Cytokine Dysregulation in Schizophrenia Spectrum Disorders
Summary
Schizophrenia spectrum disorders are increasingly recognised as involving aberrant immune signalling, with dysregulated cytokine networks contributing to both neurodevelopmental and neurodegenerative processes. Patients frequently display elevated pro-inflammatory cytokines such as interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) alongside variable changes in anti-inflammatory mediators like interleukin-10 (IL-10). These imbalances may arise from genetic predisposition, early-life stressors and peripheral inflammagens crossing a compromised blood–brain barrier. Within the central nervous system, activated microglia amplify cytokine release, modulating synaptic pruning and neurotransmitter metabolism via the kynurenine pathway. Clinically, cytokine profiles correlate with symptom domains—pro-inflammatory dominance associates with negative and cognitive symptoms, whereas mixed profiles may underlie acute psychotic exacerbations. Peripheral markers such as soluble urokinase plasminogen activator receptor (suPAR) and C-reactive protein also reflect systemic inflammation and predict disease onset or treatment resistance. Elucidation of these pathways offers prospects for stratified immunotherapies, ranging from anti-cytokine antibodies to repurposed antibiotics with immunomodulatory effects, and may guide personalised interventions across global healthcare settings.
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Cytokine Dysregulation in Schizophrenia Spectrum Disorders publication trend
The graph below shows the total number of articles in cytokine dysregulation in schizophrenia spectrum disorders across all publications each year (not limited to Nature Index journals).
Technical terms
Cytokine: Small protein released by immune cells that mediates intercellular communication during inflammatory and immune responses.
Pro-inflammatory cytokine: Subset of cytokines that promote and sustain inflammation, exemplified by IL-6, TNF-α and IFN-γ.
Anti-inflammatory cytokine: Cytokine that dampens immune activation and limits tissue damage, for example IL-10.
Microglia: Resident immune cells of the central nervous system that regulate synaptic homeostasis and mount inflammatory reactions.
Blood–brain barrier: Selective endothelial interface controlling molecular and cellular passage between bloodstream and neural tissue.
Kynurenine pathway: Metabolic cascade converting tryptophan into neuroactive metabolites that influence glutamatergic neurotransmission and neurotoxicity.
References
- Associations between plasma inflammatory markers and psychotic disorder, depressive disorder and generalised anxiety disorder in early adulthood: A nested case-control study. Brain Behavior and Immunity (2023).
- Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial. Translational Psychiatry (2023).
- Immune-inflammatory markers and psychosis risk: A systematic review and meta-analysis. Psychoneuroendocrinology (2021).
- Effects of inflammation on the kynurenine pathway in schizophrenia — a systematic review. Journal of Neuroinflammation (2020).
- Cytokine Alterations in Schizophrenia: An Updated Review. Frontiers in Psychiatry (2019).
- Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis. Schizophrenia Bulletin (2015).
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