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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 (R2) 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, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 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 languageEnglish
Pages (from-to)531-539
Number of pages9
JournalBiological Psychiatry
Issue number6
Early online date24 Oct 2021
Publication statusPublished - 15 Mar 2022




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