Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness.
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Authors
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
Issue Date
2021-10-24
Type
Journal Article
Research Support, Non-U.S. Gov't
Research Support, Non-U.S. Gov't
Language
en
Keywords
Depression , Electroconvulsive therapy (ECT) , Polygenic liabilities , Schizophrenia
Alternative Title
Abstract
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.
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) at the optimal p-value threshold is reported.
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 = 6.94%, p < .0001), which was consistent across countries: Ireland (R = 8.18%, p = .0013), Belgium (R = 6.83%, p = .016), and the Netherlands (R = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R = 4.42%, p = .0024) and unipolar MDE only (R = 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.
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.
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) at the optimal p-value threshold is reported.
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 = 6.94%, p < .0001), which was consistent across countries: Ireland (R = 8.18%, p = .0013), Belgium (R = 6.83%, p = .016), and the Netherlands (R = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R = 4.42%, p = .0024) and unipolar MDE only (R = 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.
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.
Description
Citation
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., Arns, M., … 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
Publisher
License
Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Journal
Biological psychiatry
Volume
91
Issue
6
PubMed ID
ISSN
1873-2402