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.

Understanding Heterogeneity in Supplementation Effects of Selenium in Men: A Study of Stratification Variables and Human Genetics in a Prospective Sample from New Zealand

“…However, Rayman et al [89] have found no evidence to support a positive effect of Se supplementation on mood and quality of life of an elderly population. The gene expression level of selenoprotein binding protein1 has been linked to major psychotic disorders [90]. Our analysis has shown that the GPX1 rs1050450 allele C positively interacts with mental illness and produces a significant association with peroxide induced DNA damage compared to that of the healthy controls both before after Se supplementation.…”

Human selenium binding protein-1 (hSP56) is a negative regulator of HIF-1α and suppresses the malignant characteristics of prostate cancer cells

“…Demethylating agents that can reverse the reduced hSP56 expression, consequently recovering the normal balance of HIF-1α and hSP56, may become interesting candidates for future chemopreventive drug development. Understanding the mechanisms by which hSP56 expression is regulated may become useful to understand the functions of hSP56 in other diseases, since SELENBP1 gene expression has been shown to be upregulated in major psychotic disorders such as schizophrenia (26, 27).…”

Blood mononuclear cell gene expression signature of postpartum depression

“…22,23 Some of the differentially expressed genes have been proposed to possess pathogenetic relevance. 24,25 Sampling surrogate mononuclear cells allows access to freshly isolated systemic cellular reactivity during a clinically relevant time window among carefully selected homogenous samples of patients. Most studies to date have measured peripheral blood mononuclear cell (PBMC) gene expression levels at baseline or in lymphoblastoid cell lines derived from chronic drug-treated patients, which may not grapple the full potential of this methodology.…”