| 1 | Schizophr. Res. 2004 Mar 67: 41-52 |
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| PMID | 14741323 |
| Title | Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. |
| Abstract | In order to help prioritize the selection of candidate genes and to study possible trait and not state related changes in gene expression, we compared lymphocytic gene expression patterns of five individual family members with schizophrenia and nine unaffected individuals from a large multiplex high density pedigree. We screened gene expression by microarray consisting of 1128 brain focused genes. Three criteria for selection of microarray gene differences between schizophrenia and unaffected family members were employed: a significant t-test, expression in a majority of subjects, and fold change magnitude. Gene expression levels were significantly different for nine genes between individuals with schizophrenia compared to unaffected controls, and two genes were validated by real-time PCR. The expression of the neuropeptide Y receptor Y1 gene (NPY1R localized at 4q31.3-q32) and the human guanine nucleotide-binding regulatory protein Go-alpha (GNAO1 localized at 16q13) was significantly decreased in individuals with schizophrenia compared to unaffected family controls by microarray and real-time PCR. The cytosolic malate dehydrogenase gene (MDH1 localized at 2p13.3) was also significantly increased by microarray analysis and showed a trend for increase by real-time PCR. The significant genes are discussed in terms of proximity to linkage regions, prior association studies of schizophrenia, and other reports of microarray screening of schizophrenia tissue. Evidence from these studies taken together with the present study suggests critical pathways in schizophrenia may be studied in peripheral tissue as part of the strategy in functional genomic convergence. This preliminary study needs to be repeated by screening a larger set of genes in additional families with schizophrenia. The present study offers support for examination of gene expression patterns using lymphocytic RNA for complex neuropsychiatric disorders from large cohorts of patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | J Psychiatr Res 2008 Jul 42: 639-43 |
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| PMID | 17825842 |
| Title | Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia. |
| Abstract | Recent studies reported gene expression alterations in peripheral blood cells (PBC) obtained from patients with schizophrenia as compared to healthy controls. These alterations can not only be regarded as potential biomarkers but can also further our understanding of the disease. In light of previous reports, expression levels of the following genes: APOBEC3B, CXCL1, DRD2, GNAO1, Kir2.3, S100A9, and SELENBP1 in PBCs were compared between 30 first-hospitalized patients with schizophrenia and 26 healthy controls using quantitative real-time PCR. A significant elevation (2.6-fold; p<0.05) was confirmed for transcripts from the gene CXCL1 but not from the other genes investigated. Within the patients group, APOBEC3B expression was inversely correlated with duration of neuroleptic treatment. These findings indicate that gene expression in PBC from patients with schizophrenia may not only vary with the methods used for analysis but also with state-related differences in gene expression. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | J. Hum. Genet. 2011 Jul 56: 478-83 |
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| PMID | 21512575 |
| Title | Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia. |
| Abstract | The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | J. Hum. Genet. 2011 Jul 56: 478-83 |
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| PMID | 21512575 |
| Title | Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia. |
| Abstract | The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. |
| SCZ Keywords | schizophrenia, schizophrenic |