T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment

Department of Psychiatry and Psychotherapy Ludwig-Maximilians-University, München, Germany.
Psychiatry Research (Impact Factor: 2.47). 09/2007; 152(2-3):173-80. DOI: 10.1016/j.psychres.2006.06.004
Source: PubMed


Schizophrenia is associated with alterations of the immune system. There are, however, only limited data dealing with immune parameters in unmedicated schizophrenic patients and the course of these parameters during treatment. In this study, we monitored CD19+ (B)- and CD3+ (T)-lymphocytes in the course of antipsychotic treatment. Forty patients diagnosed with an acute exacerbation of schizophrenia were tested before and after 3 days, 2 weeks, 4 weeks and 3 months of treatment with antipsychotics. The percentages of CD19+- and CD3+ -lymphocytes were analysed by flow cytometry using fluorescence conjugated anti-CD19 and anti-CD3 antibodies. Twenty healthy volunteers served as controls. In the acute state of psychosis, a significant reduction of the CD3+ -lymphocyte subpopulation was observed, while the percentage of CD19(+)-lymphocytes was increased. Both subpopulations levelled to those of the control group in the course of treatment. As expected, the levels of the immune parameters did not change in the healthy controls during the course of the study. The observed alterations of the CD19+ - and CD3+ -lymphocytes in the acute state of psychosis especially in patients with the paranoid subtype of schizophrenia, and the "normalization" during the observation period are discussed under the aspect of the immune hypothesis of schizophrenia, in particular of the type-1/type-2 imbalance hypothesis.

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    • "Pathogenetic mechanisms that result from schizophrenia have been associated with abnormal activation of the immune system (Muller and Schwarz, 2007, 2010; Miller et al., 2011). Immune alterations can be found within the brain and cerebrospinal fluid, as well as in the blood serum and leukocytes of schizophrenia patients (Maino et al., 2007; Potvin et al., 2008; Chan et al., 2011; Drexhage et al., 2011a, 2011b; Miller et al., 2011; Schwarz et al., 2012). These findings suggest that systemic inflammatory alterations occur in schizophrenic patients. "
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    ABSTRACT: Objective: The main goal of the present study was to analyze levels of cytokines of the interleukin family (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF-α), and vascular endothelial and endothelial growth factors (VEGF and EGF), in the blood samples of first-episode psychosis (FEP) patients before and seven months after the start of antipsychotic medication use. Method: 38 anti-psychotic medication-naïve FEP patients and 37 healthy controls (HC) were recruited. Biochip array technology was used to measure cytokines and growth factors. Results: The comparison of these markers in FEP patients and HC revealed significantly higher levels of EGF, IL-4 and IL-6 and significantly lower level of IL-1β in FEP patients before the antipsychotic treatment. Multiple regression analysis demonstrated significant correlations between FEP and EGF, IL-1β and smoking. Treatment with antipsychotic drugs resulted in a statistically significant amelioration of the symptoms of psychosis, but caused a significant increase in the body mass index (BMI) of patients. Levels of EGF, IL-2, VEGF, IL-6, IFN-γ, IL-4, IL-8 and IL-1α were significantly lower in treated FEP patients compared to premedication levels. Conclusions: According to the present study, EGF and IL-1β are markers of FEP. Antipsychotic drug treatment resulted in a significant clinical improvement of FEP patients and the suppression of positive symptoms was correlated with the decreased levels of EGF, IL-2 and IL-4. EGF was the strongest marker of FEP and treatment efficiency among the measured cytokines and growth factors.
    Schizophrenia Research 09/2015; DOI:10.1016/j.schres.2015.08.027 · 3.92 Impact Factor
    • "14 Mazzarello et al. 2004 Schizophrenia patients (n=24) Decreased percentage of CD8+ and higher CD4+ / CD8+ ratio were reported. 15 Matloubi et al. 2007 Drug-free schizophrenia patients (n=30) Lower T cell responses to mitogen 16 Maino et al. 2007 Unmedicated Schizophrenia patients (n=40) In the acute state of psychosis, a significant reduction of the CD3+lymphocyte subpopulation and increased percentage of CD19(+)lymphocytes were observed. 17 Craddock et al. 2007 In vitro studies of peripheral blood T cells derived from schizophrenia patients "
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    ABSTRACT: Schizophrenia is a severe and highly complex neurodevelopmental disorder with an unknown etiopathology. Recently, immunopathogenesis has emerged as one of the most compelling etiological models of schizophrenia. Over the past few years considerable research has been devoted to the role of innate immune responses in schizophrenia. The findings of such studies have helped to conceptualize schizophrenia as a chronic low-grade inflammatory disorder. Although the contribution of adaptive immune responses has also been emphasized, however, the precise role of T cells in the underlying neurobiological pathways of schizophrenia is yet to be ascertained comprehensively. T cells have the ability to infiltrate brain and mediate neuro-immune cross-talk. Conversely, the central nervous system and the neurotransmitters are capable of regulating the immune system. Neurotransmitter like dopamine, implicated widely in schizophrenia risk and progression can modulate the proliferation, trafficking and functions of T cells. Within brain, T cells activate microglia, induce production of pro-inflammatory cytokines as well as reactive oxygen species and subsequently lead to neuroinflammation. Importantly, such processes contribute to neuronal injury/death and are gradually being implicated as mediators of neuroprogressive changes in schizophrenia. Antipsychotic drugs, commonly used to treat schizophrenia are also known to affect adaptive immune system; interfere with the differentiation and functions of T cells. This understanding suggests a pivotal role of T cells in the etiology, course and treatment of schizophrenia and forms the basis of this review.
    Journal of Neuroimmune Pharmacology 07/2015; DOI:10.1007/s11481-015-9626-9 · 4.11 Impact Factor
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    • "This decreasing has also been found in patients with breast cancer having a higher hopeful attitude [70] or in patients that receive psychological treatment before surgery in order to decrease their surgical anxiety [71]. However, B cells are increased in patients with acute schizophrenia [72] or university students under stress periods [73]. In laboratory animals (mouse) with experimental allergic or autoimmune encephalomyelitis [74, 75], as well as in multiple sclerosis patients [76] has also been found the presence of CD134+ cells localized in the active lesions. "
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    ABSTRACT: The aging process involves a decline in immune functioning that renders elderly people more vulnerable to disease. In residential programs for the aged, it is vital to diminish their risk of disease, promote their independence, and augment their psychological well-being and quality of life. We performed a randomized controlled study, evaluating the ability of a relaxation technique based on Benson’s relaxation response to enhance psychological well-being and modulate the immune parameters of elderly people living in a geriatric residence when compared to a waitlist control group. The study included a 2-week intervention period and a 3-month follow-up period. The main outcome variables were psychological well-being and quality of life, biomedical variables, immune changes from the pre-treatment to post-treatment and follow-up periods. Our findings reveal significant differences between the experimental and control groups in CD19, CD71, CD97, CD134, and CD137 lymphocyte subpopulations at the end of treatment. Furthermore, there was a decrease in negative affect, psychological discomfort, and symptom perception in the treatment group, which increased participants’ quality of life scores at the three-month follow-up. This study represents a first approach to the application of a passive relaxation technique in residential programs for the elderly. The method appears to be effective in enhancing psychological well-being and modulating immune activity in a group of elderly people. This relaxation technique could be considered an option for achieving health benefits with a low cost for residential programs, but further studies using this technique in larger samples of older people are needed to confirm the trends observed in the present study. Trial registration International Standard Randomised Controlled Trial Number Register ISRCTN85410212
    BMC Complementary and Alternative Medicine 08/2014; 14(1):311. DOI:10.1186/1472-6882-14-311 · 2.02 Impact Factor
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