Markers of Inflammation Are Generally Elevated in Schizophrenia-Spectrum Disorders

Patients with schizophrenia-spectrum disorders have differing inflammatory marker levels compared with healthy controls. These results from a systematic review and meta-analysis were published in The Lancet Psychiatry.

Investigators from the University of Queensland in Australia and Ludwig-Maximilians-Universität München in Germany searched publication databases from inception through March 2022 for studies reporting biomarkers for inflammation in schizophrenia-spectrum disorders. A total of 215 studies were included in this analysis.

Most studies (n=180) recruited patients with schizophrenia and overall, the studies included 13,952 patients with schizophrenia spectrum disorders and 10,969 healthy controls. The cases and controls had mean ages of 34.6 (SD, 12.2) and 33.9 (SD, 11.7) years, 62% and 56% were men, 35% and 27% were smokers, and they had BMIs of 25.2 (SD, 5.8) and 24.4 (SD, 4.6) kg/m², respectively.

In the pairwise meta-analysis, levels of 31 inflammatory markers were compared between cases and controls and all but 5 differed significantly (all P ≤.0029).

In the network meta-analysis of 13 markers with sufficient data, concentrations of inflammatory proteins were consistently elevated among cases with acute or chronic schizophrenia-spectrum disorders compared with controls. Specifically, elevations were observed in interleukin (IL)-1β, IL-1RA, soluble IL (sIL)-2R, IL-6, IL-8, IL-19, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP).

Inconsistent trends were observed for IL-2, IL-4, IL-12, and interferon (IFN)-. For IL-2, patients with acute schizophrenia-spectrum disorders had higher levels than controls but patients with chronic schizophrenia-spectrum disorders did not. For IL-4, IL-12, and IFN-, patients with acute schizophrenia-spectrum disorders had higher levels and those with chronic schizophrenia-spectrum disorders, lower levels, compared with controls.

Among the cases, the only significant group differences were observed in IL-6, IL-4, IL-12, and IFN-, in which higher levels were observed in acute schizophrenia-spectrum disorders compared with chronic schizophrenia-spectrum disorders.

Most comparisons did not have evidence of publication bias, except for comparisons of IL-1RA, sIL-2R, IL-6, and TNF-α levels. Pairwise and network meta-analyses had significant heterogeneity with most I² values greater than 80%.

These findings may have been limited as the comparisons with controls were primarily based on direct evidence whereas the comparisons between cases were based on indirect evidence.

Study authors concluded, “This study provides guidance for the framing of cytokines as potential state and trait biomarkers or to indicate a subgroup of cases with a greater inflammatory phenotype. These findings might lead to the repurposing of drugs, such as anti-inflammatory medications, as treatment adjuncts in [schizophrenia]-spectrum disorder. Ultimately, greater clarity of how inflammation is involved in the cause and pathophysiology of schizophrenia could foster the development of new targeted interventions aimed at illness prevention.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.