title: Stimulated gene expression profiles as a blood marker of major depressive disorder.
abstract: BACKGROUND
  Major depressive disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available.
  
  
  METHODS
  We used a classifier approach on blood gene expression profiles of a unique set of unmedicated subjects (MDD patients and control subjects) to select genes with expression predictive for disease status. To reveal blood gene expression changes related to major depressive disorder-disease, we applied a powerful ex vivo stimulus to the blood: incubation with lipopolysaccharide (LPS; 10 ng/mL blood).
  
  
  RESULTS
  Based on LPS-stimulated blood gene expression using whole-genome microarrays (primary cohort; 21 MDD patients, 21 healthy control subjects), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated using an independent quantitative polymerase chain reaction method (primary cohort, p = .007). The difference between depressive patients and control subjects was confirmed (p = .019) in a replication cohort of 13 MDD patients and 14 control subjects. The MDD signature score comprised expression levels of seven genes could discriminate depressive patients from control subjects with sensitivity of 76.9% and specificity of 71.8%.
  
  
  CONCLUSIONS
  We have shown for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of major depressive disorder.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands. sabine.spijker@cncr.vu.nl
authors.forename: Sabine
authors.initials: S
authors.lastname: Spijker
authors.forename: Jeroen S
authors.initials: JS
authors.lastname: Van Zanten
authors.forename: Simone
authors.initials: S
authors.lastname: De Jong
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.forename: Richard
authors.initials: R
authors.lastname: van Dyck
authors.forename: Frans G
authors.initials: FG
authors.lastname: Zitman
authors.forename: Jan H
authors.initials: JH
authors.lastname: Smit
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Witte J G
authors.initials: WJ
authors.lastname: Hoogendijk
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric