = 0.001). Further, increased CRP was associated with reduced cortical thickness in three regions related to attention: the caudal middle frontal, the pars opercularis and the posterior cingulate cortices, which remained significant after controlling for multiple comparisons (all p < 0.05). Together, these findings indicate that increased peripheral inflammation is associated with deficits in cognitive function and brain structure in schizophrenia, especially reduced attention and reduced cortical thickness in associated brain regions. Using CRP as a biomarker of peripheral inflammation in persons with schizophrenia may help to identify vulnerable patients and those that may benefit from adjunctive anti-inflammatory treatments.

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Data availability

The datasets from the current study are not publicly available due to ethics approval.

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Acknowledgements

This study was supported by the Australian Schizophrenia Research Bank (ASRB), which is supported by the National Health and Medical Research Council of Australia, the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute.

Funding

CSW is funded by the NSW Ministry of Health, Office of Health and Medical Research. CSW is a recipient of a National Health and Medical Research Council (Australia) Principal Research Fellowship (PRF) (#1117079). CSW is on an advisory board for Lundbeck, Australia Pty Ltd and in collaboration with Astellas Pharma Inc., Japan; however, neither of these are related to this study. VC was supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (1177370). CP was supported by a NHMRC Senior Principal Research Fellowship (1105825).

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Authors and Affiliations

  1. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    Hayley F. North, Jason Bruggemann, Rhoshel Lenroot, Thomas W. Weickert & Cynthia Shannon Weickert

  2. Neuroscience Research Australia, Randwick, Sydney, NSW, Australia

    Hayley F. North, Jason Bruggemann, Rhoshel Lenroot, Thomas W. Weickert & Cynthia Shannon Weickert

  3. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Parkville, VIC, Australia

    Vanessa Cropley, Avril M. Pereira, Andrew Zalesky, Chad Bousman & Christos Pantelis

  4. Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, VIC, Australia

    Vaidy Swaminathan & Suresh Sundram

  5. Mental Health Program,, Monash Health, Clayton, VIC, Australia

    Vaidy Swaminathan & Suresh Sundram

  6. Northern Psychiatry Research Centre, North Western Mental Health, Melbourne Health, Melbourne, VIC, Australia

    Suresh Sundram

  7. Molecular Psychopharmacology Laboratory, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia

    Suresh Sundram & Avril M. Pereira

  8. Department of Psychiatry and Behavioral Sciences, School of Medicine, University of New Mexico, Albuquerque, NM, USA

    Rhoshel Lenroot

  9. Department of Medical Genetics, Psychiatry, and Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada

    Chad Bousman

  10. Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, NY, 13210, USA

    Thomas W. Weickert & Cynthia Shannon Weickert

Authors
  1. Hayley F. North
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  2. Jason Bruggemann
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  3. Vanessa Cropley
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  4. Vaidy Swaminathan
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  6. Rhoshel Lenroot
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  7. Avril M. Pereira
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  8. Andrew Zalesky
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  9. Chad Bousman
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  10. Christos Pantelis
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  11. Thomas W. Weickert
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  12. Cynthia Shannon Weickert
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Contributions

Conceptualisation: HFN and CSW; methodology: all authors; formal analysis and investigation: HN, RL, VC, JB, TW, and CSW. Writing original draft preparation: HN and CSW; writing—review and editing: all authors; resources: VC, RL, CP, TWW, and CSW; supervision: CSW.

Corresponding author

Correspondence to Cynthia Shannon Weickert.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethics approval

This study was carried out in accordance with the Declaration of Helsinki after review at the University of New South Wales (HREC14265).

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All participants consented to participate in this study.

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North, H.F., Bruggemann, J., Cropley, V. et al. Increased peripheral inflammation in schizophrenia is associated with worse cognitive performance and related cortical thickness reductions. Eur Arch Psychiatry Clin Neurosci 271, 595–607 (2021). https://doi.org/10.1007/s00406-021-01237-z

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  • DOI: https://doi.org/10.1007/s00406-021-01237-z

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