| 1 | Mol. Psychiatry 2001 Jul 6: 481-91 |
|---|---|
| PMID | 11443538 |
| Title | Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies--the key marker triplet determining infection and prevailing in severe mood disorders. |
| Abstract | Borna disease virus (BDV), a unique genetically highly conserved RNA virus (Bornaviridae; Mononegavirales), preferentially targets neurons of limbic structures causing behavioral abnormalities in animals. Markers and virus in patients with affective disorders and schizophrenia have raised worldwide interest. A persistent infection was suggestive from follow-up studies, but inconstant detectability weakened a possible linkage.This study for the first time discloses that detection gaps are caused by BDV-specific circulating immune complexes (CIC), and their interplay with free antibodies and plasma antigens (p40/p24). Screening 3000 sera each from human and equine patients over the past 4 years by new enzyme immunoassays (EIAs) revealed that BDV-CICs indicate 10 times higher infection rates (up to 30% in controls, up to 100% in patients) than did previous serology. Persistence of high amounts of CICs and plasma antigens correlates with severity of depression. Even BDV RNA could be detected in plasma samples with strong antigenemia. Our discovery not only explains the course of persistent infection, but offers novel easy-to-use diagnostic tools by which new insights into BDV-related etiopathogenesis of disease and epidemiology are possible. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Zh Nevrol Psikhiatr Im S S Korsakova 2004 -1 104: 39-45 |
| PMID | 15270298 |
| Title | [A change of immune profile of patients with schizophrenia during treatment]. |
| Abstract | Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Zh Nevrol Psikhiatr Im S S Korsakova 2004 -1 104: 39-45 |
| PMID | 15270298 |
| Title | [A change of immune profile of patients with schizophrenia during treatment]. |
| Abstract | Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 55-60 |
| PMID | 15875944 |
| Title | [Concentration and protein composition of circulating immune complexes in the blood of patients with schizophrenia and subjects with positive familial history of disease]. |
| Abstract | A comparative study of blood serum concentrations and pathogenic properties of circulating immune complexes (CIC), along with identification of their protein composition, was conducted in 45 patients with schizophrenia, 15 their healthy relatives and 39 normal controls. In patients and their relatives, mean concentration of small CIC was within the normal range, while concentrations of giant, large and middle CIC were higher than those of the controls (p<0.001). Over 80% of schizophrenic patients and their relatives had pathogenic immune complexes in the circulation. Clinical and immunologic analysis of patients with schizophrenia revealed a correlation between the illness duration and CIC concentration for all sizes. Smokers had significantly lower levels of small CIC comparing to non-smokers. Determination of CIC composition in patients and relatives revealed a presence of specific proteins in the immune complexes with molecular weights of 36 and 25 kDa. The results suggest genetic determination of autoimmune processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 55-60 |
| PMID | 15875944 |
| Title | [Concentration and protein composition of circulating immune complexes in the blood of patients with schizophrenia and subjects with positive familial history of disease]. |
| Abstract | A comparative study of blood serum concentrations and pathogenic properties of circulating immune complexes (CIC), along with identification of their protein composition, was conducted in 45 patients with schizophrenia, 15 their healthy relatives and 39 normal controls. In patients and their relatives, mean concentration of small CIC was within the normal range, while concentrations of giant, large and middle CIC were higher than those of the controls (p<0.001). Over 80% of schizophrenic patients and their relatives had pathogenic immune complexes in the circulation. Clinical and immunologic analysis of patients with schizophrenia revealed a correlation between the illness duration and CIC concentration for all sizes. Smokers had significantly lower levels of small CIC comparing to non-smokers. Determination of CIC composition in patients and relatives revealed a presence of specific proteins in the immune complexes with molecular weights of 36 and 25 kDa. The results suggest genetic determination of autoimmune processes in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Iran J Immunol 2007 Mar 4: 32-7 |
| PMID | 17652841 |
| Title | Decreased T cell response to mitogen and increased anti-cytoplasmic antibody in drug-free schizophrenic patients. |
| Abstract | Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In recent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. To investigate the T cell response to phytohaemagglutinin (PHA) and determine the serum levels of anti-nuclear antibody (ANA), anti-cytoplasmic antibody (ACA), and circulating immune complexes (CIC) in schizophrenic patients. A total of 30 drug-free schizophrenic patients and 42 healthy controls were enrolled in this study. T cell proliferation in response to PHA was measured using Methyl Thiazol Tetrazolium test. ANA and ACA were measured by indirect immunofluorescence. CIC concentration was determined using poly ethylene glycol precipitation assay. Mean PHA response was 1.96 +/- 0.83 in patients and 3.72 +/- 1.39 in healthy controls (p< 0.001). ANA and CIC concentrations were not significantly different between two groups. In addition, ACA was detected only in patients. Increased production of ACA together with lower T cell response to mitogens in our patients provides evidence for the involvement of autoimmune mechanisms in the pathogenesis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Iran J Immunol 2007 Mar 4: 32-7 |
| PMID | 17652841 |
| Title | Decreased T cell response to mitogen and increased anti-cytoplasmic antibody in drug-free schizophrenic patients. |
| Abstract | Apart from genetic and environmental factors, activation of autoreactive mechanisms has been proposed to play a role in the pathogenesis of schizophrenia. In recent years, considerable work has been carried out to understand the role and contribution of the immune system in this disease. To investigate the T cell response to phytohaemagglutinin (PHA) and determine the serum levels of anti-nuclear antibody (ANA), anti-cytoplasmic antibody (ACA), and circulating immune complexes (CIC) in schizophrenic patients. A total of 30 drug-free schizophrenic patients and 42 healthy controls were enrolled in this study. T cell proliferation in response to PHA was measured using Methyl Thiazol Tetrazolium test. ANA and ACA were measured by indirect immunofluorescence. CIC concentration was determined using poly ethylene glycol precipitation assay. Mean PHA response was 1.96 +/- 0.83 in patients and 3.72 +/- 1.39 in healthy controls (p< 0.001). ANA and CIC concentrations were not significantly different between two groups. In addition, ACA was detected only in patients. Increased production of ACA together with lower T cell response to mitogens in our patients provides evidence for the involvement of autoimmune mechanisms in the pathogenesis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | Stat Med 2009 Feb 28: 642-58 |
| PMID | 19065625 |
| Title | Working-correlation-structure identification in generalized estimating equations. |
| Abstract | Selecting an appropriate working correlation structure is pertinent to clustered data analysis using generalized estimating equations (GEE) because an inappropriate choice will lead to inefficient parameter estimation. We investigate the well-known criterion of QIC for selecting a working correlation structure, and have found that performance of the QIC is deteriorated by a term that is theoretically independent of the correlation structures but has to be estimated with an error. This leads us to propose a correlation information criterion (CIC) that substantially improves the QIC performance. Extensive simulation studies indicate that the CIC has remarkable improvement in selecting the correct correlation structures. We also illustrate our findings using a data set from the Madras Longitudinal schizophrenia Study. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | BMC Clin Pathol 2011 -1 11: 10 |
| PMID | 21867543 |
| Title | Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia. |
| Abstract | Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls. We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Virol. J. 2014 -1 11: 161 |
| PMID | 25186971 |
| Title | Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran. |
| Abstract | Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability. This first report from the Middle East aimed to determine BDV infection prevalence in Iranian acute psychiatric disorder patients and healthy controls through circulating immune complexes (CIC), antibodies (Ab) and antigen (pAg) in blood plasma using a standardized triple enzyme immune assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood donors, and 131 healthy controls) were assayed and data analyzed quantitatively and qualitatively. CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5% controls; 33.3% blood donors). In psychiatric patients CIC prevalence was higher than in controls (40.4%) and significantly correlating with bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR = 1.65). CIC values were significantly elevated in bipolar (p = 0.001) and major depressive disorder (p = 0.029) patients as compared to controls, and in females compared to males (p = 0.031). This study supports a similarly high prevalence of subclinical human BDV infections in Iran as reported for central Europe, and provides again an indication for the correlation of BDV infection and mood disorders. Further studies should address the morbidity risk for healthy carriers and those with elevated CIC levels, along with gender disparities. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Stat Med 2016 May 35: 1819-33 |
| PMID | 26626276 |
| Title | A determinant-based criterion for working correlation structure selection in generalized estimating equations. |
| Abstract | In generalized estimating equations (GEE), the correlation between the repeated observations on a subject is specified with a working correlation matrix. Correct specification of the working correlation structure ensures efficient estimators of the regression coefficients. Among the criteria used, in practice, for selecting working correlation structure, Rotnitzky-Jewell, Quasi Information Criterion (QIC) and Correlation Information Criterion (CIC) are based on the fact that if the assumed working correlation structure is correct then the model-based (naive) and the sandwich (robust) covariance estimators of the regression coefficient estimators should be close to each other. The sandwich covariance estimator, used in defining the Rotnitzky-Jewell, QIC and CIC criteria, is biased downward and has a larger variability than the corresponding model-based covariance estimator. Motivated by this fact, a new criterion is proposed in this paper based on the bias-corrected sandwich covariance estimator for selecting an appropriate working correlation structure in GEE. A comparison of the proposed and the competing criteria is shown using simulation studies with correlated binary responses. The results revealed that the proposed criterion generally performs better than the competing criteria. An example of selecting the appropriate working correlation structure has also been shown using the data from Madras schizophrenia Study. Copyright © 2015 John Wiley & Sons, Ltd. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |