title: Biological tests for major depressive disorder that involve leukocyte gene expression assays.
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, ARHGAP24, 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.
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, University of Tokushima School of Medicine, Tokushima 770-8503, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Watanabe
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, University of Tokushima School of Medicine, Tokushima 770-8503, Japan. Electronic address: igajunichi@hotmail.com.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Iga
authors.affiliation: Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Saiwai, Fuchu, Tokyo, 183-8509, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, University of Tokushima School of Medicine, Tokushima 770-8503, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Numata
authors.affiliation: Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimodera
authors.affiliation: Department of Neuropsychiatry, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Psychiatry, Course of Integrated Brain Sciences, University of Tokushima School of Medicine, Tokushima 770-8503, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohmori
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D016002:Discriminant Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000097:blood; D012680:Sensitivity and Specificity
chemical_list: D012333:RNA, Messenger
keywords: Biomarker; Diagnostic test; Healthy subjects; Leukocyte gene expression; Major depressive disorder; PCR array