Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-analysis

BACKGROUND:A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and lymphoid line including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared to healthy controls have been lacking. METHODS:Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared to healthy controls were included. RESULTS:A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, SMD=0.35; 95%-CI: 0.24-0.46), granulocyte count (4 studies, SMD=0.57; 95%-CI: 0.12-1.01), neutrophile granulocyte count (21 studies, SMD=0.32; 95%-CI: 0.11-0.54), monocyte count (23 studies, SMD=0.40; 95%-CI: 0.23-0.56) and B lymphocyte count (10 studies, SMD=0.26; 95%-CI: 0.04-0.48). Additionally, the neutrophile/lymphocyte ratio (23 studies, SMD=0.40; 95%-CI: 0.19-0.60), the monocyte/lymphocyte ratio (9 studies, SMD=0.31; 95%-CI: 0.04-0.57), and the platelet/lymphocyte ratio (10 studies, SMD=0.23; 95%-CI: 0.03-0.43) were elevated. The CSF cell count showed similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95%-CI: -0.04 to 0.32). CONCLUSION:The results indicate a broad activation of the immune system in psychotic disorders with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors as BMI and smoking.