Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Foo, J.C.; Streit, F.; Frank, J.; Witt, S.H.; Treutlein, J.; Baune, B.T.; ... ; Major Depressive Disorder Worki (2019)

Article / Letter to editor

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 assign-
ment 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 sum-
mary 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, R2 = 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 indi-
cate 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.

• depression
• electroconvulsive therapy
• major depression
• polygenic risk scores
• treatment-resistance

• All authors: Foo, J.C.; Streit, F.; Frank, J.; Witt, S.H.; Treutlein, J.; Baune, B.T.; Moebus, S.; Jockel, K.H.; Forstner, A.J.; Nothen, M.M.; Rietschel, M.; Sartorius, A.; Kranaster, L.; Wray, N.R.; Ripke, S.; Mattheisen, M.; Trzaskowski, M.; Byrne, E.M.; Abdellaoui, A.; Adams, M.J.; Agerbo, E.; Air, T.M.; Andlauer, T.F.M.; Bacanu, S.A.; Baekvad-Hansen, M.; Beekman, A.T.F.; Bigdeli, T.B.; Binder, E.B.; Blackwood, D.H.R.; Bryois, J.; Buttenschon, H.N.; Bybjerg-Grauholm, J.; Cai, N.; Castelao, E.; Christensen, J.H.; Clarke, T.K.; Coleman, J.R.I.; Colodro-Conde, L.; Couvy-Duchesne, B.; Craddock, N.; Crawford, G.E.; Davies, G.; Deary, I.J.; Degenhardt, F.; Derks, E.M.; Direk, N.; Dolan, C.V.; Dunn, E.C.; Eley, T.C.; Escott-Price, V.; Kiadeh, F.F.H.; Finucane, H.K.; Gaspar, H.A.; Gill, M.; Goes, F.S.; Gordon, S.D.; Grove, J.; Hall, L.S.; Hansen, C.S.; Hansen, T.F.; Herms, S.; Hickie, I.B.; Hoffmann, P.; Homuth, G.; Horn, C.; Hottenga, J.J.; Hougaard, D.M.; Ising, M.; Jansen, R.; Jones, I.; Jones, L.A.; Jorgenson, E.; Knowles, J.A.; Kohane, I.S.; Kraft, J.; Kretzschmar, W.W.; Krogh, J.; Kutalik, Z.; Li, Y.H.; Lind, P.A.; MacIntyre, D.J.; MacKinnon, D.F.; Maier, R.M.; Maier, W.; Marchini, J.; Mbarek, H.; McGrath, P.; McGuffin, P.; Medland, S.E.; Mehta, D.; Middeldorp, C.M.; Mihailov, E.; Milaneschi, Y.; Milani, L.; Mondimore, F.M.; Montgomery, G.W.; Mostafavi, S.; Mullins, N.; Nauck, M.; Ng, B.; Nivard, M.G.; Nyholt, D.R.; O'Reilly, P.F.; Oskarsson, H.; Owen, M.J.; Painter, J.N.; Pedersen, C.B.; Pedersen, M.G.; Peterson, R.E.; Pettersson, E.; Peyrot, W.J.; Pistis, G.; Posthuma, D.; Quiroz, J.A.; Qvist, P.; Rice, J.P.; Riley, B.P.; Rivera, M.; Mirza, S.S.; Schoevers, R.; Schulte, E.C.; Shen, L.; Shi, J.X.; Shyn, S.I.; Sigurdsson, E.; Sinnamon, G.C.B.; Smit, J.H.; Smith, D.J.; Stefansson, H.; Steinberg, S.; Strohmaier, J.; Tansey, K.E.; Teismann, H.; Teumer, A.; Thompson, W.; Thomson, P.A.; Thorgeirsson, T.E.; Traylor, M.; Trubetskoy, V.; Uitterlinden, A.G.; Umbricht, D.; Auwera, S. van der; Hemert, A.M. van; Viktorin, A.; Visscher, P.M.; Wang, Y.; Webb, B.T.; Weinsheimer, S.M.; Wellmann, J.; Willemsen, G.; Wu, Y.; Xi, H.L.S.; Yang, J.; Zhang, F.T.; Arolt, V.; Berger, K.; Boomsma, D.I.; Cichon, S.; Dannlowski, U.; Geus, E.J.C. de; DePaulo, J.R.; Domenici, E.; Domschke, K.; Esko, T.; Grabe, H.J.; Hamilton, S.P.; Hayward, C.; Heath, A.C.; Kendler, K.S.; Kloiber, S.; Lewis, G.; Li, Q.Q.S.; Lucae, S.; Madden, P.A.F.; Magnusson, P.K.; Martin, N.G.; McIntosh, A.M.; Metspalu, A.; Mors, O.; Mortensen, P.B.; Muller-Myhsok, B.; Nordentoft, M.; O'Donovan, M.C.; Paciga, S.A.; Pedersen, N.L.; Penninx, B.W.J.H.; Perlis, R.H.; Porteous, D.J.; Potash, J.B.; Preisig, M.; Schaefer, C.; Schulze, T.G.; Smoller, J.W.; Stefansson, K.; Tiemeier, H.; Uher, R.; Voelzke, H.; Weissman, M.M.; Werge, T.; Lewis, C.M.; Levinson, D.F.; Breen, G.; Borglum, A.D.; Sullivan, P.F.; Major Depressive Disorder Worki
• Date: 2019-01-31
• Journal: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
• Volume: 180
• Issue: 1
• Pages: 35 - 45
• DOI: doi:10.1002/ajmg.b.32700
• Link: https://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.32700