Levels of cytokines in the cerebrospinal fluid of patients with psychotic disorders compared to individually matched healthy controls

• Published in: Brain, behavior, and immunity behavior, and immunity, 2024-03, Vol.117, p.167-174
• Main Authors: Jeppesen, Rose, Borbye-Lorenzen, Nis, Christensen, Rune Haubo Bojesen, Sørensen, Nina Vindegaard, Köhler-Forsberg, Ole, Skogstrand, Kristin, Benros, Michael Eriksen
• Format: Article
• Language: English
• Subjects: Cerebrospinal fluid; CSF; Inflammation; Psychosis; Schizophrenia
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.12.035

•Increased levels of cerebrospinal fluid (CSF) cytokines have previously been found in psychotic disorders.•Most previous studies have small sample sizes and none have individually matched controls.•This study represents the largest to date on cytokines in the CSF.•We found no significant difference in neither interleukine-6 (IL-6) nor IL-8 between patients and individually matched controls.•We found higher levels of CSF IL-4, a trend towards higher IFN-γ and lower IL-16 before correction for multiple testing, but further studies are needed to confirm this. Increased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders. Patients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22–29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria’s except for the psychiatric diagnoses. All participants were aged 18–50 years and individuals with neurological or immunological disorders were excluded. CSF cytokines were analyzed with MesoScale V-PLEX neuroinflammation panel. Co-primary outcomes were CSF interleukin-6 (IL-6) and IL-8. We included 104 patients and 104 healthy controls, matching on age, sex and BMI. No significant differences were found for the primary outcomes IL-6 (relative mean difference (MD): 0.97, 95 %CI: 0.84–1.11, p = 0.637) or IL-8 (MD: 1.01, 95 %CI: 0.93–1.09, p = 0.895). Secondary analyses found patients to have higher IL-4 (MD: 1.30, 95 %CI: 1.04–1.61, p = 0.018), a trend towards higher IFN-γ (MD: 1.26, 95 %CI: 0.99–1.59, p = 0.056), and lower IL-16 (MD: 0.83, 95 %CI: 0.74–0.94, p = 0.004) than healthy controls, though not significant after correction for multiple testing. IL-8 and IL-16 were found positively associated with CSF white blood cells and CSF/serum albumin ratio. The study was limited by 77.9 % of the patients being on antipsychotic treatment at time of intervention, and that levels of nine of the 26 cytokines were below lower limit of detection (LLOD) in >50 % of samples; however, for the primary outcomes IL-6 and IL-8 more than 99.5 % of the samples were above LLOD and for IL-8 all samples exceeded the lower limit of quantification (LLOQ). We found no evidence of increased IL-6 and IL-8 in patients with