The Danish Neuropsychological Study of the Adverse Effects of ECT

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the adverse cognitive side-effects of electroconvulsive therapy (ECT). The second aim is to investigate the mechanisms of effect of ECT.

Detailed Description
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ECT has been the most effective treatment of depression for decades. Despite of this, neither the mechanism of action or side-effects are fully elucidated. The reason why some patients relapse shortly after remission is still not completely understood. Thus, there is a need to find predictors of the favourable clinical effect, relapse and side-effects. ECT is considered by professionals to be a safe procedure. Additionally, many patients do not consent to this treatment because they fear a permanent loss of memory or that they will contract a brain damage after the completed ECT series. Therefore, it is very important to examine whether ECT might have negative effects on the structure or function of the brain, using state of the art Magnetic Resonance Imaging (MRI) techniques. DANSECT is a prospective, observational follow-up study with the aim of examining why cognitive side-effects of ECT occur and potentially find predictors for whom they may affect by investigating the ECT-associated cognitive disturbances, structural brain changes and clinical outcomes. Second, DANSECT examines the mechanisms of effect of ECT. DANSECT comprises an ECT-group (30 patients) and a clinical control group (30 patients). The former consists of patients with depression receiving ECT, and the latter consists of matched patients with depression treated pharmacologically. The examinations will take place at three time-points; before, immediately after ECT or just before discharge, and 6 months after. DANSECT is a naturalistic clinical project. This means that the number of ECT sessions given to the patients in the ECT-group is up to the referring physician. The aim of DANSECT is to investigate the cognitive side-effects of ECT. Specifically, the research project aims to examine: Prevalence, extent and persistence of adverse cognitive effects following ECT. Associations between neuroimaging findings and cognitive changes following ECT. Predictors of adverse cognitive effects of ECT. Hypotheses: Consistency in autobiographical memories will be reduced over time in both study groups. However, the reduction will be significantly larger for the ECT patients after ECT compared to the control group. The group difference is expected to be present at both short-term and long-term. Autobiographical memory deterioration is expected to correlate with volumetric changes of the hippocampi. Processing speed, anterograde memory and executive functions will be temporarily deteriorated after ECT. The cognitive changes will correlate with volumetric brain changes and changes in structural connectivity. Baseline atrophy, age, years of education and cognitive reserve will predict the cognitive side-effects following ECT. Machine learning will reveal patterns and inference enabling the development of a predictive model of clinical and cognitive outcome after treatment with ECT, by combining neuropsychological tests, structural and functional neuroimaging (MRI) and other neurobiological measures. In addition, the aim of DANSECT is to investigate the mechanisms of effect of ECT. The secondary aims of the project are thus to examine: Clinical, biochemical and neurobiological predictors of response to ECT Clinical, biochemical and neurobiological predictors of relapse of depression after ECT Biochemical and neurobiological mechanisms of response to ECT Hypotheses: Smaller baseline hippocampal volume is associated with a larger post-pre reduction of depressive symptoms Thinner cortical thickness predicts better clinical improvement The cortisol trajectory before ECT is associated with clinical outcome Elevated peripheral baseline VEGF is associated with a larger post-pre reduction of depressive symptoms Baseline microRNA levels are associated with clinical outcome A higher baseline structural connectivity predicts better clinical improvement A larger post-ECT increase in hippocampal volume, cortical thickness, BDNF and VEGF predicts a lower risk of relapse within six months after an ECT series

Official Title
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The Danish Neuropsychological Study of the Adverse Effects of ECT

Conditions
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Depressive Disorder, Depression, Cognitive Dysfunction, Electroconvulsive Therapy

Intervention / Treatment
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* Other: Electroconvulsive therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-95 years admitted at the MHC Glostrup, MHC Amager or MHC Copenhagen (or other Mental Health Centres in the Capital Region) fulfilling the criteria for depression according to ICD-10 and where ECT is planned. must be able to give informed consent to participate in the study Exclusion Criteria: Schizophrenia or any other psychotic disorder except for psychotic depression Dependency syndrome according to ICD-10. Severe somatic or neurological condition (e.g. stroke) confounding results Head trauma resulting in unconsciousness for more than 5 minutes Severe psychotic symptoms or suicide impulses making transportation hazardous Contraindications against MRI Pregnancy Maintenance ECT or ECT received during the last 6 months Any form of compulsory treatment Subjects who do not consent to be informed of incidental findings that could have healthcare implications will not be scanned and can thus not be included

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ECT<br>Group of patients receiving ECT during their hospitalization. | Other: Electroconvulsive therapy<br>* Electroconvulsive therapy is a procedure, done under general anesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. Repeated as deemed needed by the patients' doctor. Typically prescribed 10 times (3 times pr week)<br>|
| Non-ECT<br>Group of patients not receiving ECT during their hospitalization. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Columbia Autobiographical Memory Interview - Short Form | Measures consistency in autobiographical memories over time. Scoring: Minimum: 0. Maximum: 60. A higher score means a better cognitive performance. | at baseline (before ECT series) | 
| Columbia Autobiographical Memory Interview - Short Form | Measures consistency in autobiographical memories over time. Scoring: Minimum: 0. Maximum: 60. A higher score means a better cognitive performance. | at 5 (+/- 2) days after completion of the ECT series | 
| Columbia Autobiographical Memory Interview - Short Form | Measures consistency in autobiographical memories over time. Scoring: Minimum: 0. Maximum: 60. A higher score means a better cognitive performance. | at follow-up (6 (+/-2) months after the ECT series | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale | Hamilton Depression Rating Scale 6-item. Scoring: Minimum: 0. Maximum: 22. A higher score means more symptom severity. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| The Screen for Cognitive Impairment for Psychiatry | Screening tool to measure cognitive performance across several cognitive domains. Scoring: Minimum 0. Maximum: Unlimited. A higher score means a better cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Reys complex figure task | Measures visuospatial, constructional, executive and anterograde memory abilities. Scoring: Minimum: 0. Maximum: 36. A higher score means a better cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Trail Making Test A | Measures psychomotor speed. Scoring: Minimum:0. Maximum: Unlimited. A higher score means a worse cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Trail Making Test B | Measures complex psychomotor speed / executive function. Scoring: Minimum:0. Maximum: Unlimited. A higher score means a worse cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Digit span (WAIS-IV) | Measures attention span (forwards) and working memory (backwards). Scoring: Minimum: 0. Maximum: 16. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Five Point Test | Measures spatial fluency / problem solving. Scoring: Minimum: 0. Maximum: Unlimited. A higher score means a better cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Color-Word Interference Test (D-KEFS) | Measures psychomotor speed, meantal flexibility and set-shifting. Scoring: Minimum: 0. Maximum: Unlimited. A higher score means a worse cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Symbol Digit Modalities Test | Measures psychomotor speed. Scoring: Minimum: 0. Maximum: Unlimited. A higher score means a worse cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Vividness of Visual Imagery Questionnaire - Danish version | Measures subjective experience of the vividness of ones mental visual imagery. Scoring: Minimum: 16. Maximum: 80. A higher score means more vividly experienced mental imagery. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Vocabulary (WAIS-IV) | Measures vocabulary and serves as an estimate of premorbid intellectual ability. Scoring: Minimum: 0. Maximum: 57. A higher score means a better vocabulary. | at one time point: at 5 (+/- 2) days after completion of the ECT series | 
| Cognitive complaints in bipolar disorder rating assessment | Self-report of experienced cognitive difficulties. Scoring: Minimum: 0. Maximum: 48. A higher score means more symptom severity. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Squire Subjective Memory Questionnaire | Self-report of experienced memory difficulties. Scoring: Minimum: -72. Maximum: +72. A higher score means a better cognitive function. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| Paired Associates Learning (CANTAB) | Visuospatial pattern localization. Scoring: Minimum 0. Maximum: Unlimited. A higher score (errors) means a worse cognitive performance. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 
| WHO-5 | Self-report of well-being in the last 14 days. Scoring: Minimum: 0. Maximum: 25. A higher score means a better experience of well-being. | at 3 time points: at baseline (before ECT series), at 5 (+/- 2) days after completion of the ECT series, at follow-up (6 (+/-2) months after the ECT series) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic Resonance Imaging, Hippocampus, Depression, Electroconvulsive therapy, Brain-Derived Neurotrophic Factor, Autobiographical memory, Cognitive side-effects