Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Jurjen J Luykx; Dore Loef; Bochao Lin; Linda van Diermen; Jasper O Nuninga; Eric van Exel; Mardien L Oudega; Didi Rhebergen; Sigfried N T M Schouws; Philip van Eijndhoven; Esmée Verwijk; Didier Schrijvers; Tom K Birkenhager; Karen M Ryan; Baer Arts; Suzanne C van Bronswijk; Gunter Kenis; Geert Schurgers; Bernhard T Baune; Martijn Arns; Edwin E van Dellen; Metten Somers; Iris E C Sommer; Marco P Boks; Sinan Gülöksüz; Declan M McLoughlin; Annemiek Dols; Bart P F Rutten

doi:10.1016/j.biopsych.2021.10.013

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Jurjen J Luykx, Dore Loef, Bochao Lin, Linda van Diermen, Jasper O Nuninga, Eric van Exel, Mardien L Oudega, Didi Rhebergen, Sigfried N T M Schouws, Philip van Eijndhoven, Esmée Verwijk, Didier Schrijvers, Tom K Birkenhager, Karen M Ryan, Baer Arts, Suzanne C van Bronswijk, Gunter Kenis, Geert Schurgers, Bernhard T Baune, Martijn ArnsEdwin E van Dellen, Metten Somers, Iris E C Sommer, Marco P Boks, Sinan Gülöksüz, Declan M McLoughlin, Annemiek Dols, Bart P F Rutten

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Abstract

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R ²) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R ² = 6.94%, p < .0001), which was consistent across countries: Ireland (R ² = 8.18%, p = .0013), Belgium (R ² = 6.83%, p = .016), and the Netherlands (R ² = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R ² = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R ² = 4.42%, p = .0024) and unipolar MDE only (R ² = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

Original language	English
Pages (from-to)	531-539
Number of pages	9
Journal	Biological Psychiatry
Volume	91
Issue number	6
Early online date	24 Oct 2021
DOIs	https://doi.org/10.1016/j.biopsych.2021.10.013
Publication status	Published - 15 Mar 2022

Keywords

Depression
Electroconvulsive therapy (ECT)
Polygenic liabilities
Schizophrenia

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Luykx, J. J., Loef, D., Lin, B., van Diermen, L., Nuninga, J. O., van Exel, E., Oudega, M. L., Rhebergen, D., Schouws, S. N. T. M., van Eijndhoven, P., Verwijk, E., Schrijvers, D., Birkenhager, T. K., Ryan, K. M., Arts, B., van Bronswijk, S. C., Kenis, G., Schurgers, G., Baune, B. T., ... Rutten, B. P. F. (2022). Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness. Biological Psychiatry, 91(6), 531-539. https://doi.org/10.1016/j.biopsych.2021.10.013

@article{e4fedcc506f244b4b109ad8752e0a05f,

title = "Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness",

abstract = "Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry. ",

keywords = "Depression, Electroconvulsive therapy (ECT), Polygenic liabilities, Schizophrenia",

author = "Luykx, {Jurjen J} and Dore Loef and Bochao Lin and {van Diermen}, Linda and Nuninga, {Jasper O} and {van Exel}, Eric and Oudega, {Mardien L} and Didi Rhebergen and Schouws, {Sigfried N T M} and {van Eijndhoven}, Philip and Esm{\'e}e Verwijk and Didier Schrijvers and Birkenhager, {Tom K} and Ryan, {Karen M} and Baer Arts and {van Bronswijk}, {Suzanne C} and Gunter Kenis and Geert Schurgers and Baune, {Bernhard T} and Martijn Arns and {van Dellen}, {Edwin E} and Metten Somers and Sommer, {Iris E C} and Boks, {Marco P} and Sinan G{\"u}l{\"o}ks{\"u}z and McLoughlin, {Declan M} and Annemiek Dols and Rutten, {Bart P F}",

note = "Funding Information: This study was funded by an Asp{\'a}sia Grant from the Dutch Research Council ; Health Research Board , Ireland (Grant Nos. TRA/2007/5 and HPF/2010/17 to [DMM]); and a personal Rudolf Magnus Talent Fellowship from University Medical Center Utrecht (Grant No. H150 to [to JJL]). BPFR was funded by a VIDI award number 91718336 from the Netherlands Scientific Organization. Funding Information: This study was funded by an Asp{\'a}sia Grant from the Dutch Research Council; Health Research Board, Ireland (Grant Nos. TRA/2007/5 and HPF/2010/17 to [DMM]); and a personal Rudolf Magnus Talent Fellowship from University Medical Center Utrecht (Grant No. H150 to [to JJL]). BPFR was funded by a VIDI award number 91718336 from the Netherlands Scientific Organization. JJL, AD, and BPFR were responsible for study conception. BL and DL were responsible for data analysis. DMM, LvD, AD, EvE, MLO, DR, SNTMS, MPB, JON, IECS, BA, and BPFR contributed samples. JJL, GK, BPFR, and MPB contributed genotyping. DL, AD, JJL, BL, and BPFR were responsible for the first draft of the manuscript. JJL, DL, BL, LvD, JON, EvE, MLO, DR, SNTMS, PvE, EV, DS, TKB, KMR, BA, GS, GK, SCvB, BTB, MA, EEvD, IECS, MS, MPB, SG, DMM, AD, and BPFR were responsible for critical revision of the final draft. BTB reports having received speaker and consultation fees from AstraZeneca, Lundbeck, Pfizer, Takeda, Servier, Bristol-Myers Squibb, Otsuka, LivaNova, and Janssen-Cilag. DMM has received speaker's honoraria from MECTA and Otsuka and an honorarium from Janssen for participating in an esketamine advisory board meeting. All of these were unrelated to the current work. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2021 Society of Biological Psychiatry",

year = "2022",

month = mar,

day = "15",

doi = "10.1016/j.biopsych.2021.10.013",

language = "English",

volume = "91",

pages = "531--539",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier USA",

number = "6",

}

Luykx, JJ, Loef, D, Lin, B, van Diermen, L, Nuninga, JO, van Exel, E, Oudega, ML, Rhebergen, D, Schouws, SNTM, van Eijndhoven, P, Verwijk, E, Schrijvers, D, Birkenhager, TK, Ryan, KM, Arts, B, van Bronswijk, SC, Kenis, G, Schurgers, G, Baune, BT, Arns, M, van Dellen, EE, Somers, M, Sommer, IEC, Boks, MP, Gülöksüz, S, McLoughlin, DM, Dols, A & Rutten, BPF 2022, 'Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness', Biological Psychiatry, vol. 91, no. 6, pp. 531-539. https://doi.org/10.1016/j.biopsych.2021.10.013

TY - JOUR

T1 - Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

AU - Luykx, Jurjen J

AU - Loef, Dore

AU - Lin, Bochao

AU - van Diermen, Linda

AU - Nuninga, Jasper O

AU - van Exel, Eric

AU - Oudega, Mardien L

AU - Rhebergen, Didi

AU - Schouws, Sigfried N T M

AU - van Eijndhoven, Philip

AU - Verwijk, Esmée

AU - Schrijvers, Didier

AU - Birkenhager, Tom K

AU - Ryan, Karen M

AU - Arts, Baer

AU - van Bronswijk, Suzanne C

AU - Kenis, Gunter

AU - Schurgers, Geert

AU - Baune, Bernhard T

AU - Arns, Martijn

AU - van Dellen, Edwin E

AU - Somers, Metten

AU - Sommer, Iris E C

AU - Boks, Marco P

AU - Gülöksüz, Sinan

AU - McLoughlin, Declan M

AU - Dols, Annemiek

AU - Rutten, Bart P F

N1 - Funding Information: This study was funded by an Aspásia Grant from the Dutch Research Council ; Health Research Board , Ireland (Grant Nos. TRA/2007/5 and HPF/2010/17 to [DMM]); and a personal Rudolf Magnus Talent Fellowship from University Medical Center Utrecht (Grant No. H150 to [to JJL]). BPFR was funded by a VIDI award number 91718336 from the Netherlands Scientific Organization. Funding Information: This study was funded by an Aspásia Grant from the Dutch Research Council; Health Research Board, Ireland (Grant Nos. TRA/2007/5 and HPF/2010/17 to [DMM]); and a personal Rudolf Magnus Talent Fellowship from University Medical Center Utrecht (Grant No. H150 to [to JJL]). BPFR was funded by a VIDI award number 91718336 from the Netherlands Scientific Organization. JJL, AD, and BPFR were responsible for study conception. BL and DL were responsible for data analysis. DMM, LvD, AD, EvE, MLO, DR, SNTMS, MPB, JON, IECS, BA, and BPFR contributed samples. JJL, GK, BPFR, and MPB contributed genotyping. DL, AD, JJL, BL, and BPFR were responsible for the first draft of the manuscript. JJL, DL, BL, LvD, JON, EvE, MLO, DR, SNTMS, PvE, EV, DS, TKB, KMR, BA, GS, GK, SCvB, BTB, MA, EEvD, IECS, MS, MPB, SG, DMM, AD, and BPFR were responsible for critical revision of the final draft. BTB reports having received speaker and consultation fees from AstraZeneca, Lundbeck, Pfizer, Takeda, Servier, Bristol-Myers Squibb, Otsuka, LivaNova, and Janssen-Cilag. DMM has received speaker's honoraria from MECTA and Otsuka and an honorarium from Janssen for participating in an esketamine advisory board meeting. All of these were unrelated to the current work. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological Psychiatry

PY - 2022/3/15

Y1 - 2022/3/15

N2 - Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

AB - Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

KW - Depression

KW - Electroconvulsive therapy (ECT)

KW - Polygenic liabilities

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85121732875&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2021.10.013

DO - 10.1016/j.biopsych.2021.10.013

M3 - Article

C2 - 34955169

SN - 0006-3223

VL - 91

SP - 531

EP - 539

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 6

ER -

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

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