Biological tests for major depressive disorder that involve leukocyte gene expression assays
JOURNAL OF PSYCHIATRIC RESEARCH
Authors: Watanabe, Shin-ya; Iga, Jun-ichi; Ishii, Kazuo; Numata, Shusuke; Shimodera, Shinji; Fujita, Hirokazu; Ohmori, Tetsuro
Abstract
Background: Development of easy-to-use biological diagnostic tests for major depressive disorder (MDD) may facilitate MDD diagnosis and delivery of optimal treatment. Here, we examined leukocyte gene expression to develop a biological diagnostic test for MDD. Methods: 25 drug-naive MDD patients (MDDs) and 25 age- and sex-matched healthy subjects (Controls) participated in a pilot study. A subsequent replication study involved 20 MDDs and 18 Controls. We used custom-made PCR array plates to examine mRNA levels of 40 candidate genes in leukocyte samples to assess whether any combination of these genes could be used to differentiate MDDs from Controls based on expression profiles. Results: Among 40 candidate genes, we identified a set of seven genes (PDGFC, SLC6A4, PDLIM5, ARKGA P24, PRNP, HDAC5, and IL1R2), each of which had expression levels that differed significantly between MDD and Control samples in the pilot study. To identify genes whose expression best differentiated between MDDs and Controls, a linear discriminant function was developed to discriminate between MDDs and Controls based on the standardized values of gene expression after Z-score transformation. Ultimately, five genes (PDGFC, SLC6A4, ARHGAP24, PRNP, and HDAC5) were selected for a multi-assay diagnostic test. In the pilot study, this diagnostic test demonstrated sensitivity and specificity of 80% and 92%, respectively. The replication study yielded nearly identical results, sensitivity of 85% and specificity. of 89%. Conclusions: Using leukocyte gene expression profiles, we could differentiate MDDs from Controls with adequate sensitivity and specificity. Additional markers not yet identified might further improve the performance of this test. (C) 2015 Elsevier Ltd. All rights reserved.
Human Chorionic Gonadotropin Regulates Endothelial Cell Responsiveness to Interleukin 1 and Amplifies the Cytokine-Mediated Effect on Cell Proliferation, Migration and the Release of Angiogenic Factors
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Authors: Bourdiec, Amelie; Bedard, David; Rao, C. V.; Akoum, Ali
Abstract
Problem Successful embryonic implantation requires an appropriate communication network between the embryo and its near environment within the implantation site. Herein, we examined whether human chorionic gonadotropin (hCG), the major embryonic signal, targets endothelial cells and regulate their responsiveness to interleukin 1 (IL1), one of the earliest signals released by embryonic cells. Method of study Human microvascular endothelial cell proliferation and migration following exposure to various concentrations of hCG and/or IL1B for different time periods were analyzed by BrdU incorporation and wound healing assays. The expression of soluble (s) and membrane-bound (mb) IL1 receptors (IL1Rs), IL1R antagonist (IL1RN), luteinizing hormone/choriogonadotropin receptor (LHCGR), and IL8 was determined by real-time PCR, Western blot, and ELISA. Results Cell proliferation and migration increased in response to IL1B and further in the presence of hCG. IL1B up-regulated both the signaling IL1R1 and the inhibitory IL1R2, while adding hCG further increased IL1R1 and significantly downregulated IL1R2. This translated into an increased secretion of IL8, which was inhibited in cells where IL1R2 was overexpressed. Conclusions These findings reveal a new mechanism by which hCG may target endothelial cells to directly stimulate angiogenesis and favor embryonic growth.