Classical pathway complement activity in schizophrenia. Neurosci Lett

Department of Biochemistry, University of Oxford, Oxford, England, United Kingdom
Neuroscience Letters (Impact Factor: 2.03). 03/2005; 374(1):35-7. DOI: 10.1016/j.neulet.2004.10.024
Source: PubMed


There is considerable evidence to suggest a role for complement in the pathogenesis of schizophrenia, but the data related to the classical pathway complement activity in patients with schizophrenia are conflicting. In the present study, the total hemolytic activity of the complement and the activities of individual complement components, C1, C2, C3 and C4, were determined in the blood serum of schizophrenic patients with positive family history of the disease and healthy subjects. In comparison to the healthy subjects, the mean values of the hemolytic activities of the C1, C3 and C4 complement components in the serum of the schizophrenic patients were significantly higher, and the mean value of the hemolytic activity of the C2 complement component was significantly lower. However, no significant difference was found between the mean values of the total hemolytic activity of complement in schizophrenic patients and healthy subjects. The C3 hemolytic activity was 2.17 times higher in medicated patients than in drug-free patients. Within each group examined no significant difference was found between smokers and non-smokers or between males and females. The results of this study suggest that the pathogenesis of schizophrenia is associated with alterations in activities of complement classical pathway components.

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    • "Complement is an integral part of the human immune system that serves to protecting the body against the invasion and proliferation of various microorganisms [24]. Accordingly, some researchers have speculated that deficiencies in the complement classical pathway may be involved in the autoimmune pathomechanisms and aberrant programmed cell death that possibly contribute to progression of schizophrenia [5]. Within the complement system, the complement protein C4 is a non-enzymatic component that is proteolytically activated when complement is activated via the classical or lectin activation pathways. "
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    ABSTRACT: Epidemiological studies have indicated that both maternal bacterial and viral infections during pregnancy increase the risk of schizophrenia among offspring, but to date there is not clear explanation for this increased risk. Previously, the decreased C4b-binding protein (C4BP), a potent circulating soluble inhibitor of the classical and lectin pathways of complement, was reported to be associated with risk of schizophrenia. Here, we analyzed 4 common single nucleotide polymorphisms (SNPs) of C4BPB and 5 SNPs of C4BPA in a group of 556 schizophrenia patients and a matched group of 610 healthy controls to see if the genes C4BPB and C4BPA, which encode C4BP, may confer a susceptibility to schizophrenia. Comparing the genotype and allele frequencies of those SNPs between cases and controls, we found no association between the C4BPB/C4BPA variants and schizophrenia. Our results provided preliminary evidence that C4BPB/C4BPA may not confer susceptibility to schizophrenia among Han Chinese. Further genetic studies from large-scale population are required to obtain more conclusive results. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 02/2015; 590. DOI:10.1016/j.neulet.2015.02.005 · 2.03 Impact Factor
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    • "Locally produced complement components in the CNS may have additional roles besides their direct immunological functions. Recent studies have suggested that complement may participate in normal developmental processes, such as pruning of synapses [11] and other developmental and degenerative processes [9,12], implicating it in diseases such as schizophrenia [13,14], Alzheimer disease [15], Parkinson disease [16], and glaucoma [17]. "
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    ABSTRACT: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo. Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were subjected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and complement factor H (CFH) immunoblotting. mRNA levels of complement genes and C1q protein levels in Muller cell cultures remained the same for all pressure levels after exposure for either 24 or 72 h. In primate and murine organotypic cultures, pressure elevation did not produce changes in complement gene expression or C1q and CFH protein levels at either the 24-h or 72-h time points. Pressure-related glial fibrillary acidic protein (GFAP) mRNA expression changes were detected in primate retinal organotypic cultures (analysis of variance [ANOVA]; p<0.05). mRNA expression of several other genes changed as a result of time in culture. Eyes subjected to microbead-induced IOP elevation had no differences in mRNA expression of complement genes and C1q protein levels (ANOVA; p>0.05 for both) with contralateral control and naïve control eyes. Short-term elevation of pressure in vitro as well as short-term (1 week) IOP elevation in vivo does not seem to dramatically alter complement system gene expression in the retina. Prolonged expression to elevated pressure may be necessary to affect the complement system expression.
    Molecular vision 01/2014; 20:140-52. · 1.99 Impact Factor
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    • "Our recent studies indicate the crucial role of the immune system in schizophrenia and provide evidence on the alterations in the major mediator of the immune response, the complement system, in pathogenesis of this disorder [6-13]. In particular, increased functional activities of the complement classical pathway and C1Q protein, the initiator of the complement classical cascade, in schizophrenia-affected subjects has been found [8,10]. These findings are of special interest accounting for a positive linkage of schizophrenia with chromosome 1p36 loci located nearby C1QA and C1QB genes (1p36.12) "
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    ABSTRACT: Schizophrenia is a complex, multifactorial psychiatric disorder. Our previous findings indicated that altered functional activity of the complement system, a major mediator of the immune response, is implicated in the pathogenesis of schizophrenia. In order to explore whether these alterations are genetically determined or not, in the present study we evaluated the possible association of complement C1Q component gene variants with susceptibility to schizophrenia in Armenian population, focusing on four frequent single nucleotide polymorphisms (SNPs) of C1QA and C1QB genes. In the present study four SNPs of the complement C1Q component genes (C1QA: rs292001, C1QB rs291982, rs631090, rs913243) were investigated in schizophrenia-affected and healthy subjects. Unrelated Caucasian individuals of Armenian nationality, 225 schizophrenic patients and the same number of age- and sex-matched healthy subjects, were genotyped. Genotyping was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP) and quantitative real-time (qRT) PCR methods. While there was no association between C1QA rs292001, C1QB rs913243 and rs631090 genetic variants and schizophrenia, the C1QB rs291982*G minor allele was significantly overrepresented in schizophrenic patients (G allele frequency 58%) when compared to healthy subjects (46%, OR = 1.64, p(corr) = 0.0008). Importantly, the susceptibility for schizophrenia was particularly associated with C1QB rs291982 GG genotype (OR = 2.5, p(corrected) = 9.6E-5). The results obtained suggest that C1QB gene may be considered as a relevant candidate gene for susceptibility to schizophrenia, and its rs291982*G minor allele might represent a risk factor for schizophrenia at least in Armenian population. Replication in other centers/populations is necessary to verify this conclusion.
    BMC Medical Genetics 09/2011; 12(1):126. DOI:10.1186/1471-2350-12-126 · 2.08 Impact Factor
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