Brain changes induced by electroconvulsive therapy (ECT) – understanding treatment mechanisms and predictors of clinical response.

 

Electroconvulsive therapy (ECT) is a procedure, done under general anesthesia, in which electric currents are passed through the brain, intentionally causing a brief seizure. Although ECT has remained the most effective acute treatment for major depressive episodes for nearly 80 years, how it works and why it is effective is not well known. Only a small proportion of patients with treatment resistant depression are offered ECT, and typically 60-80% experience a good response (> 50% symptom reduction).

Several neuroimaging studies of ECT have demonstrated volume increases of brain areas after treatment. The most consistent finding has been volume increase of the hippocampus. However, a link between the treatment induced brain changes and clinical improvement has not been established.

This project will explore how ECT changes the brain, and if the structural (or functional) changes that are seen can explain the effect (or side-effects) of the treatment.

An important reason for our knowledge gap is that single studies have limited samples and lack statistical power to reach firm conclusions. The Global ECT-MRI Research Collaboration was founded with a belief that collaboration and mega-analysis of combined data will lead to new knowledge that can be generalized across individual research sites.

Within GEMRIC we have the world’s largest data sample with clinical and MRI neuroimaging data before and after ECT – our initial study will include up to 550 subjects (including controls). In our next study we aim at increasing the sample size to 2000 subjects. GEMRIC uses state-of-the-art imaging tools, developed in a world leading laboratory (dr. Anders M Dale, UCSD) as well as tools developed by GEMRIC collaborators. Instead of distributing data among collaborators our philosophy is to collect all the data at a common data portal and then share analysis pipelines into this server. This way, data security can be kept at a very high level while at the same time almost any analysis pipeline can be used. Pipelines are set up as Docker containers – which means standardization, independence of operating systems and reproducible results.

New collaborators are welcome!

Project PI Leif Oltedal

Co-PI Ute Kessler; clinical effects of ECT

Co-PI Jan Haavik;  studies of Blood Biomarkers

Related Publications

2018

  • L. Oltedal, K. L. Narr, C. Abbott, A. Anand, M. Argyelan, H. Bartsch, U. Dannlowski, A. Dols, P. van Eijndhoven, L. Emsell, V. J. Erchinger, R. Espinoza, T. Hahn, L. G. Hanson, G. Hellemann, M. B. Jorgensen, U. Kessler, M. L. Oudega, O. B. Paulson, R. Redlich, P. Sienaert, M. L. Stek, I. Tendolkar, M. Vandenbulcke, K. J. Oedegaard, and A. M. Dale, “Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy,” Biological Psychiatry, vol. 84, iss. 8, pp. 574-581, 2018. doi:10.1016/j.biopsych.2018.05.017
    [BibTeX] [Abstract] [Download PDF]

    Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice. The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

    @article{Oltedal_BioPsych_2018,
    title = "Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy",
    journal = "Biological Psychiatry",
    volume = "84",
    number = "8",
    pages = "574 - 581",
    year = "2018",
    note = "Cannabinoids, Ketamine, Connectivity, and Depression",
    issn = "0006-3223",
    doi = "10.1016/j.biopsych.2018.05.017",
    url = "http://www.sciencedirect.com/science/article/pii/S0006322318315348",
    author = "Leif Oltedal and Katherine L. Narr and Christopher Abbott and Amit Anand and Miklos Argyelan and Hauke Bartsch and Udo Dannlowski and Annemieke Dols and Philip van Eijndhoven and Louise Emsell and Vera Jane Erchinger and Randall Espinoza and Tim Hahn and Lars G. Hanson and Gerhard Hellemann and Martin Balslev Jorgensen and Ute Kessler and Mardien L. Oudega and Olaf B. Paulson and Ronny Redlich and Pascal Sienaert and Max L. Stek and Indira Tendolkar and Mathieu Vandenbulcke and Ketil J. Oedegaard and Anders M. Dale",
    abstract = {
    
    Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome.
    
    Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice.
    
    The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.}
    }

2017

  • L. Oltedal, H. Bartsch, O. J. E. Sørhaug, U. Kessler, C. Abbott, A. Dols, M. L. Stek, L. Ersland, L. Emsell, P. van Eijndhoven, and others, “The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy,” NeuroImage: Clinical, vol. 14, pp. 422-432, 2017. doi:10.1016/j.nicl.2017.02.009
    [BibTeX] [Download PDF]
    @article{oltedal2017global,
      title={The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy},
      author={Oltedal, Leif and Bartsch, Hauke and S{\o}rhaug, Ole Johan Evjenth and Kessler, Ute and Abbott, Christopher and Dols, Annemieke and Stek, Max L and Ersland, Lars and Emsell, Louise and van Eijndhoven, Philip and others},
      journal={NeuroImage: Clinical},
      volume={14},
      pages={422--432},
      year={2017},
      publisher={Elsevier},
      url = {https://www.sciencedirect.com/science/article/pii/S2213158217300438},
      doi = "10.1016/j.nicl.2017.02.009"  
    }