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

• Published in: Psychoneuroendocrinology Vol. 127; p. 105200
• Main Authors: Misiak, Błażej, Bartoli, Francesco, Carrà, Giuseppe, Stańczykiewicz, Bartłomiej, Gładka, Anna, Frydecka, Dorota, Samochowiec, Jerzy, Jarosz, Konrad, Hadryś, Tomasz, Miller, Brian J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2021
• Subjects: Biomarkers - blood; C-Reactive Protein - analysis; Case-Control Studies; Early intervention; Humans; Immunity; Inflammation; Interleukin-6 - blood; Psychotic disorders; Psychotic Disorders - blood; Psychotic Disorders - epidemiology; Risk Assessment; Schizophrenia; Psychotic disorders; Schizophrenia; Early intervention; Inflammation; Immunity
• ISSN: 0306-4530; 1873-3360; 1873-3360
• DOI: 10.1016/j.psyneuen.2021.105200

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. •Clinical risk of psychosis might be related to elevated interleukin-6 (IL-6) levels.•The use of antidepressants may be related to IL-6 levels in at-risk individuals.•The levels of single inflammatory markers do not predict transition to psychosis.