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Transcriptomics and the mechanisms of antidepressant efficacy

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Karen Hodgson, Katherine E. Tansey, Timothy Powell, Giovanni Coppola, Rudolf Uher, Mojca Zvezdana Dernovšek, Ole Mors, Joanna Hauser, Daniel Souery, Wolfgang Maier, Neven Henigsberg, Marcella Rietschel, Anna Placentino, Katherine J. Aitchison, Ian W. Craig, Anne E. Farmer, Gerome Breen, Peter Mcguffin, Richard Dobson

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalEuropean Neuropsychopharmacology
Issue number1
Early online date12 Nov 2015
Accepted/In press20 Oct 2015
E-pub ahead of print12 Nov 2015
Published1 Jan 2016

King's Authors


The mechanisms by which antidepressants have their effects are not clear and the reasons for variability in treatment outcomes are also unknown. However, there is evidence from candidate gene research that indicates gene expression changes may be involved in antidepressant action. In this study, we examined antidepressant-induced alterations in gene expression on a transcriptome-wide scale, exploring associations with treatment response. Blood samples were taken from a subset of depressed patients from the GENDEP study (n=136) before and after eight weeks of treatment with either escitalopram or nortriptyline. Transcriptomic data were obtained from these samples using Illumina HumanHT-12 v4 Expression BeadChip microarrays. When analysing individual genes, we observed that changes in the expression of two genes (MMP28 and KXD1) were associated with better response to nortriptyline. Considering connectivity between genes, we identified modules of genes that were highly coexpressed. In the whole sample, changes in one of the ten identified coexpression modules showed significant correlation with treatment response (cor=0.27, p=0.0029). Using transcriptomic approaches, we have identified gene expression correlates of the therapeutic effects of antidepressants, highlighting possible molecular pathways involved in efficacious antidepressant treatment.

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