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Published Online: 7 September 2022

Association Between Polygenic Risk Scores and Outcome of ECT

Robert Sigström, M.D., Ph.D. [email protected], Kaarina Kowalec, Ph.D., Lina Jonsson, Ph.D., Caitlin C. Clements, Ph.D., Robert Karlsson, Ph.D., Axel Nordenskjöld, M.D., Ph.D., Erik Pålsson, Ph.D., Patrick F. Sullivan, M.D., and Mikael Landén, M.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 179, Number 11
https://doi.org/10.1176/appi.ajp.22010045
CME
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Abstract

Objective:

Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.

Methods:

Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.

Results:

Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.

Conclusions:

Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.

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Supplementary Material

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 179 • Number 11 • November 01, 2022
Pages: 844 - 852
PubMed: 36069021

History

Received: 15 January 2022
Revision received: 2 May 2022
Accepted: 17 May 2022
Published online: 7 September 2022
Published in print: November 01, 2022

Keywords

  1. Electroconvulsive Therapy (ECT)
  2. Depressive Disorders
  3. Bipolar and Related Disorders
  4. Genetics/Genomics

Authors

Affiliations

Robert Sigström, M.D., Ph.D. [email protected]
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Kaarina Kowalec, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Lina Jonsson, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Caitlin C. Clements, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Robert Karlsson, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Axel Nordenskjöld, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Erik Pålsson, Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Patrick F. Sullivan, M.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Mikael Landén, M.D., Ph.D.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (Sigström, Jonsson, Pålsson, Landén); Department of Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden (Sigström); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Kowalec, Clements, Karlsson, Sullivan, Landén); College of Pharmacy, University of Manitoba, Winnipeg, Canada (Kowalec); Department of Psychology, University of Pennsylvania, Philadelphia (Clements); University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden (Nordenskjöld); Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill (Sullivan).
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Notes

Send correspondence to Dr. Sigström ([email protected]).

Competing Interests

Drs. Nordenskjöld and Landén have received lecture honoraria from Lundbeck Pharmaceutical. Dr. Landén has served as a consultant for AstraZeneca. Dr. Sullivan has served as a consultant for and is a shareholder in Neumora Therapeutics. The other authors report no financial relationships with commercial interests.

Funding Information

Supported by grants from the Swedish Research Council (2018-02653 and 2018-05973 to Dr. Landén), the Swedish Foundation for Strategic Research (KF10-0039 to Dr. Landén), and the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (ALFGBG-716801 to Dr. Landén). Dr. Sigström was supported by a grant from the Swedish state under the ALF agreement (ALFGBG-942684). Dr. Kowalec was supported by a grant from the University of Manitoba and by a grant from NIMH (R01MH123724). Dr. Sullivan was supported by a grant from the Swedish Research Council (Vetenskapsrådet, award D0886501). Dr. Landén was supported by a grant from the Wenner-Gren Foundation (SSv2019-0008).

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