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Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis

  • Gregor Gryglewski (a1), Pia Baldinger-Melich (a2), René Seiger (a3), Godber Mathis Godbersen (a1), Paul Michenthaler (a1), Manfred Klöbl (a4), Benjamin Spurny (a4), Alexander Kautzky (a1), Thomas Vanicek (a1), Siegfried Kasper (a5), Richard Frey (a6) and Rupert Lanzenberger (a7)...
Abstract
Background

Electroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported.

Aims

To investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov – NCT02379767).

Method

MRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre–post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored.

Results

Increases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal–amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere.

Conclusions

Following ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood.

Declaration of interest

S.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Correspondence: Professor Rupert Lanzenberger, Neuroimaging labs (NIL) – PET, MRI, EEG, TMS & Chemical Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Email: rupert.lanzenberger@meduniwien.ac.at
References
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Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis

  • Gregor Gryglewski (a1), Pia Baldinger-Melich (a2), René Seiger (a3), Godber Mathis Godbersen (a1), Paul Michenthaler (a1), Manfred Klöbl (a4), Benjamin Spurny (a4), Alexander Kautzky (a1), Thomas Vanicek (a1), Siegfried Kasper (a5), Richard Frey (a6) and Rupert Lanzenberger (a7)...
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eLetters

Conclusions in Gryglewski et al. may not be warranted

Marco Chiesa, Consultant Psychiatrist and Visiting Professor, University College London
16 April 2019



A number of issues not addressed in this study require comment and clarification (1). First, the authors show that a significant increase in volumes in amygdala nuclei, hippocampus, putamen and cortical thickness occurred following a course of ECT in 12 patients. However, it is not stated whether these patients’ brain structures average size at baseline is significantly different to what we would expect to find in a healthy cohort, or what percentage of the sample fall below the norm. If this is not clarified, we need to understand why brain structure sizes that may fall within a normal distribution would require enlarging. Second, patients had two scans before ECT and the authors present the average of the two scans as baseline measures. The authors omit to say how different the measurements were between the two pre-ECT scans which would inform the reader as to the accuracy of each MRI reading. This is important since the same procedure was not employed at termination of treatment. Third, the authors attribute the increase in volume to a process of neurogenesis, which they consider a positive outcome. However, they do not seem to take into account the possibility that the neurogenesis may not be benign, but the result of the electrical insult inflicted to the brain, and that the proliferation and morphology of the newly created neurons may not be normal. Neurogenesis has also been observed to occur in similar areas of the brain following intake of Lithium and other mood stabilizers, but it was found that the number and morphology of the cells were abnormal, with “increasing growth of cone formation, leading to the spreading of the neuron and a shorter neuronal axon” (2). If such cellular proliferation in the areas connected with memory is a positive outcome, rather than a pathological reaction to a brain insult, then widespread memory and cognitive impairment found in a large percentage of ECT patients (3) needs explaining. Fourth, and related to the last point, there is no data presented on the incidence of adverse effects following ECT (disorientation, confusion, memory loss, concentration, impairment in abstract reasoning, overall level of cognitive functioning, docility, lethargy and apathy), which may impact on the ability to perform a post-treatment test. Finally, the authors bemoans the difficulty with recruiting “suitable patients” and ended up with a very small sample. In an era of anti-depressant induced treatment resistant depression (4, 5), I suspect that a fairly large number of patients in the University Clinic of Vienna would have met inclusion criteria. It is possible that other patients-related factors may have been involved in accounting for the very low sample size. In this respect, a wide gap between mainstream psychiatrists’ views and patients’ views regarding the usefulness of ECT has been revealed in a systematic review (6).

1. Gryglewski G, Baldinger-Melich P, Seiger R, Godbersen GM, Michenthaler P, Klöbl M, et al. Structural changes in amygdala nuclei, hippocampal subfields and cortical thickness following electroconvulsive therapy in treatment-resistant depression: longitudinal analysis. The British Journal of Psychiatry. 2018; 214(3): 159-67.

2. Lagace DC, Eisch AJ. Mood-stabilizing drugs: are their neuroprotective aspects clinically relevant? The Psychiatric clinics of North America. 2005; 28(2): 399-414.

3. Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson M. The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacology. 2007; 32(1): 244-54.

4. Fava GA. Can long-term treatment with antidepressant drugs worsen the course of depression? Journal of Clinical Psychiatry. 2003; 64: 123-33.

5. Fava GA, Offidani E. The mechanisms of tolerance in antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(7): 1593-602.

6. Rose D, Fleischmann P, Wykes T, Leese M, Bindman J. Patients' perspectives on electroconvulsive therapy: systematic review. BMJ. 2003; 326(7403): 1363.

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Conflict of interest: None declared

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