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On electroconvulsive therapy in depression: Clinical, cognitive and neurobiological aspects
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Psychiatry.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Electroconvulsive therapy (ECT) is used worldwide to treat severe mental disorders. The most common mental disorder, and the third leading cause of disease burden in the world is depression. The clinical efficacy of ECT for severe depression is well-established. However, both the pathophysiology of depression and the mechanism of action of ECT remain elusive.

The main aims of this thesis are to address the following issues: 1) the use and practice of ECT in Sweden has not been systematically evaluated since 1975, 2) cognitive side-effects (memory disturbances) are a major concern with ECT and 3) the mechanism of action of ECT remain elusive. The neurobiological aspects of ECT focus on two hypotheses. First, the recent years´ preclinical studies that have provided evidence that ECT induces hippocampal cell proliferation, including neurogenesis. Second, that enhanced functional inhibition of neuronal activity is a key feature.

Current use and practice of ECT in Sweden (paper I) is based on data from the national quality register for ECT, the mandatory patient register of the National Board of Health and Welfare and a survey. Treated person rate (TPR) in Sweden 2013 was found to be 41 individuals / 100 000, and thus unchanged since the latest systematic investigation in Sweden 1975. In more than 70% of treatment series the indication was a depressive episode. The selection of patients for ECT and treatment technique in Sweden was similar to that in other western countries, but the consent procedure and the involvement of nurses and nursing assistants in the delivery of ECT differ. Data also shows that there is room for improvement in both the specificity of use and availability of ECT.

The second study in this thesis is a longitudinal observational trial where 12 (paper II and III) and 14 (paper IV) patients with depression referred for ECT were investigated. Patients underwent a 3 T MRI structural scanning and DSC-MRI perfusion, a neuropsychological test battery and clinical ratings before ECT, within one to two weeks after ECT and after 6 and 12 months.  In line with preclinical findings and the plasticity hypothesis of mechanism of action of ECT, the hippocampal volume increased after ECT in patients with depression. However, this increase was transient and returned to baseline levels within 6 months. No correlation was found between volumetric changes and clinical effect or cognitive outcome. Instead our results suggested an association to the number of treatments, without relation to the side of stimulation. A right-sided decrease in frontal blood flow distinguished remission from non-remission after ECT. There were significant impairments in verbal episodic memory and verbal fluency within one week after ending the ECT course, but these impairments were transient and no persistent cognitive impairments were seen during the follow-up.

In summary, this thesis present the first update on the use and practice of ECT in Sweden in the last 40 years as well as a pioneering MRI-study on the hippocampal volume increase in the treatment of depression with ECT. Supportive to earlier findings we also found the cognitive side-effects that are measurable after ECT to be transient. Furthermore, we found that a decreased frontal blood flow is of importance for the anti-depressive response to ECT.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 68 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1468
Keyword [en]
ECT, electroconvulsive therapy, depression, MRI, cognitive, hippocampus
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:liu:diva-121458DOI: 10.3384/diss.diva-121458ISBN: 978-91-7519-026-6 (print)OAI: oai:DiVA.org:liu-121458DiVA: diva2:855392
Public defence
2015-10-16, Berzeliussalen, Ingång 64/65, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2016-04-06Bibliographically approved
List of papers
1. Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT
Open this publication in new window or tab >>Electroconvulsive Therapy in Sweden 2013: Data From the National Quality Register for ECT
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2015 (English)In: The Journal of ECT, ISSN 1095-0680, Vol. 31, no 4, 263-267 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: The use of electroconvulsive therapy (ECT) varies across countries. The aim of this study was to describe and explore the use of ECT in Sweden in 2013.

Methods: The Swedish mandatory patient register of the National Board of Health and Welfare includes information on diagnoses and treatments, including ECT. All 56 hospitals that provide ECT in Sweden also report to the nonmandatory national quality register for ECT, which contains information on patient and treatment characteristics. In this study, we combined data from both registers. In addition, all hospitals responded to a survey concerning equipment and organization of ECT.

Results: We identified 3972 unique patients who received ECT in Sweden in 2013. This translates into 41 ECT-treated individuals per 100,000 inhabitants. Of these patients, 85% opted to participate in the quality register. The median age was 55 years (range, 15-94 years), and 63% were women. The indication was depression in 78% of the treatment series. Of 4 711 hospitalized patients with severe depression, 38% received ECT. The median number of treatments per index series was 7. Unilateral treatment was used in 86% of the series.

Conclusions: In Sweden, ECT is used at a relatively high rate as compared with other western countries, and the rate was unchanged from the last survey in 1975. However, there is room for improvement in the specificity of use and availability of ECT for disorders where ECT is considered a first-line treatment.

Place, publisher, year, edition, pages
Wolters Kluwer, 2015
Keyword
electroconvulsive therapy, depression, epidemiology
National Category
Psychiatry Neurology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-121477 (URN)10.1097/YCT.0000000000000243 (DOI)000365687200013 ()25973769 (PubMedID)
Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2016-05-04Bibliographically approved
2. Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study
Open this publication in new window or tab >>Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study
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2010 (English)In: JOURNAL OF ECT, ISSN 1095-0680, Vol. 26, no 1, 62-67 p.Article in journal (Refereed) Published
Abstract [en]

Background: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression.

Methods: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated.

Results: The left as well as the right hippocampal volume increased significantly after ECT.

Conclusions: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.

Keyword
ECT, depression, hippocampus, MRI, neurogenesis
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:liu:diva-54702 (URN)10.1097/YCT.0b013e3181a95da8 (DOI)000275571000017 ()
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2015-09-22Bibliographically approved
3. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression
Open this publication in new window or tab >>Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression
2014 (English)In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 129, no 4, 303-311 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome.

METHOD:

Clinical and cognitive outcome in 12 in-patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery-Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI.

RESULTS:

Hippocampal volume returned to baseline during the follow-up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT.

CONCLUSION:

The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome.

Place, publisher, year, edition, pages
United States: Wiley-Blackwell, 2014
Keyword
hippocampus, magnetic resonance imaging, depression, electroconvulsive therapy, cognition, longitudinal
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:liu:diva-104959 (URN)10.1111/acps.12150 (DOI)000332684900006 ()23745780 (PubMedID)
Available from: 2014-03-04 Created: 2014-03-04 Last updated: 2017-12-05
4. Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI study
Open this publication in new window or tab >>Relative decrease of frontal blood flow after electroconvulsive therapy in depression distinguishes remission: a perfusion MRI study
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Understanding electroconvulsive therapy (ECT) is of importance not only for optimizing treatment, but could also provide important information about key features of the healing process in depression. Enhanced inhibition (the anticonvulsant hypothesis) is one of several suggested mechanisms of action of ECT. Earlier studies on cerebral blood flow during ECT have given diverging results. Our aim was to study changes in cerebral blood flow in depression treated with ECT and their relation to treatment outcome.

Methods: We obtained MRI scans in 14 depressed subjects referred for ECT. Cerebral blood flow (CBF) was measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) within 1 week before and 2 weeks after a course of ECT. The relative CBF was calculated from mean values in predefined regions of interest in relation to the mean value in the whole brain.

Results: A significant relative CBF increase in the occipital region (p < 0.05) and a significant relative decrease in the right lateral temporal lobe (p < 0.05) were found in the entire study group. A significant decrease in the right frontal lobe, with a significant anteriorposterior and right-left gradient shift in relative CBF, was a distinguishing feature in patients with ECT-induced remission (n = 8).

Limitations: This observational study is limited by the risk of random bias and its low number of participants.

Conclusions: Our results suggest that a decreased relative blood flow in frontal regions may be a hallmark of treatment efficacy in depression treated with ECT.

National Category
Public Health, Global Health, Social Medicine and Epidemiology Psychiatry Neurology
Identifiers
urn:nbn:se:liu:diva-121478 (URN)
Available from: 2015-09-21 Created: 2015-09-21 Last updated: 2015-09-21Bibliographically approved

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