Peripheral immune markers and antipsychotic non-response in psychosis

D. Enache, N. Nikkheslat, D. Fathalla, B.P. Morgan, S. Lewis, R. Drake, B. Deakin, J. Walters, S.M. Lawrie, A. Egerton, J.H. MacCabe, V. Mondelli

Research output: Contribution to journalArticlepeer-review


Background: Peripheral immune markers have previously been linked to a poor response to antipsychotic medication and more severe negative symptoms at the onset of psychosis. The present study investigated the association of blood cytokines and complement markers with the presence of antipsychotic non-response and symptom severity in patients with psychosis. Methods: This cross-sectional study recruited 94 patients with schizophrenia and other psychoses, of whom 47 were defined as antipsychotic responders and 47 as antipsychotic non-responders. In all subjects we measured plasma levels of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, and IFN-γ), complement markers (C1-inhibitor, C3, C4, C3a, C3b, Bb, factor D, C5a, terminal complement complex) and high sensitivity C-reactive protein (hsCRP). Symptom severity was recorded using the Positive and Negative Syndrome scale for Schizophrenia (PANSS). Binary logistic regression tested each immune marker as predictor of response status while covarying for relevant socio-demographic variables. Correlation analyses tested the association between immune markers and the severity of symptoms. Results: Interleukin (IL)-8 significantly predicted antipsychotic non-response (OR=24.70, 95% CI, 1.35–453.23, p = 0.03). Other immune markers were not associated with antipsychotic response. IL-6, IL-8, IL-10 and TNF-α significantly positively correlated with negative psychotic symptoms. Conclusions: Higher levels of IL-8 are associated with a poor response to antipsychotic treatment. Increased cytokines levels are specifically associated with more severe negative symptoms in patients with schizophrenia and other psychoses.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalSchizophrenia Research.
Early online date2 Mar 2021
Publication statusPublished - 1 Apr 2021


  • Antipsychotic response
  • Complement system
  • Cytokines
  • Inflammation
  • Negative symptoms
  • Schizophrenia


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