title: RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response.
abstract: Response to antidepressant treatment is highly variable with some patients responding within a few weeks, whereas others have to wait for months until the onset of clinical effects. Gene expression profiling may be a tool to identify markers of antidepressant treatment response and new potential drug targets. In a first step, we selected 12 male, age- and severity-matched pairs of remitters and nonresponders, and analyzed expression profiles in peripheral blood at admission and after 2 and 5 weeks of treatment using Illumina expression arrays. We identified 127 transcripts significantly associated with treatment response with a minimal P-value of 9.41 × 10(-)(4) (false discovery rate-corrected). Analysis of selected transcripts in an independent replication sample of 142 depressed inpatients confirmed that lower expression of retinoid-related orphan receptor alpha (RORa, P=6.23 × 10(-4)), germinal center expressed transcript 2 (GCET2, P=2.08 × 10(-2)) and chitinase 3-like protein 2 (CHI3L2, P=4.45 × 10(-2)) on admission were associated with beneficial treatment response. In addition, leukocyte-specific protein 1 (LSP1) significantly decreased after 5 weeks of treatment in responders (P=2.91 × 10(-2)). Additional genetic, in vivo stress responsitivity data and murine gene expression findings corroborate our finding of RORa as a transcriptional marker of antidepressant response. In summary, using a genome-wide transcriptomics approach and subsequent validation studies, we identified several transcripts including the circadian gene transcript RORa that may serve as biomarkers indicating antidepressant treatment response.
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Hennings
authors.affiliation: Core Unit Biobanking and Molecular Biology, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Uhr
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Klengel
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Weber
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Pütz
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Touma
authors.affiliation: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Czamara
authors.affiliation: Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ising
authors.affiliation: Emeritus scientific member, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
authors.affiliation: Department of Clinical Research, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Lucae
mesh_terms: D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D005819:Genetic Markers; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012313:RNA
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