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

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 (FDR-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.

This study was supported by DFG (EXC 1010 SyNergy), BMBF (01ES0811)

References

[1] Hennings et al., Transl Psychiatry 2015; e538