Transcriptomics and the mechanisms of antidepressant efficacy

Karen Hodgson; Katherine E. Tansey; Timothy R. 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

doi:10.1016/j.euroneuro.2015.10.009

Transcriptomics and the mechanisms of antidepressant efficacy

Karen Hodgson, Katherine E. Tansey, Timothy R. 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

Medicine

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	105-112
Number of pages	8
Journal	European Neuropsychopharmacology
Volume	26
Issue number	1
DOIs	https://doi.org/10.1016/j.euroneuro.2015.10.009
Publication status	Published - Jan 1 2016

Bibliographical note

Funding Information:
We acknowledge the contribution of the following collaborators: Helen Dean, Amanda Elkin, Joanna Gray, Cerisse Gunasinghe, Desmond Campbell, David Dempster, Richard J Williamson, Caterina Giovannini, Julien Mendlewicz, Thomas Schulze, Jana Strohmaier, Christine Schmäl, Susanne Höfels, Anna Schuhmacher, Ute Pfeiffer, Sandra Weber, Anne Schinkel Stamp, Piotr Czerski Alenka Tancic, Jerneja Sveticic, Zrnka Kovacic, Pawe Kapelski, Maria Skibinska, Aleksandra Rajewska, Aleksandra Szczepankiewicz and Elzbieta Cegielska. We specially acknowledge the contribution of Jorge Perez, who was the Principal Investigator at Brescia, Italy, and who passed away in October 2007, and the late Professor Andrej Marusic, who was the Lead Investigator at Ljubljana, and who passed away in June 2008.

Funding Information:
The GENDEP project was funded by the European Commission Framework 6 Grant, EC Contract Ref.: LSHB-CT-2003–503428. Lundbeck provided both nortriptyline and escitalopram free of charge for the GENDEP study. GlaxoSmithKline, the Medical Research Council, the Biomedical Research Centre for Mental Health at the Institute of Psychiatry and South London and Maudsley NHS Foundation Trust (funded by the United Kingdom National Institute for Health Research of the Department of Health) contributed to the funding of the sample collection at the Institute of Psychiatry, London, through add-on projects or latterly staff funding, including the MRC grant MR/L014815/1. Dr. Uher is supported by the Canada Research Chairs program ( http://www.chairs-chaires.gc.ca/ ). The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing the paper.

Publisher Copyright:
© 2015 Elsevier B.V. and ECNP.

ASJC Scopus Subject Areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.euroneuro.2015.10.009

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Hodgson, K., Tansey, K. E., Powell, T. R., Coppola, G., Uher, R., Zvezdana Dernovšek, M., Mors, O., Hauser, J., Souery, D., Maier, W., Henigsberg, N., Rietschel, M., Placentino, A., Aitchison, K. J., Craig, I. W., Farmer, A. E., Breen, G., McGuffin, P., & Dobson, R. (2016). Transcriptomics and the mechanisms of antidepressant efficacy. European Neuropsychopharmacology, 26(1), 105-112. https://doi.org/10.1016/j.euroneuro.2015.10.009

Hodgson, K, Tansey, KE, Powell, TR, Coppola, G, Uher, R, Zvezdana Dernovšek, M, Mors, O, Hauser, J, Souery, D, Maier, W, Henigsberg, N, Rietschel, M, Placentino, A, Aitchison, KJ, Craig, IW, Farmer, AE, Breen, G, McGuffin, P & Dobson, R 2016, 'Transcriptomics and the mechanisms of antidepressant efficacy', European Neuropsychopharmacology, vol. 26, no. 1, pp. 105-112. https://doi.org/10.1016/j.euroneuro.2015.10.009

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abstract = "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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AU - Mors, Ole

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AU - Souery, Daniel

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Transcriptomics and the mechanisms of antidepressant efficacy

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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