| 1 | World J. Biol. Psychiatry 2008 -1 9: 225-30 |
|---|---|
| PMID | 17853297 |
| Title | Complement C4B protein in schizophrenia. |
| Abstract | Partial and/or complete deficiency of the complement protein C4 is associated with autoimmune and infectious diseases. Infectious or autoimmune processes may have a role in schizophrenia. Previous reports suggest abnormalities in the complement C4B isotype in schizophrenia and other mental disorders. We assessed C4A and C4B isotypes and serum C4B protein concentration in Armenian schizophrenic patients. Although there was no difference in frequency of C4BQ0, C4B serum protein level was significantly decreased in the schizophrenic patients compared with healthy controls. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | World J. Biol. Psychiatry 2008 -1 9: 225-30 |
| PMID | 17853297 |
| Title | Complement C4B protein in schizophrenia. |
| Abstract | Partial and/or complete deficiency of the complement protein C4 is associated with autoimmune and infectious diseases. Infectious or autoimmune processes may have a role in schizophrenia. Previous reports suggest abnormalities in the complement C4B isotype in schizophrenia and other mental disorders. We assessed C4A and C4B isotypes and serum C4B protein concentration in Armenian schizophrenic patients. Although there was no difference in frequency of C4BQ0, C4B serum protein level was significantly decreased in the schizophrenic patients compared with healthy controls. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | J. Hum. Genet. 2010 May 55: 285-92 |
| PMID | 20339380 |
| Title | An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes. |
| Abstract | schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Proteomics Clin Appl 2015 Oct 9: 907-16 |
| PMID | 25821032 |
| Title | Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. |
| Abstract | Previous studies have shown that blood serum phosphoproteins are altered in schizophrenia patients in comparison to controls. However, it is not known whether phosphoproteins are also changed in response to treatment with antipsychotics. Blood samples were taken from patients (n = 23) at baseline and after 6 weeks of olanzapine treatment. Immobilized metal ion affinity chromatography (IMAC) was used for enrichment of serum phosphoproteins and these were analyzed by label-free LC-MS in expression mode (LC-MS(E) ). We identified 11 proteins that were changed significantly in overall abundance and 45 proteins that showed changes in phosphorylation after the antipsychotic treatment. The altered phosphoproteins were mainly involved in the acute phase response, lipid and glucose homeostasis (LXR), retinoic acid signaling (RXR), and complement pathways. Some of the proteins showed a marked increase in phosphorylation, including apolipoprotein A-I (3.4-fold), alpha-1-anti-chymotrypsin (3.1-fold), and apolipoprotein B-100 (2.2-fold). In addition, several proteins showed either decreased phosphorylation (e.g. complement C4A, collagen alpha-1 chain, complement factor H) or a mixture of increased and decreased phoshphorylation (e.g. afamin, complement C5, complement factor B). Finally, 24 of the altered phosphoproteins showed opposite directional changes in a comparison of baseline schizophrenia patients before and after treatment with olanzapine. These included alpha-1B-glycoprotein, apolipoprotein A-IV, vitamin D-binding protein, and prothrombin. These data demonstrate the potential for future studies of serum phosphoproteins as a readout of physiological function and might have utility in studies aimed at identification of biomarkers for drug response prediction or monitoring. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Nature 2016 Feb 530: 177-83 |
| PMID | 26814963 |
| Title | Schizophrenia risk from complex variation of complement component 4. |
| Abstract | schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |