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Zusammenfassung:
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.
