Inflammation and Electroconvulsive Therapy

Study Overview
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Brief Summary
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The purpose of this study is to explore whether electroconvulsive therapy (ECT) accidentally leads to a side effect of brain inflammation. Patients with treatment resistant depression who are planning to take ECT will be subsequently approached to participate in the study.

Detailed Description
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The first scan will take place before the first ECT session. The second scan will occur after a minimum of six ECT sessions (average 2.5 weeks). Secondary measures will include mood symptom severity, neurocognitive measures, peripheral inflammatory markers and TSPO genotype. The hypothesis is that neuroinflammation will be increased by ECT. There will be no alterations to standard care of depressed patients due to participation in the study.

Official Title
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Does Electroconvulsive Therapy Cause Neuroinflammation? An [18F]FEPPA Positron Emission Tomography Study in Treatment Resistant Depression

Conditions
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Major Depressive Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stable physical health diagnosis of non-psychotic, non-catatonic, major depressive disorder, either unipolar or bipolar and a non-response to at least three clinical trials at appropriate dose of antidepressant medication from at least three different pharmacological classes at least a 17 on the17-item HDRS despite taking antidepressant treatment prior to ECT have not received ECT within the last 12 weeks Exclusion Criteria: currently pregnant current substance abuse or dependence neurological or unstable medical illness use of anti-inflammatory drugs within the past month diazepam or other benzodiazepine use within the past month, except for lorazepam and clonazepam

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 and Treatment Resistant Depression<br>Subjects will be those with diagnosis of major depressive disorder that have not responded to many different treatments and who are planning to take electroconvulsive therapy (ECT). This group will receive two [18F]FEPPA PET scans, one baseline and one after an average of 2.5 weeks of ECT treatments. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in translocator protein distribution volume (TSPO Vt) measured by [18F]FEPPA PET | Participants will have one [18F]FEPPA PET scan before they start ECT and a second PET scan on average after 2.5 weeks of ECT | Baseline scan and a second PET scan after an expected average time of 2.5 weeks of ECT treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-item Hamilton Depression Rating Scale (HDRS) | Scores on the 17-item HDRS will be taken at the time of the PET scan (baseline and post-ECT) to assess whether the magnitude of change in TSPO distribution volume is associated with changes in symptom severity. | Baseline and after average 2.5 weeks of ECT treatment | 
| Neurocognitive Battery | Neurocognitive measures will be take at baseline and post-ECT to assess whether TSPO Vt is related to neurocognitive function. Neurocognitive battery includes: Autobiographical Memory Interview-Short Form (AMI-SF) Rey Auditory Verbal Learning Test (RAVLT) Wisconsin Card Sorting Test Comprehensive Trail Making Test Weschler Adult Intelligence Scale-Digit Symbol Subtest Stroop Color and Word Test Brief Visuospatial Memory Test Boston Naming Test Judgement of Line Orientation Weschler Test of Adult Reading | Baseline and after average 2.5 to 5 weeks of ECT treatment | 
| Peripheral Inflammatory Markers | To explore whether peripheral and central inflammation are related markers of peripheral inflammation (TNF-alpha, IL-6, CRP and IL-1beta) will be measured and correlated to brain TSPO Vt. | Baseline and after average 2.5 to 5 weeks of ECT treatment |