| 1 | World J. Biol. Psychiatry 2004 Jan 5: 33-7 |
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| PMID | 15048633 |
| Title | Search for atypical lymphocytes in schizophrenia. |
| Abstract | The existence of atypical lymphocytes with specific morphological characteristics in the peripheral blood of schizophrenic patients has been suggested in several reports over the last 40 years. In our study this observation was examined not only by using the formerly applied method of light microscopy for general cell distribution and lymphocyte morphology but also by applying flow cytometry, a well established immunological method for lymphocyte patterns such as lymphocyte subgroups and lymphocyte activity. In contrast to the previously published data, our results demonstrated no differences in cell distribution (lymphocytes, polymorphonuclear cells, eosinophil and basophil granulocytes, monocytes), lymphocyte morphology ("atypical lymphocytes" vs. "normal lymphocytes"), distribution of lymphocyte-subtypes (T-cells (CD3(+)), T-helper-cells (CD3(+)/CD4(+)), cytotoxic T-cells (CD3(+)/CD8(+)), B-cells (CD19(+)), NK-cells (CD3(-)/CD56(+))) or state of T-lymphocyte activity (CD25(+) or HLA-DR(+)-cells) in schizophrenic patients compared to healthy controls. We suggest that possible immunological alterations in schizophrenia do not correlate with morphological characteristics of lymphocytes observable by light microscopy or an altered state activity of T-lymphocytes examined by flow cytometric parameters. Further studies should concentrate on intracellular and functional aspects of the different lymphocyte subgroups. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | World J. Biol. Psychiatry 2004 Jan 5: 33-7 |
|---|
| PMID | 15048633 |
| Title | Search for atypical lymphocytes in schizophrenia. |
| Abstract | The existence of atypical lymphocytes with specific morphological characteristics in the peripheral blood of schizophrenic patients has been suggested in several reports over the last 40 years. In our study this observation was examined not only by using the formerly applied method of light microscopy for general cell distribution and lymphocyte morphology but also by applying flow cytometry, a well established immunological method for lymphocyte patterns such as lymphocyte subgroups and lymphocyte activity. In contrast to the previously published data, our results demonstrated no differences in cell distribution (lymphocytes, polymorphonuclear cells, eosinophil and basophil granulocytes, monocytes), lymphocyte morphology ("atypical lymphocytes" vs. "normal lymphocytes"), distribution of lymphocyte-subtypes (T-cells (CD3(+)), T-helper-cells (CD3(+)/CD4(+)), cytotoxic T-cells (CD3(+)/CD8(+)), B-cells (CD19(+)), NK-cells (CD3(-)/CD56(+))) or state of T-lymphocyte activity (CD25(+) or HLA-DR(+)-cells) in schizophrenic patients compared to healthy controls. We suggest that possible immunological alterations in schizophrenia do not correlate with morphological characteristics of lymphocytes observable by light microscopy or an altered state activity of T-lymphocytes examined by flow cytometric parameters. Further studies should concentrate on intracellular and functional aspects of the different lymphocyte subgroups. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Eur Arch Psychiatry Clin Neurosci 2004 Feb 254: 14-22 |
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| PMID | 14991374 |
| Title | COX-2 inhibition as a treatment approach in schizophrenia: immunological considerations and clinical effects of celecoxib add-on therapy. |
| Abstract | Recent advances in immunological research regarding the differentiation between the type-1 and type-2 immune response are discussed. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of type-2 monocytes/macrophages, too. On the contrary, several parameters of the specific cellular immune system are blunted, e. g. the decreased type-1 related immune parameters in schizophrenic patients. This study was performed as a double-blind, placebo-controlled, randomized evaluation of risperidone and celecoxib versus risperidone and placebo. Fifty schizophrenic patients were included in the study: 25 patients received risperidone and placebo, and 25 patients received risperidone and celecoxib for 5 weeks after the wash-out period. The treatment effect was calculated by ANCOVA. In parallel, serum levels of sTNF-R1 and sIL- 2R, and the percentages of CD3(+)-, CD4(+)-, and CD19(+) lymphocytes were estimated. As expected, both groups of schizophrenic patients showed significant improvement. However, the celecoxib add-on therapy group showed a significant group effect in the PANSS total score. The cytokines and lymphocytes reflected the type-1/type-2 balancing effects of COX-2 inhibitors. Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to the total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug shows beneficial effects on the symptomatology of schizophrenia indicates that immune dysfunction in schizophrenia is not just an epiphenomenon, but related to the pathomechanism of the disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Eur Arch Psychiatry Clin Neurosci 2004 Feb 254: 14-22 |
|---|
| PMID | 14991374 |
| Title | COX-2 inhibition as a treatment approach in schizophrenia: immunological considerations and clinical effects of celecoxib add-on therapy. |
| Abstract | Recent advances in immunological research regarding the differentiation between the type-1 and type-2 immune response are discussed. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of type-2 monocytes/macrophages, too. On the contrary, several parameters of the specific cellular immune system are blunted, e. g. the decreased type-1 related immune parameters in schizophrenic patients. This study was performed as a double-blind, placebo-controlled, randomized evaluation of risperidone and celecoxib versus risperidone and placebo. Fifty schizophrenic patients were included in the study: 25 patients received risperidone and placebo, and 25 patients received risperidone and celecoxib for 5 weeks after the wash-out period. The treatment effect was calculated by ANCOVA. In parallel, serum levels of sTNF-R1 and sIL- 2R, and the percentages of CD3(+)-, CD4(+)-, and CD19(+) lymphocytes were estimated. As expected, both groups of schizophrenic patients showed significant improvement. However, the celecoxib add-on therapy group showed a significant group effect in the PANSS total score. The cytokines and lymphocytes reflected the type-1/type-2 balancing effects of COX-2 inhibitors. Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to the total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug shows beneficial effects on the symptomatology of schizophrenia indicates that immune dysfunction in schizophrenia is not just an epiphenomenon, but related to the pathomechanism of the disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Psychiatry Res 2007 Aug 152: 173-80 |
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| PMID | 17448544 |
| Title | T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Psychiatry Res 2007 Aug 152: 173-80 |
|---|
| PMID | 17448544 |
| Title | T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Mar 33: 214-9 |
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| PMID | 19059449 |
| Title | The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder. |
| Abstract | Bipolar disorder (BPD) and schizophrenia (SCZ) are severe disorders representing an enormous social, familiar and individual burden, being SCZ the most disabling psychiatric disorder characterized by psychosis and cognitive impairment. It is well known that SCZ and BPD are associated with abnormalities in dopamine signaling pathway. Recent data in the literature have demonstrated altered expression levels of some proteins involved in the modulation of this pathway in both brain and peripheral tissues. It was shown that protein and mRNA levels of dopamine and cAMP regulated phosphoprotein (DARPP-32) were downregulated in dorsolateral prefrontal cortex (DLPFC) of patients with SCZ or BPD when compared to controls. Due to the difficulty to access brain tissue and the absence of objective laboratory tests for bio-markers, we measured DARPP-32 expression in blood cell sub-populations (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) taking advantage of the close relation of nervous and immune systems. Using flow cytometry as the analytical method, our results have shown that the DARPP-32 expression was diminished in CD4+ T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and was also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. These results showed that DARPP-32 expression in immune cells agrees with reports of reduced DARPP-32 protein in the DLPFC of BPD or SCZ patients. Our data suggest that DARPP-32 expression in PBMC could be used as a source of bio-markers to help in the treatment response of neuropsychiatry disorders as a window to the changes in the brain of those patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Mar 33: 229-34 |
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| PMID | 19091302 |
| Title | Expression of neuronal calcium sensor-1 (NCS-1) is decreased in leukocytes of schizophrenia and bipolar disorder patients. |
| Abstract | schizophrenia (SCZ) and bipolar disorder (BPD) are severe illnesses representing an enormous social, familiar and individual burden that affect 1% of the population world-wide. Several evidences indicate abnormalities of the dopamine system in both SCZ and BPD. Neuronal calcium sensor-1 (NCS-1) is a protein that has many functions in neurotransmission such as inhibition of dopamine D(2) receptor desensitization, regulation of ionic channels and enhancement of exocytosis of neurotransmitters. In addition, NCS-1 protein expression and mRNA levels were found increased in pre-frontal cortex (PFC) of SCZ and BPD patients. NCS-1 expression in neural and neuroendocrine cells is well documented and, recently, it was shown that NCS-1 is also expressed in mast cells and neutrophils. NCS-1 has important functions in mast cells since it stimulates Fc epsilon RI-triggered exocytosis and the release of arachidonic acid metabolites. Then, due to the known close relation between the nervous and immune systems, we sought to investigate the NCS-1 expression in lymphocytes and monocytes (CD4+ T lymphocytes, CD56+ NK cells, CD19+ B lymphocytes and CD14+ monocytes) of SCZ and BPD patients. Using flow cytometry, our results have shown that NCS-1 expression was diminished in CD4+T lymphocytes, CD19+ B lymphocytes and CD14+ monocytes of BPD patients and also decreased in CD4+ T lymphocytes and CD56+ NK cells of SCZ patients. Results suggest that immune cells might be a cellular model for studies with SCZ and BPD patients considering NCS-1 functions. Efforts need to be done to investigate the motive of the decreased percentage of immune cells expressing NCS-1 in patients with SCZ and BPD. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Eur Arch Psychiatry Clin Neurosci 2010 Oct 260: 509-18 |
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| PMID | 20107825 |
| Title | Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. |
| Abstract | Previous studies of lymphocyte distribution in schizophrenia have yielded inconsistent results, as summarized in the present study. Based on our own original data, potential confounds that might explain these variations are analyzed and discussed. Blood samples from 26 patients with acute paranoid schizophrenia were investigated in comparison with 32 matched healthy controls by flow cytometry (CD3, CD4, CD8, CD19, and CD56 phenotyping). A subgroup of drug-free patients was followed up after 6 weeks of treatment. Cotinine levels and the free cortisol index (FCI) were provided in order to control for medication, smoking, and stress. Cotinine levels correlated with natural killer (NK) cell counts (CD3?/CD56(+): r = -0.383, P = 0.003) while the FCI was related to B cell numbers (CD19(+): r = 0.390, P = 0.003). Considering these covariates, a lower level of T helper cells (P = 0.010), a reduced CD4/CD8 ratio (P = 0.029), and elevated B cells (P = 0.008) were found during acute psychosis. After 6 weeks of medication, an inverse pattern was observed in initially drug-free patients: total T cell (P = 0.005), T helper (P = 0.003), and T suppressor/cytotoxic cells (P = 0.005) increased, while B cell counts declined (P = 0.049). In conclusion, acute paranoid schizophrenia may be accompanied by a reduced T cell defense and a shift towards B cell immunity, which normalizes in response to treatment. In addition to disease stage or subtype and medication, cigarette smoking and stress are important co-factors. |
| SCZ Keywords | schizophrenia, schizophrenic |