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https://doi.org/10.1371/journal.pone.0155631
Title: | Peripheral immune cell populations associated with cognitive deficits and negative symptoms of treatment-resistant schizophrenia | Authors: | Fernandez-Egea E. Vértes P.E. Flint S.M. Turner L. Mustafa S. Hatton A. Smith K.G.C. Lyons P.A. Bullmore E.T. |
Keywords: | biological marker chemokine receptor CXCR5 clozapine dopamine 3 receptor dopamine receptor HLA DR antigen risperidone dopamine 3 receptor DRD3 protein, human HLA DR antigen neuroleptic agent adult Article B lymphocyte case control study CD4+ T lymphocyte cell activation cell population clinical article cognitive defect controlled study cross-sectional study dopaminergic transmission female flow cytometry gene expression human immunocompetent cell immunophenotyping male memory T lymphocyte mental patient monocyte natural killer cell negative syndrome receptor gene regulatory T lymphocyte schizophrenia venous blood biosynthesis blood CD4 lymphocyte count Cognitive Dysfunction cytology dendritic cell genetics immunological memory immunology lymphocyte activation middle aged schizophrenia T lymphocyte subpopulation young adult Adult Antipsychotic Agents Biomarkers Case-Control Studies CD4 Lymphocyte Count Clozapine Cognitive Dysfunction Cross-Sectional Studies Dendritic Cells Female Flow Cytometry HLA-DR Antigens Humans Immunologic Memory Killer Cells, Natural Lymphocyte Activation Male Middle Aged Receptors, Dopamine D3 Schizophrenia T-Lymphocyte Subsets T-Lymphocytes, Regulatory Young Adult |
Issue Date: | 2016 | Citation: | Fernandez-Egea E., Vértes P.E., Flint S.M., Turner L., Mustafa S., Hatton A., Smith K.G.C., Lyons P.A., Bullmore E.T. (2016). Peripheral immune cell populations associated with cognitive deficits and negative symptoms of treatment-resistant schizophrenia. PLoS ONE 11 (5) : e0155631. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0155631 | Rights: | Attribution 4.0 International | Abstract: | Background: Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to be peripheral immune system phenotypes that are measurable in blood cells as biomarkers of psychotic states. Methods: We used multi-parameter flow cytometry of venous blood to quantify and determine the activation state of 73 immune cell subsets for 18 patients with chronic schizophrenia (17 treated with clozapine), and 18 healthy volunteers matched for age, sex, BMI and smoking. We used multivariate methods (partial least squares) to reduce dimensionality and define populations of differentially co-expressed cell counts in the cases compared to controls. Results: Schizophrenia cases had increased relative numbers of NK cells, naïve B cells, CXCR5+ memory T cells and classical monocytes; and decreased numbers of dendritic cells (DC), HLA-DR+ regulatory T-cells (Tregs), and CD4+ memory T cells. Likewise, within the patient group, more severe negative and cognitive symptoms were associated with decreased relative numbers of dendritic cells, HLA-DR+ Tregs, and CD4+ memory T cells. Motivated by the importance of central nervous system dopamine signalling for psychosis, we measured dopamine receptor gene expression in separated CD4+ cells. Expression of the dopamine D3 (DRD3) receptor was significantly increased in clozapine-treated schizophrenia and covaried significantly with differentiated T cell classes in the CD4+ lineage. Conclusions: Peripheral immune cell populations and dopaminergic signalling are disrupted in clozapinetreated schizophrenia. Immuno-phenotypes may provide peripherally accessible and mechanistically specific biomarkers of residual cognitive and negative symptoms in this treatment-resistant subgroup of patients. © 2016 Fernandez-Egea et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161568 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0155631 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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