| 1 | Proc. Natl. Acad. Sci. U.S.A. 2005 Oct 102: 15533-8 |
|---|---|
| PMID | 16223876 |
| Title | Comparative gene expression analysis of blood and brain provides concurrent validation of SELENBP1 up-regulation in schizophrenia. |
| Abstract | Microarray techniques hold great promise for identifying risk factors for schizophrenia (SZ) but have not yet generated widely reproducible results due to methodological differences between studies and the high risk of type I inferential errors. Here we established a protocol for conservative analysis and interpretation of gene expression data from the dorsolateral prefrontal cortex of SZ patients using statistical and bioinformatic methods that limit false positives. We also compared brain gene expression profiles with those from peripheral blood cells of a separate sample of SZ patients to identify disease-associated genes that generalize across tissues and populations and further substantiate the use of gene expression profiling of blood for detecting valid SZ biomarkers. Implementing this systematic approach, we: (i) discovered 177 putative SZ risk genes in brain, 28 of which map to linked chromosomal loci; (ii) delineated six biological processes and 12 molecular functions that may be particularly disrupted in the illness; (iii) identified 123 putative SZ biomarkers in blood, 6 of which (BTG1, GSK3A, HLA-DRB1, HNRPA3, SELENBP1, and SFRS1) had corresponding differential expression in brain; (iv) verified the differential expression of the strongest candidate SZ biomarker (SELENBP1) in blood; and (v) demonstrated neuronal and glial expression of SELENBP1 protein in brain. The continued application of this approach in other brain regions and populations should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for SZ. The identification of valid peripheral biomarkers for SZ may ultimately facilitate early identification, intervention, and prevention efforts as well. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | J Psychiatr Res 2008 Jul 42: 639-43 |
| 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 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Sep 147B: 686-9 |
| PMID | 18163446 |
| Title | The utility of SELENBP1 gene expression as a biomarker for major psychotic disorders: replication in schizophrenia and extension to bipolar disorder with psychosis. |
| Abstract | While microarray studies are generating novel insights into the etiology of major psychiatric disorders, the validation of microarray-identified candidate genes and their role in the causality of these disorders has been less often studied. We have previously demonstrated, by microarray, up-regulation of SELENBP1 in the brain and blood of patients with schizophrenia. The main aim of the current study was to validate this finding using quantitative real-time PCR (QPCR) in an independent brain cohort that included patients with bipolar disorder. Our sample consisted of mRNAs from the dorsolateral prefrontal cortex (dlPFC) of 34 schizophrenic patients, 33 bipolar disorder patients (including 20 with psychotic history), and 34 normal control subjects. QPCR was employed to assess gene expression changes, with C(T) values analyzed using an ANCOVA approach. The results demonstrated that SELENBP1 mRNA was upregulated in schizophrenic brains versus controls (P = 0.046) and, in addition, that SELENBP1 gene expression was strongly positively correlated with presence of psychosis across diagnoses (P < 0.001, increased by 12%). Based on these findings, we conclude that elevated SELENBP1 is a possibly consistent feature in the schizophrenic brain and that this finding could underlie some commonalities of psychosis across the boundaries of diagnoses. Future studies should exploit DNA-based methods and molecular investigations on the role of SELENBP1 in order to gain insights into the nature of its influence on schizophrenia and psychotic symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Sep 147B: 686-9 |
| PMID | 18163446 |
| Title | The utility of SELENBP1 gene expression as a biomarker for major psychotic disorders: replication in schizophrenia and extension to bipolar disorder with psychosis. |
| Abstract | While microarray studies are generating novel insights into the etiology of major psychiatric disorders, the validation of microarray-identified candidate genes and their role in the causality of these disorders has been less often studied. We have previously demonstrated, by microarray, up-regulation of SELENBP1 in the brain and blood of patients with schizophrenia. The main aim of the current study was to validate this finding using quantitative real-time PCR (QPCR) in an independent brain cohort that included patients with bipolar disorder. Our sample consisted of mRNAs from the dorsolateral prefrontal cortex (dlPFC) of 34 schizophrenic patients, 33 bipolar disorder patients (including 20 with psychotic history), and 34 normal control subjects. QPCR was employed to assess gene expression changes, with C(T) values analyzed using an ANCOVA approach. The results demonstrated that SELENBP1 mRNA was upregulated in schizophrenic brains versus controls (P = 0.046) and, in addition, that SELENBP1 gene expression was strongly positively correlated with presence of psychosis across diagnoses (P < 0.001, increased by 12%). Based on these findings, we conclude that elevated SELENBP1 is a possibly consistent feature in the schizophrenic brain and that this finding could underlie some commonalities of psychosis across the boundaries of diagnoses. Future studies should exploit DNA-based methods and molecular investigations on the role of SELENBP1 in order to gain insights into the nature of its influence on schizophrenia and psychotic symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Schizophr. Res. 2009 Sep 113: 268-72 |
| PMID | 19596560 |
| Title | Family-based association study of SELENBP1 in schizophrenia. |
| Abstract | The SELENBP1 gene previously was found to be up-regulated in microarray analysis of both peripheral blood cell and brain tissue samples from schizophrenia patients. Quantitative PCR analysis subsequently corroborated the altered expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley Array Correction. The aim of this study was to extend those findings by employing family-based association methods to a sample of over 2400 individuals (including 1214 individuals affected by schizophrenia) of Han Chinese descent living in Taiwan. One of four haplotype-tagging SNPs and two different two-marker haplotypes showed nominally significant evidence for association with schizophrenia under an additive model, suggesting that genetic variation in SELENBP1 may influence risk for the disorder, while this significance did not remain when other inheritance models were considered. Further comprehensive analysis with other SNPs and haplotypes is needed and warranted. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Behav Brain Funct 2010 -1 6: 40 |
| PMID | 20615253 |
| Title | Copy number variation of the SELENBP1 gene in schizophrenia. |
| Abstract | schizophrenia is associated with rare copy-number (CN) mutations. Screening for such alleles genome-wide, though comprehensive, cannot study in-depth the causality of particular loci, therefore cannot provide the functional interpretation for the disease etiology. We hypothesized that CN mutations in the SELENBP1 locus could associate with the disorder and that these mutations could alter the gene product's activity in patients. We analyzed SELENBP1 CN variation (CNV) in blood DNA from 49 schizophrenia patients and 49 controls (cohort A). Since CN of genes may vary among tissues, we investigated SELENBP1 CN in age- sex- and postmortem interval-matched cerebellar DNA samples from 14 patients and 14 controls (cohort B). Since CNV may either be de-novo or inherited we analyzed CNV of the SELENBP1 locus in blood DNA from 26 trios of schizophrenia probands and their healthy parents (cohort C). SELENBP1 mRNA levels were measured by real-time PCR. In cohort A reduced CN of the SELENBP1 locus was found in four patients but in none of the controls. In cohort B we found reduced CN of the SELENBP1 locus in two patients but in none of the controls. In cohort C three patients exhibited drastic CN reduction, not present in their parents, indicating de-novo mutation. A reduction in SELENBP1 mRNA levels in the postmortem cerebellar samples of schizophrenia patients was found. We report a focused study of CN mutations in the selenium binding-protein1 (SELENBP1) locus previously linked with schizophrenia. We provide evidence for recurrence of decreased CN of the SELENBP1 locus in three unrelated patients' cohorts but not in controls, raising the possibility of functional involvement of these mutations in the etiology of the disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Transl Psychiatry 2015 -1 5: e615 |
| PMID | 26241353 |
| Title | SELENBP1 expression in the prefrontal cortex of subjects with schizophrenia. |
| Abstract | Selenium binding protein 1 (SELENBP1) messenger RNA (mRNA) has previously been shown to be upregulated in the brain and blood from subjects with schizophrenia. We aimed to validate these findings in a new cohort using real-time PCR in Brodmann's Area (BA) 9, and to determine the disease specificity of increased SELENBP1 expression by measuring SELENBP1 mRNA in subjects with major depressive disorder and bipolar disorder. We then extended the study to include other cortical regions such as BA8 and BA44. SELENBP1 mRNA was higher in BA9 (P = 0.001), BA8 (P = 0.003) and BA44 (P = 0.0007) from subjects with schizophrenia. Conversely, in affective disorders, there was no significant difference in SELENBP1 mRNA in BA9 (P = 0.67), suggesting that the upregulation may be diagnosis specific. Measurement of SELENBP1 protein levels showed that changes in mRNA did not translate to changes in protein. In addition, chronic treatment of rats with antipsychotics did not significantly affect the expression of SELENBP1 in the cortex (P = 0.24). Our data show that elevated SELENBP1 transcript expression is widespread throughout the prefrontal cortex in schizophrenia, and confirm that this change is a consistent feature of schizophrenia and not a simple drug effect. |
| SCZ Keywords | schizophrenia, schizophrenic |