Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy

Leif Oltedal; Katherine L Narr; Christopher Abbott; Amit Anand; Miklos Argyelan; Hauke Bartsch; Udo Dannlowski; Annemieke Dols; Philip van Eijndhoven; Louise Emsell; Vera Jane Erchinger; Randall Espinoza; Tim Hahn; Lars G Hanson; Gerhard Hellemann; Martin Balslev Jorgensen; Ute Kessler; Mardien L Oudega; Olaf B Paulson; Ronny Redlich; Pascal Sienaert; Max L Stek; Indira Tendolkar; Mathieu Vandenbulcke; Ketil J Oedegaard; Anders M Dale

doi:10.1016/j.biopsych.2018.05.017

Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy

Biol Psychiatry. 2018 Oct 15;84(8):574-581. doi: 10.1016/j.biopsych.2018.05.017. Epub 2018 May 29.

Authors

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

Affiliations

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.

Keywords: Antidepressant response; Biomarker; Brain; Depression; ECT; Neuroimaging.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Biomarkers
Case-Control Studies
Depressive Disorder, Major / pathology*
Depressive Disorder, Major / therapy*
Electroconvulsive Therapy*
Female
Functional Laterality
Hippocampus / diagnostic imaging
Hippocampus / pathology*
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neuroimaging
Organ Size
Psychiatric Status Rating Scales
Treatment Outcome

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding