Innate immune cells and C-Reactive protein in acute First-Episode psychosis and schizophrenia: relationship to psychopathology and treatment
Open accessAbstract
Innate immunity has been linked to initiation of Alzheimer's disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte-macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale [PANSS]) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = -0.161, P = .036). In FEP, normalization of neutrophils (ρ = -0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.
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The observed differences in cell proportions may reflect effects of various antipsychotic medications or a recruitment bias whereby patients with low granulocytes are not prescribed clozapine.
“Importantly, the differences we observe may actually reflect the effects of various antipsychotic medications that have been previously shown to influence cell proportions in blood (Steiner et al., 2019) or a recruitment bias whereby patients with low levels of granulocytes are not prescribed clozapine given the risk of agranulocytosis.”
From DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia (2021) · cites this paper as Steiner et al., 2019
Variations in the number of neutrophils is a potential marker of disease severity.
“suggesting that variations in the number of neutrophils is a potential marker of disease severity (Steiner et al., 2019).”
From DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia (2021) · cites this paper as Steiner et al., 2019
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- Authors
- Steiner, J., Frodl, T., Schiltz, K., Dobrowolny, H., Jacobs, R., Fernandes, B. S., Guest, P. C., Meyer-Lotz, G., Borucki, K., Bahn, S., Bogerts, B., Falkai, P., & Bernstein, H.-G.
- Affiliations
- Laboratory of Translational Psychiatry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
- German Center for Neurodegenerative Diseases (DE)
- Ludwig-Maximilians-Universität München (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Medizinische Hochschule Hannover (DE)
- University of Toronto (CA)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- University of Cambridge (GB)
- Center for Behavioral Brain Sciences (DE)
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-08-29
- Volume
- 46
- Issue
- 2
- Pages
- 363-373
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC7442383
- OpenAlex
- W2970478205
- Cited by
- 123
- References
- 45
- Citations by year
- 2026: 4 · 2025: 20 · 2024: 26 · 2023: 23 · 2022: 17 · 2021: 24 · 2020: 9
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Schizophrenia Bulletin (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by-nc)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- DZNE Pub (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- innate immunity, C-reactive protein
- MeSH terms
- Adult, C-Reactive Protein, Female, Follow-Up Studies, Humans, Immunity, Innate, Leukocyte Count, Leukocytes, Male, Middle Aged, Psychotic Disorders, Schizophrenia, Antipsychotic Agents, Young Adult
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