Abstract

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease-related common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD-PRS were calculated for these inpatients and a separate population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD-working group (Cases: n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R-2 = 1.173%); patients showed higher MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.

Authors	Foo, Jerome C.; Streit, Fabian; Frank, Josef; Witt, Stephanie H.; Treutlein, Jens; Baune, Bernhard T.; Moebus, Susanne; Joeckel, Karl-Heinz; Forstner, Andreas J.; Noethen, Markus M.; Rietschel, Marcella; Sartorius, Alexander; Kranaster, Laura; Wray, Naomi R.; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M.; Abdellaoui, Abdel; Adams, Mark J.; Agerbo, Esben; Air, Tracy M.; Andlauer, Till F. M.; Bacanu, Silviu-Alin; Baekvad-Hansen, Marie; Beekman, Aartjan T. F.; Bigdeli, Tim B.; Binder, Elisabeth B.; Blackwood, Douglas H. R.; Bryois, Julien; Buttenschon, Henriette N.; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan R. I.; Colodro-Conde, Lucia; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E.; Davies, Gail; Deary, Ian J.; Degenhardt, Franziska; Derks, Eske M.; Direk, Nese; Dolan, Conor V.; Dunn, Erin C.; Eley, Thalia C.; Escott-Price, Valentina; Kiadeh, Farnush Farhadi Hassan; Finucane, Hilary K.; Gaspar, Helena A.; Gill, Michael; Goes, Fernando S.; Gordon, Scott D.; Grove, Jakob; Hall, Lynsey S.; Hansen, Christine Soholm; Hansen, Thomas F.; Herms, Stefan; Hickie, Ian B.; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M.; Ising, Marcus; Jansen, Rick; Jones, Ian; Jones, Lisa A.; Jorgenson, Eric; Knowles, James A.; Kohane, Isaac S.; Kraft, Julia; Kretzschmar, Warren W.; Krogh, Jesper; Kutalik, Zoltan; Li, Yihan; Lind, Penelope A.; MacIntyre, Donald J.; MacKinnon, Dean F.; Maier, Robert M.; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E.; Mehta, Divya; Middeldorp, Christel M.; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mondimore, Francis M.; Montgomery, Grant W.; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G.; Nyholt, Dale R.; O'Reilly, Paul F.; Oskarsson, Hogni; Owen, Michael J.; Painter, Jodie N.; Pedersen, Carsten Bocker; Pedersen, Marianne Giortz; Peterson, Roseann E.; Pettersson, Erik; Peyrot, Wouter J.; Pistis, Giorgio; Posthuma, Danielle; Quiroz, Jorge A.; Qvist, Per; Rice, John P.; Riley, Brien P.; Rivera, Margarita; Mirza, Saira Saeed; Schoevers, Robert; Schulte, Eva C.; Shen, Ling; Shi, Jianxin; Shyn, Stanley I.; Sigurdsson, Engilbert; Sinnamon, Grant C. B.; Smit, Johannes H.; Smith, Daniel J.; Stefansson, Hreinn; Steinberg, Stacy; Strohmaier, Jana; Tansey, Katherine E.; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A.; Thorgeirsson, Thorgeir E.; Traylor, Matthew; Trubetskoy, Vassily; Uitterlinden, Andre G.; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M.; Viktorin, Alexander; Visscher, Peter M.; Wang, Yunpeng; Webb, Bradley T.; Weinsheimer, Shantel Marie; Wellmann, Jurgen; Willemsen, Gonneke; Wu, Yang; Xi, Hualin S.; Yang, Jian; Zhang, Futao; Arolt, Volker; Berger, Klaus; Boomsma, Dorret I.; Cichon, Sven; Dannlowski, Udo; de Geus, E. J. C.; DePaulo, J. Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tonu; Grabe, Hans J.; Hamilton, Steven P.; Hayward, Caroline; Heath, Andrew C.; Kendler, Kenneth S.; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S.; Lucae, Susanne; Madden, Pamela A. F.; Magnusson, Patrik K.; Martin, Nicholas G.; McIntosh, Andrew M.; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Mueller-Myhsok, Bertram; Nordentoft, Merete; O'Donovan, Michael C.; Paciga, Sara A.; Pedersen, Nancy L.; Penninx, Brenda W. J. H.; Perlis, Roy H.; Porteous, David J.; Potash, James B.; Preisig, Martin; Schaefer, Catherine; Schulze, Thomas G.; Smoller, Jordan W.; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Voelzke, Henry; Weissman, Myrna M.; Werge, Thomas; Lewis, Cathryn M.; Levinson, Douglas F.; Breen, Gerome; Borglum, Anders D.; Sullivan, Patrick F.
Journal	AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
Pages	35-45
Volume	180
Date	1/01/2019
Grant ID	U01 MH109528
Funding Body	National Institute of Mental Health
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1002/ajmg.b.32700
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