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RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response.

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Hennings,  J M
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Uhr,  M
Max Planck Institute of Psychiatry, Max Planck Society;

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Klengel,  T
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Weber,  P
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Pütz,  B
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Touma,  C
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Czamara,  D
Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society;

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Ising,  M
Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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Holsboer,  F
Emeritiertes wissenschaftliches Mitglied, Max Planck Institute of Psychiatry, Max Planck Society;

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Lucae,  S
Dept. Clinical Research, Max Planck Institute of Psychiatry, Max Planck Society;

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tp20159a.pdf
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Citation

Hennings, J. M., Uhr, M., Klengel, T., Weber, P., Pütz, B., Touma, C., et al. (2015). RNA expression profiling in depressed patients suggests retinoid-related orphan receptor alpha as a biomarker for antidepressant response. Translational psychiatry, 5: e538. doi:10.1038/tp.2015.9.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0029-207D-3
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.