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

Jerome C. Foo; Fabian Streit; Josef Frank; Jens Treutlein; Bernhard T. Baune; Susanne Moebus; Karl-Heinz Joeckel; Andreas J. Forstner; Markus M. Noethen; Marcella Rietschel; Alexander Sartorius; Laura Kranaster; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -)

doi:10.1002/ajmg.b.32700

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

Jerome C. Foo^*, Fabian Streit, Josef Frank, Jens Treutlein, Bernhard T. Baune, Susanne Moebus, Karl-Heinz Joeckel, Andreas J. Forstner, Markus M. Noethen, Marcella Rietschel, Alexander Sartorius, Laura Kranaster, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -)

^*Corresponding author for this work

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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.

Original language	English
Journal	American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume	180
Issue	1
Pages (from-to)	35-45
Number of pages	11
ISSN	1552-4841
DOIs	https://doi.org/10.1002/ajmg.b.32700
Publication status	Published - Jan 2019

Keywords

depression
electroconvulsive therapy
major depression
polygenic risk scores
treatment-resistance
DISORDER
ECT

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Foo, J. C., Streit, F., Frank, J., Treutlein, J., Baune, B. T., Moebus, S., Joeckel, K.-H., Forstner, A. J., Noethen, M. M., Rietschel, M., Sartorius, A., Kranaster, L., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -) (2019). Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 180(1), 35-45. https://doi.org/10.1002/ajmg.b.32700

@article{26c0f4b315f345febfbef81df5389f69,

title = "Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy",

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.",

keywords = "depression, electroconvulsive therapy, major depression, polygenic risk scores, treatment-resistance, DISORDER, ECT",

author = "Foo, \{Jerome C.\} and Fabian Streit and Josef Frank and Witt, \{Stephanie H.\} and Jens Treutlein and Baune, \{Bernhard T.\} and Susanne Moebus and Karl-Heinz Joeckel and Forstner, \{Andreas J.\} and Noethen, \{Markus M.\} and Marcella Rietschel and Alexander Sartorius and Laura Kranaster and Wray, \{Naomi R.\} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, \{Enda M.\} and Abdel Abdellaoui and Adams, \{Mark J.\} and Esben Agerbo and Air, \{Tracy M.\} and Andlauer, \{Till F. M.\} and Silviu-Alin Bacanu and Marie Baekvad-Hansen and Beekman, \{Aartjan T. F.\} and Bigdeli, \{Tim B.\} and Binder, \{Elisabeth B.\} and Blackwood, \{Douglas H. R.\} and Julien Bryois and Buttenschon, \{Henriette N.\} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, \{Jane Hvarregaard\} and Toni-Kim Clarke and Coleman, \{Jonathan R. I.\} and Lucia Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, \{Gregory E.\} and Jakob Grove and Hansen, \{Christine Soholm\} and Hansen, \{Thomas F.\} and Pedersen, \{Carsten Bocker\} and Pedersen, \{Marianne Giortz\} and Per Qvist and Jian Yang and Ole Mors and Mortensen, \{Preben Bo\} and \{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -)\}",

year = "2019",

month = jan,

doi = "10.1002/ajmg.b.32700",

language = "English",

volume = "180",

pages = "35--45",

journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley-Liss Inc.",

number = "1",

}

Foo, JC, Streit, F, Frank, J, Treutlein, J, Baune, BT, Moebus, S, Joeckel, K-H, Forstner, AJ, Noethen, MM, Rietschel, M, Sartorius, A, Kranaster, L & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -) 2019, 'Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, vol. 180, no. 1, pp. 35-45. https://doi.org/10.1002/ajmg.b.32700

Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy. / Foo, Jerome C.; Streit, Fabian; Frank, Josef et al.
In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 180, No. 1, 01.2019, p. 35-45.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

AU - Foo, Jerome C.

AU - Streit, Fabian

AU - Frank, Josef

AU - Witt, Stephanie H.

AU - Treutlein, Jens

AU - Baune, Bernhard T.

AU - Moebus, Susanne

AU - Joeckel, Karl-Heinz

AU - Forstner, Andreas J.

AU - Noethen, Markus M.

AU - Rietschel, Marcella

AU - Sartorius, Alexander

AU - Kranaster, Laura

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F. M.

AU - Bacanu, Silviu-Alin

AU - Baekvad-Hansen, Marie

AU - Beekman, Aartjan T. F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H. R.

AU - Bryois, Julien

AU - Buttenschon, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni-Kim

AU - Coleman, Jonathan R. I.

AU - Colodro-Conde, Lucia

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Grove, Jakob

AU - Hansen, Christine Soholm

AU - Hansen, Thomas F.

AU - Pedersen, Carsten Bocker

AU - Pedersen, Marianne Giortz

AU - Qvist, Per

AU - Yang, Jian

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (Jakob Grove, member of -)

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - depression

KW - electroconvulsive therapy

KW - major depression

KW - polygenic risk scores

KW - treatment-resistance

KW - DISORDER

KW - ECT

UR - https://www.scopus.com/pages/publications/85057967206

U2 - 10.1002/ajmg.b.32700

DO - 10.1002/ajmg.b.32700

M3 - Journal article

C2 - 30507021

SN - 1552-4841

VL - 180

SP - 35

EP - 45

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

IS - 1

ER -

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

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