Citalopram-induced pathways regulation and tentative treatment-outcome-predicting biomarkers in lymphoblastoid cell lines from depression patients.

摘要: Antidepressant therapy is still associated with delays in symptomatic improvement and low response rates. Incomplete understanding of molecular mechanisms underlying antidepressant effects hampered the identification objective biomarkers for response. In this work, we studied transcriptome-wide expression followed by pathway analysis lymphoblastoid cell lines (LCLs) derived from 17 patients documented to SSRI antidepressants Munich Response Signatures (MARS) study upon short-term incubation (24 48 h) citalopram. Candidate transcripts were further validated qPCR MARS LCLs responders (n = 33) vs. non-responders (n = 36) afterward an independent cohort treatment-resistant (n = 20) first-line (n = 24) STAR*D study. observed significant associations GAD1 (glutamate decarboxylase 1; p = 0.045), TBC1D9 (TBC1 Domain Family Member 9; p = 0.014–0.021) NFIB (nuclear factor I B; p = 0.015–0.025) status, remission status depression scale, respectively. Pathway citalopram-altered gene indicated response-status-dependent transcriptional reactions. Whereas clinical neural function pathways primarily up- or downregulated after citalopram, deregulated mainly involved adhesion immune Results showed a marginal association (p = 0.068) but not (p = 0.23) (p = 0.27). Our results propose existence distinct regulation suggest GAD1, TBC1D9, as tentative predictors response, full remission, respectively, only weak overlap different outcome phenotypes.