title: Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses.
abstract: Several microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients with MDD who were at least moderately ill and 14 healthy controls matched pairwise for age and sex. After filtering, we compared expression of entire probes between patients and controls and identified DEGs. The DEGs were evaluated by pathway and network analyses. For the candidate gene analysis, we utilized 169 previously prioritized genes and examined their case-control separation efficiency and correlational co-expression network in patients relative to controls. The 317 screened DEGs mapped to a significantly over-represented pathway, the "synaptic transmission" pathway. The protein-protein interaction network was also significantly enriched, in which a number of key molecules for depression were included. The co-expression network of candidate genes was markedly disrupted in patients. This study provided evidence for an altered molecular network along with several key molecules in MDD and confirmed that the candidate genes are worthwhile targets for depression research.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.|Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8553, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Daimei
authors.initials: D
authors.lastname: Sasayama
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: DNA Chip Research Inc., Kanagawa, 230-0045, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, 187-8553, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Kim
authors.affiliation: National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods; D003865:Major Depressive Disorder / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D010045:Outpatients; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D059467:Transcriptome
chemical_list: D015415:Biomarkers