Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness
Luykx, Jurjen J; Loef, Dore; Lin, Bochao; van Diermen, Linda; Nuninga, Jasper O; van Exel, Eric; Oudega, Mardien L; Rhebergen, Didi; Schouws, Sigfried N T M; van Eijndhoven, Philip; Verwijk, Esmée; Schrijvers, Didier; Birkenhager, Tom K; Ryan, Karen M; Arts, Baer; van Bronswijk, Suzanne C; Kenis, Gunter; Schurgers, Geert; Baune, Bernhard T; Arns, Martijn; van Dellen, Edwin E; Somers, Metten; Sommer, Iris E C; Boks, Marco P; Gülöksüz, Sinan; McLoughlin, Declan M; Dols, Annemiek; Rutten, Bart P F
(2022) Biological Psychiatry, volume 91, issue 6, pp. 531 - 539
(Article)
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
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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.
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Keywords: Depression, Electroconvulsive therapy (ECT), Polygenic liabilities, Schizophrenia, Biological Psychiatry, Journal Article
ISSN: 0006-3223
Publisher: Elsevier USA
Note: 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
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