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Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia

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Neuroinflammation and Schizophrenia

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 44))

Abstract

In this article, we review current evidence linking immune dysfunction in schizophrenia and related psychotic disorders focusing particularly on circulating cytokines, oxidative stress and cellular markers of inflammation in various stages on illness from drug-naïve first episode psychosis to chronic schizophrenia. Acute psychotic episode is associated with low-grade systemic inflammation in some patients, as reflected by increased concentrations of cytokines and other inflammatory markers in peripheral blood. Evidence from general population-based longitudinal cohort studies reporting an association between elevated inflammatory markers in childhood/adolescence and risk of schizophrenia and related psychosis subsequently in adulthood suggest that inflammation could be a causal risk factor for psychosis rather than simply be a consequence of illness. Mendelian randomization studies also suggest that associations between IL-6, CRP and schizophrenia are likely to be causal. In addition, we discuss evidence for disruptions in oxidative stress markers and CSF cytokine levels in schizophrenia, and potential reasons for reported trans-diagnostic associations for inflammatory cytokines including role of early-life adversity/maltreatment. We argue that low-grade inflammation is a clinically useful feature, because it is associated with poor response to antipsychotic medication in first episode psychosis. We discuss clinical implications for immunological understanding of schizophrenia including scope for clinical trials of anti-inflammatory agents and notable gaps in current knowledge, and offer suggestions for future research.

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Abbreviations

ALSPAC:

Avon Longitudinal Study of Parents and Children

BBB:

Blood-brain barrier

CNS:

Central nervous system

CRP:

C-reactive protein

CSF:

Cerebrospinal fluid

FEP:

First episode psychosis

Glx:

Glutamate/glutamine ratio

GSH:

Glutathione

HPA:

Hypothalamic-pituitary-adrenal

IL-6:

Interleukin-6

IL-8:

Interleukin-8

MHC:

Major histocompatibility complex

ROS:

Reactive oxygen series

TNF-α:

Tumour necrosis factor alpha

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Acknowledgement

Dr. Khandaker acknowledges funding support from the Wellcome Trust (201486/Z/16/Z), MQ: Transforming Mental Health (MQDS17/40) and MRC, UK (MC_PC_17213).

Declaration of Interest

The authors have no competing financial interests in relation to the work described.

Author information

Authors and Affiliations

  1. Institute for Mental Health, University of Birmingham, Birmingham, UK

    Rachel Upthegrove

  2. Birmingham Early Intervention Service, Birmingham Women’s and Children’s NHS Trust, Birmingham, UK

    Rachel Upthegrove

  3. Department of Psychiatry, University of Cambridge, Cambridge, UK

    Golam M. Khandaker

  4. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK

    Golam M. Khandaker

Authors
  1. Rachel Upthegrove
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  2. Golam M. Khandaker
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Corresponding author

Correspondence to Rachel Upthegrove .

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Editors and Affiliations

  1. Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK

    Golam M. Khandaker

  2. Verhaltensneurobiologie, ETH Zürich, Schwerzenbach, Switzerland

    Urs Meyer

  3. Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK

    Peter B. Jones

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Upthegrove, R., Khandaker, G.M. (2019). Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia. In: Khandaker, G., Meyer, U., Jones, P. (eds) Neuroinflammation and Schizophrenia. Current Topics in Behavioral Neurosciences, vol 44. Springer, Cham. https://doi.org/10.1007/7854_2018_88

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