Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

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

doi:10.1016/j.biopsych.2021.10.013

Abstract

BackgroundElectroconvulsive 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. MethodsA 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. ResultsIn 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. ConclusionsA 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.

Highlights

Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDE)
We examined whether Polygenic risk scores (PRSs) for major depressive disorder, schizophrenia, cross-disorder, and pharmacological antidepressant response are associated with ECT
In the 266 subjects passing quality control, PRS-schizophrenia was positively associated with larger HDRS decrease in linear regression, which was consistent across countries: Ireland (R2=8.18%, p=0.0013), Belgium (R2=6.83%, p=0.016), and the Netherlands (R2=7.92%, p=0.0077)

Summary

Introduction

Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDE). 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. We examined whether PRSs for major depressive disorder, schizophrenia, cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness

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Results

Conclusion