Immune-inflammatory markers and psychosis risk: A systematic review and meta-analysis

Błażej Misiak, Francesco Bartoli, Giuseppe Carrà, Bartłomiej Stańczykiewicz, Anna Gładka, Dorota Frydecka, Jerzy Samochowiec, Konrad Jarosz, Tomasz Hadryś, Brian J. Miller

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations


Subclinical inflammation has been associated with psychosis; however, it remains unknown whether this phenomenon appears also in the premorbid phase. Therefore, we performed a systematic review and meta-analysis of studies comparing peripheral blood levels of C-reactive protein (CRP) and cytokines between individuals at risk of psychosis and controls. Moreover, we tested the hypothesis that the levels of these markers may be different in high-risk converters versus non-converters. Two independent reviewers searched electronic databases until Dec 16th, 2020. After reviewing publication records, 16 studies (548 high-risk individuals and 559 controls) were included. Random-effects meta-analyses with Hedges’ g as the effect size estimate were performed. Individuals at clinical risk of psychosis had significantly higher levels of interleukin-6 (IL-6) compared to controls (g = 0.33, 95%CI: 0.06–0.60, p = 0.018). Heterogeneity was not significant in this subgroup analysis. Changes in the levels of IL-6 in subjects at familial risk of psychosis were not significant (g = 0.04, 95%CI: −0.24 to 0.31, p = 0.798). The use of antidepressants was associated with significantly higher levels of IL-6 in high-risk individuals (Beta = 1.56, 95%CI: 0.60–2.53, p = 0.001). No significant differences in the levels of immune-inflammatory markers were found between high-risk converters and non-converters. Our findings suggest that individuals at clinical risk of psychosis show subclinical inflammation in terms of elevated IL-6 levels. This phenomenon might be related to the use of antidepressants. The present meta-analysis does not support the usefulness of single immune-inflammatory markers in predicting transition to psychosis.

Original languageEnglish (US)
Article number105200
StatePublished - May 2021


  • Early intervention
  • Immunity
  • Inflammation
  • Psychotic disorders
  • Schizophrenia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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