Please use this identifier to cite or link to this item: 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
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