Leif Oltedal1, Katherine L Narr2, Christopher Abbott3, Amit Anand4, Miklos Argyelan5, Hauke Bartsch6, Udo Dannlowski7, Annemieke Dols8, Philip van Eijndhoven9, Louise Emsell10, Vera Jane Erchinger11, Randall Espinoza2, Tim Hahn7, Lars G Hanson12, Gerhard Hellemann2, Martin Balslev Jorgensen13, Ute Kessler14, Mardien L Oudega8, Olaf B Paulson15, Ronny Redlich7, Pascal Sienaert10, Max L Stek8, Indira Tendolkar9, Mathieu Vandenbulcke10, Ketil J Oedegaard16, Anders M Dale17. 1. Department of Clinical Medicine, University of Bergen, Bergen, Norway; Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway; Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California. Electronic address: leif.oltedal@uib.no. 2. Departments of Neurology, Psychiatry, and Biobehavioral Sciences, University of California, Los Angeles, California. 3. Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque, New Mexico. 4. Cleveland Clinic, Center for Behavioral Health, Cleveland, Ohio. 5. Center for Psychiatric Neuroscience at the Feinstein Institute for Medical Research, New York, New York. 6. Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California. 7. Department of Psychiatry, University of Münster, Münster, Germany. 8. Department of Old Age Psychiatry, Vrije Universiteit Amsterdam/GGZ inGeest and the Neuroscience Campus, Amsterdam, the Netherlands. 9. Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry, Nijmegen, the Netherlands. 10. Katholieke Universiteit Leuven, University Psychiatric Center Katholieke Universiteit Leuven, Leuven, Belgium. 11. Department of Clinical Medicine, University of Bergen, Bergen, Norway. 12. Center for Magnetic Resonance, Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby, Denmark; Danish Research Centre for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark. 13. Psychiatric Center Copenhagen, Copenhagen, Denmark. 14. Department of Clinical Medicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway. 15. Danish Research Centre for Magnetic Resonance, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark; Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 16. Department of Clinical Medicine, University of Bergen, Bergen, Norway; Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Bergen, Norway. 17. Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, California; Department of Radiology, University of California, San Diego, La Jolla, California; Department of Neurosciences, University of California, San Diego, La Jolla, California.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069). CONCLUSIONS: 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.
Authors: Takahiro Soda; Declan M McLoughlin; Scott R Clark; Leif Oltedal; Ute Kessler; Jan Haavik; Chad Bousman; Daniel J Smith; Miquel Bioque; Caitlin C Clements; Colleen Loo; Fidel Vila-Rodriguez; Alessandra Minelli; Brian J Mickey; Roumen Milev; Anna R Docherty; Julie Langan Martin; Eric D Achtyes; Volker Arolt; Ronny Redlich; Udo Dannlowski; Narcis Cardoner; Emily Clare; Nick Craddock; Arianna Di Florio; Monika Dmitrzak-Weglarz; Liz Forty; Katherine Gordon-Smith; Mustafa Husain; Wendy M Ingram; Lisa Jones; Ian Jones; Mario Juruena; George Kirov; Mikael Landén; Daniel J Müller; Axel Nordensköld; Erik Pålsson; Meethu Paul; Agnieszka Permoda; Bartlomiej Pliszka; Jamie Rea; Klaus O Schubert; Joshua A Sonnen; Virginia Soria; Will Stageman; Akihiro Takamiya; Mikel Urretavizacaya; Stuart Watson; Maxim Zavorotny; Allan H Young; Eduard Vieta; Janusz K Rybakowski; Massimo Gennarelli; Peter P Zandi; Patrick F Sullivan; Bernhard T Baune Journal: Eur Arch Psychiatry Clin Neurosci Date: 2019-12-04 Impact factor: 5.270
Authors: Zhi-De Deng; Bruce Luber; Nicholas L Balderston; Melbaliz Velez Afanador; Michelle M Noh; Jeena Thomas; William C Altekruse; Shannon L Exley; Shriya Awasthi; Sarah H Lisanby Journal: Annu Rev Pharmacol Toxicol Date: 2020-01-06 Impact factor: 13.820
Authors: Mike M Schmitgen; Katharina M Kubera; Malte S Depping; Henrike M Nolte; Dusan Hirjak; Stefan Hofer; Julia H Hasenkamp; Ulrich Seidl; Bram Stieltjes; Klaus H Maier-Hein; Fabio Sambataro; Alexander Sartorius; Philipp A Thomann; Robert C Wolf Journal: Eur Arch Psychiatry Clin Neurosci Date: 2019-07-05 Impact factor: 5.270
Authors: Marta Cano; Erik Lee; Narcís Cardoner; Ignacio Martínez-Zalacaín; Jesús Pujol; Nikos Makris; Michael Henry; Esther Via; Rosa Hernández-Ribas; Oren Contreras-Rodríguez; José M Menchón; Mikel Urretavizcaya; Carles Soriano-Mas; Joan A Camprodon Journal: J Neuropsychiatry Clin Neurosci Date: 2018-11-21 Impact factor: 2.198
Authors: Olga Therese Ousdal; Giulio E Brancati; Ute Kessler; Vera Erchinger; Anders M Dale; Christopher Abbott; Leif Oltedal Journal: Biol Psychiatry Date: 2021-05-31 Impact factor: 13.382