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.

Project PI Leif Oltedal

Co-PI Ute Kessler; clinical effects of ECT

Co-PI Jan Haavik;  studies of Blood Biomarkers

Related Publications

2021

  • A. Takamiya, A. Dols, L. Emsell, C. Abbott, A. Yrondi, C. Soriano Mas, M. B. Jorgensen, …, L. Oltedal, and T. Kishimoto, “Neural Substrates of Psychotic Depression: Findings From the Global ECT-MRI Research Collaboration,” Schizophrenia Bulletin, 2021. doi:10.1093/schbul/sbab122
    [BibTeX] [Download PDF]
    @article{takamiya2021neural,
      title        = {Neural Substrates of Psychotic Depression: Findings From the Global ECT-MRI Research Collaboration},
      author       = {Takamiya, Akihiro and Dols, Annemiek and Emsell, Louise and Abbott, Christopher and Yrondi, Antoine and Soriano Mas, Carles and Jorgensen, Martin Balslev and ... and Oltedal, Leif and Kishimoto, Taishiro},
      year         = 2021,
      journal      = {Schizophrenia Bulletin},
      doi          = {10.1093/schbul/sbab122},
      url          = {https://pubmed.ncbi.nlm.nih.gov/34624103/}
    }

  • G. E. Brancati, N. Brekke, H. Bartsch, O. J. E. Sørhaug, O. T. Ousdal, Å. Hammar, P. M. Schuster, K. J. Oedegaard, U. Kessler, and L. Oltedal, “Short and long-term effects of single and multiple sessions of electroconvulsive therapy on brain gray matter volumes,” Brain Stimulation, vol. 14, iss. 5, pp. 1330-1339, 2021. doi:https://doi.org/10.1016/j.brs.2021.08.018
    [BibTeX] [Abstract] [Download PDF]

    Background Electroconvulsive therapy (ECT) has been shown to induce broadly distributed cortical and subcortical volume increases, more prominently in the amygdala and the hippocampus. Structural changes after one ECT session and in the long-term have been understudied. Objective The aim of this study was to describe short-term and long-term volume changes induced in cortical and subcortical regions by ECT. Methods Structural brain data were acquired from depressed patients before and 2 h after their first ECT session, 7–14 days after the end of the ECT series and at 6 months follow up (N = 34). Healthy, age and gender matched volunteers were scanned according to the same schedule (N = 18) and patients affected by atrial fibrillation were scanned 1–2 h before and after undergoing electrical cardioversion (N = 16). Images were parcelled using FreeSurfer and estimates of cortical gray matter volume and subcortical volume changes were obtained using Quarc. Results Volume increase was observable in most of gray matter regions after 2 h from the first ECT session, with significant results in brain stem, bilateral hippocampi, right putamen and left thalamus, temporal and occipital regions in the right hemisphere. At the end of treatment series, widespread significant volume changes were observed. After six months, the right amygdala volume was still significantly increased. No significant changes were observed in the comparison groups. Conclusions Volume increases in gray matter areas can be detected 2 h after a single ECT session. Further studies are warranted to explore the underlying molecular mechanisms.

    @article{Brancati2021,
      title        = {Short and long-term effects of single and multiple sessions of electroconvulsive therapy on brain gray matter volumes},
      author       = {Giulio Emilio Brancati and Njål Brekke and Hauke Bartsch and Ole Johan {Evjenth Sørhaug} and Olga Therese Ousdal and Åsa Hammar and Peter Moritz Schuster and Ketil Joachim Oedegaard and Ute Kessler and Leif Oltedal},
      year         = 2021,
      journal      = {Brain Stimulation},
      volume       = 14,
      number       = 5,
      pages        = {1330--1339},
      doi          = {https://doi.org/10.1016/j.brs.2021.08.018},
      issn         = {1935-861X},
      url          = {https://www.sciencedirect.com/science/article/pii/S1935861X21002205},
      abstract     = {Background Electroconvulsive therapy (ECT) has been shown to induce broadly distributed cortical and subcortical volume increases, more prominently in the amygdala and the hippocampus. Structural changes after one ECT session and in the long-term have been understudied. Objective The aim of this study was to describe short-term and long-term volume changes induced in cortical and subcortical regions by ECT. Methods Structural brain data were acquired from depressed patients before and 2 h after their first ECT session, 7–14 days after the end of the ECT series and at 6 months follow up (N = 34). Healthy, age and gender matched volunteers were scanned according to the same schedule (N = 18) and patients affected by atrial fibrillation were scanned 1–2 h before and after undergoing electrical cardioversion (N = 16). Images were parcelled using FreeSurfer and estimates of cortical gray matter volume and subcortical volume changes were obtained using Quarc. Results Volume increase was observable in most of gray matter regions after 2 h from the first ECT session, with significant results in brain stem, bilateral hippocampi, right putamen and left thalamus, temporal and occipital regions in the right hemisphere. At the end of treatment series, widespread significant volume changes were observed. After six months, the right amygdala volume was still significantly increased. No significant changes were observed in the comparison groups. Conclusions Volume increases in gray matter areas can be detected 2 h after a single ECT session. Further studies are warranted to explore the underlying molecular mechanisms.}
    }

  • B. S. C. Wade, G. Hellemann, R. T. Espinoza, R. P. Woods, S. H. Joshi, R. Redlich, U. Dannlowski, A. Jorgensen, C. C. Abbott, L. Oltedal, and K. L. Narr, “Accounting for symptom heterogeneity can improve neuroimaging models of antidepressant response after electroconvulsive therapy,” Human Brain Mapping, 2021. doi:https://doi.org/10.1002/hbm.25620
    [BibTeX] [Download PDF]
    @article{Wade2021,
      title        = {Accounting for symptom heterogeneity can improve neuroimaging models of antidepressant response after electroconvulsive therapy},
      author       = {Wade, Benjamin S. C. and Hellemann, Gerhard and Espinoza, Randall T. and Woods, Roger P. and Joshi, Shantanu H. and Redlich, Ronny and Dannlowski, Udo and Jorgensen, Anders and Abbott, Christopher C. and Oltedal, Leif and Narr, Katherine L.},
      journal      = {Human Brain Mapping},
      doi          = {https://doi.org/10.1002/hbm.25620},
      url          = {https://onlinelibrary.wiley.com/doi/abs/10.1002/hbm.25620},
      keywords     = {electroconvulsive therapy, machine learning, major depressive disorder, structural neuroimaging, symptom heterogeneity},
      year       = 2021
    }

  • O. T. Ousdal, G. E. Brancati, U. Kessler, V. Erchinger, A. M. Dale, C. Abbott, and L. Oltedal, “The neurobiological effects of electroconvulsive therapy studied through magnetic resonance–what have we learnt and where do we go?,” Biological Psychiatry, 2021. doi:10.1016/j.biopsych.2021.05.023
    [BibTeX] [Download PDF]
    @article{ousdal2021neurobiological,
      title        = {The neurobiological effects of electroconvulsive therapy studied through magnetic resonance--what have we learnt and where do we go?},
      author       = {Ousdal, Olga Therese and Brancati, Giulio E and Kessler, Ute and Erchinger, Vera and Dale, Anders M and Abbott, Christopher and Oltedal, Leif},
      year         = 2021,
      journal      = {Biological Psychiatry},
      publisher    = {Elsevier},
      doi          = {10.1016/j.biopsych.2021.05.023},
      url          = {https://pubmed.ncbi.nlm.nih.gov/34274106/}
    }

  • N. Opel, K. Narr, C. Abbott, M. Argyelan, …, O. Ousdal, J. Haavik, Å. Hammar, K. Oedegaard, U. Kessler, H. Bartsch, A. Dale, B. Baune, U. Dannlowski, L. Oltedal, and R. Redlich, “Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy,” Journal of psychiatry & neuroscience, vol. 46, iss. 6, p. PE418–E426, 2021. doi:10.1503/jpn.200176
    [BibTeX] [Download PDF]
    @article{opel2021elevated,
      title        = {Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy},
      author       = {Opel, N and Narr, KL and Abbott, C and Argyelan, M and ... and Ousdal, OT and Haavik, J and Hammar, {\AA} and Oedegaard, KJ and Kessler, U and Bartsch, H and Dale, AM and Baune, BT and Dannlowski, U and Oltedal, L and Redlich, R},
      year         = 2021,
      journal      = {Journal of psychiatry \& neuroscience},
      volume       = 46,
      number       = 6,
      pages        = {PE418–E426},
      doi          = {10.1503/jpn.200176},
      url          = {https://pubmed.ncbi.nlm.nih.gov/34223741/}
    }

  • V. J. Erchinger, L. Ersland, S. M. Aukland, C. C. Abbott, and L. Oltedal, “Magnetic Resonance Spectroscopy in Depressed Subjects Treated With Electroconvulsive Therapy—A Systematic Review of Literature,” Frontiers in Psychiatry, vol. 12, p. 326, 2021. doi:10.3389/fpsyt.2021.608857
    [BibTeX] [Download PDF]
    @article{erchinger2021magnetic,
      title        = {Magnetic Resonance Spectroscopy in Depressed Subjects Treated With Electroconvulsive Therapy—A Systematic Review of Literature},
      author       = {Erchinger, Vera Jane and Ersland, Lars and Aukland, Stein Magnus and Abbott, Christopher C. and Oltedal, Leif},
      year         = 2021,
      journal      = {Frontiers in Psychiatry},
      volume       = 12,
      pages        = 326,
      doi          = {10.3389/fpsyt.2021.608857},
      issn         = {1664-0640},
      url          = {https://www.frontiersin.org/article/10.3389/fpsyt.2021.608857}
    }

2020

  • V. J. Erchinger, J. Miller, T. Jones, U. Kessler, J. Bustillo, J. Haavik, J. Petrillo, G. Ziomek, Å. Hammar, K. J. Oedegaard, V. D. Calhoun, S. M. McClintock, L. Ersland, L. Oltedal, and C. C. Abbott, “Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy,” Brain and Behavior, 2020. doi:10.1002/brb3.1833
    [BibTeX] [Download PDF]
    @article{erchinger2020ect,
      title        = {Anterior cingulate gamma-aminobutyric acid concentrations and electroconvulsive therapy},
      author       = {Erchinger, V. J. and Miller, J. and Jones, T. and Kessler, U.  and Bustillo,  J.  and Haavik,J. and Petrillo, J. and Ziomek, G. and Hammar, {\AA}. and Oedegaard,  K. J. and Calhoun,  V. D. and McClintock,  S. M. and Ersland,  L. and Oltedal, L.  and Abbott, C. C.},
      year         = 2020,
      journal      = {Brain and Behavior},
      publisher    = {Wiley},
      doi          = {10.1002/brb3.1833},
      url          = {https://onlinelibrary.wiley.com/doi/10.1002/brb3.1833}
    }

  • O. T. Ousdal, R. Gjestad, and L. Oltedal, “Reply to: Clinical Relevance of Brain Changes After Electroconvulsive Therapy: Is There Really No Link at All?,” Biological psychiatry, 2020. doi:10.1016/j.biopsych.2020.05.031
    [BibTeX] [Download PDF]
    @article{ousdal2020electroconvulsive,
      title        = {Reply to: Clinical Relevance of Brain Changes After Electroconvulsive Therapy: Is There Really No Link at All?},
      author       = {Ousdal, Olga Therese and Gjestad, Rolf and Oltedal, Leif},
      year         = 2020,
      journal      = {Biological psychiatry},
      doi          = {10.1016/j.biopsych.2020.05.031},
      url          = {https://pubmed.ncbi.nlm.nih.gov/32768147/}
    }

  • M. Blomberg, M. Semkovska, U. Kessler, V. J. Erchinger, K. J. Oedegaard, L. Oltedal, and Å. Hammar, “A Longitudinal Comparison Between Depressed Patients Receiving Electroconvulsive Therapy and Healthy Controls on Specific Memory Functions,” Prim Care Companion CNS Disord., vol. 22, iss. 3, 2020. doi:10.4088/PCC.19m02547
    [BibTeX] [Download PDF]
    @article{blomberg2020longitudinal,
      title        = {A Longitudinal Comparison Between Depressed Patients Receiving Electroconvulsive Therapy and Healthy Controls on Specific Memory Functions},
      author       = {Blomberg, Malin and Semkovska, Maria and Kessler, Ute and Erchinger, Vera Jane and Oedegaard, Ketil J and Oltedal, Leif and Hammar, {\AA}sa},
      year         = 2020,
      journal      = {Prim Care Companion CNS Disord.},
      volume       = 22,
      number       = 3,
      doi          = {10.4088/PCC.19m02547},
      url          = {https://www.ncbi.nlm.nih.gov/pubmed/32408397}
    }

  • P. C. Mulders, A. Llera, C. F. Beckmann, M. Vandenbulcke, M. Stek, P. Sienaert, R. Redlich, G. Petrides, M. L. Oudega, L. Oltedal, and others, “Structural changes induced by electroconvulsive therapy are associated with clinical outcome,” Brain Stimulation, 2020. doi:10.1016/j.brs.2020.02.020
    [BibTeX] [Download PDF]
    @article{mulders2020structural,
      title        = {Structural changes induced by electroconvulsive therapy are associated with clinical outcome},
      author       = {Mulders, Peter CR and Llera, Alberto and Beckmann, Christian F and Vandenbulcke, Mathieu and Stek, Max and Sienaert, Pascal and Redlich, Ronny and Petrides, Georgios and Oudega, Mardien Leoniek and Oltedal, Leif and others},
      year         = 2020,
      journal      = {Brain Stimulation},
      publisher    = {Elsevier},
      doi          = {10.1016/j.brs.2020.02.020},
      url          = {https://www.sciencedirect.com/science/article/pii/S1935861X20300425}
    }

2019

  • M. Argyelan, L. Oltedal, Z. Deng, B. Wade, M. Bikson, A. Joanlanne, S. Sanghani, H. Bartsch, M. Cano, A. M. Dale, and others, “Electric field causes volumetric changes in the human brain,” eLife, vol. 8, p. e49115, 2019. doi:10.7554/eLife.49115
    [BibTeX] [Download PDF]
    @article{argyelan2019electric,
      title        = {Electric field causes volumetric changes in the human brain},
      author       = {Argyelan, Miklos and Oltedal, Leif and Deng, Zhi-De and Wade, Benjamin and Bikson, Marom and Joanlanne, Andrea and Sanghani, Sohag and Bartsch, Hauke and Cano, Marta and Dale, Anders M and others},
      year         = 2019,
      journal      = {eLife},
      publisher    = {eLife Sciences Publications Limited},
      volume       = 8,
      pages        = {e49115},
      doi          = {10.7554/eLife.49115},
      url          = {"https://www.ncbi.nlm.nih.gov/pubmed/31644424}
    }

  • O. T. Ousdal, M. Argyelan, K. L. Narr, C. Abbott, B. Wade, M. Vandenbulcke, M. Urretavizcaya, I. Tendolkar, A. Takamiya, M. L. Stek, and others, “Brain changes induced by Electroconvulsive Therapy are broadly distributed,” Biological Psychiatry, 2019. doi:10.1016/j.biopsych.2019.07.010
    [BibTeX] [Download PDF]
    @article{ousdal2019brain,
      title        = {Brain changes induced by Electroconvulsive Therapy are broadly distributed},
      author       = {Ousdal, Olga Therese and Argyelan, Miklos and Narr, Katherine L and Abbott, Christopher and Wade, Benjamin and Vandenbulcke, Mathieu and Urretavizcaya, Mikel and Tendolkar, Indira and Takamiya, Akihiro and Stek, Max L and others},
      year         = 2019,
      journal      = {Biological Psychiatry},
      publisher    = {Elsevier},
      doi          = {10.1016/j.biopsych.2019.07.010},
      url          = {https://www.ncbi.nlm.nih.gov/pubmed/31561859}
    }

  • B. S. Wade, G. Hellemann, R. T. Espinoza, R. P. Woods, S. H. Joshi, R. Redlich, A. Jørgensen, C. C. Abbott, K. J. Ødegaard, S. M. McClintock, L. Oltedal, and K. Narr, “Depressive Symptom Dimensions in Treatment-Resistant Major Depression and Their Modulation With Electroconvulsive Therapy,” The journal of ECT, 2019. doi:10.1097/YCT.0000000000000623
    [BibTeX] [Download PDF]
    @article{wade2019depressive,
      title        = {Depressive Symptom Dimensions in Treatment-Resistant Major Depression and Their Modulation With Electroconvulsive Therapy},
      author       = {Wade, Benjamin SC and Hellemann, Gerhard and Espinoza, Randall T and Woods, Roger P and Joshi, Shantanu H and Redlich, Ronny and J{\o}rgensen, Anders and Abbott, Christopher C and {\O}degaard, Ketil Joachim and McClintock, Shawn M and Oltedal, L and Narr, KL},
      year         = 2019,
      journal      = {The journal of ECT},
      publisher    = {LWW},
      doi          = {10.1097/YCT.0000000000000623},
      url          = {https://www.ncbi.nlm.nih.gov/m/pubmed/31464814/}
    }

  • T. I. M. Aarsland, I. Leskauskaite, Ø. Midttun, A. Ulvik, P. M. Ueland, L. Oltedal, V. J. Erchinger, K. J. Ødegaard, J. Haavik, and U. Kessler, “The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites,” Brain Stimulation, 2019. doi:10.1016/j.brs.2019.05.018
    [BibTeX] [Download PDF]
    @article{aarsland2019effect,
      title        = {The effect of electroconvulsive therapy (ECT) on serum tryptophan metabolites},
      author       = {Aarsland, Tore Ivar Malmei and Leskauskaite, Ieva and Midttun, {\O}ivind and Ulvik, Arve and Ueland, Per Magne and Oltedal, Leif and Erchinger, Vera Jane and {\O}degaard, Ketil Joachim and Haavik, Jan and Kessler, Ute},
      year         = 2019,
      journal      = {Brain Stimulation},
      publisher    = {Elsevier},
      doi          = {10.1016/j.brs.2019.05.018},
      url          = {https://www.sciencedirect.com/science/article/pii/S1935861X19302256}
    }

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},
      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},
      year         = 2018,
      journal      = {Biological Psychiatry},
      volume       = 84,
      number       = 8,
      pages        = {574--581},
      doi          = {10.1016/j.biopsych.2018.05.017},
      issn         = {0006-3223},
      url          = {http://www.sciencedirect.com/science/article/pii/S0006322318315348},
      note         = {Cannabinoids, Ketamine, Connectivity, and Depression},
      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},
      year         = 2017,
      journal      = {NeuroImage: Clinical},
      publisher    = {Elsevier},
      volume       = 14,
      pages        = {422--432},
      doi          = {10.1016/j.nicl.2017.02.009},
      url          = {https://www.sciencedirect.com/science/article/pii/S2213158217300438}
    }