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

Max Clausen; Rune H B Christensen; Maria da Re; Michael E Benros

doi:10.1016/j.biopsych.2023.11.029

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

Biol Psychiatry. 2024 Jan 6:S0006-3223(24)00001-5. doi: 10.1016/j.biopsych.2023.11.029. Online ahead of print.

Authors

Max Clausen¹, Rune H B Christensen², Maria da Re³, Michael E Benros⁴

Affiliations

¹ Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
² Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.
³ Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Unit of Psychiatry, Department of Medicine, University of Udine, Udine, Italy.
⁴ Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: Michael.eriksen.benros@regionh.dk.

PMID: 38185237
DOI: 10.1016/j.biopsych.2023.11.029

Abstract

Background: A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has 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 with healthy control participants 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, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, -0.04 to 0.32).

Conclusions: 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 such as body mass index and smoking.

Keywords: B cells; Immune cells; Inflammation; Leukocytes; Psychosis; T cells.