Cerebral Neuroinflammation During Major Depressive Episode

Study Overview
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Brief Summary
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the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the [18 F ] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to treatment in patients with MDD. If this assumptions are validated, then this study will enable a better understanding of the neuroinflammatory processes. This breakthrough could have a long term therapeutic impact, helping to target more specifically antidepressant drugs with anti-inflammatory action and / or drugs targeting neuroinflammation.

Detailed Description
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The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the [18F] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.

Official Title
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Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.

Conditions
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Depressive Disorder

Intervention / Treatment
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* Diagnostic Test: Cerebral neuroinflammation evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for all groups: Written agreement for participation Able to understand instructions and information data Inclusion criteria for the experimental group: Responding to MDD criteria (DSM-5) MADRS score> 20 Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least a week and plasma levels within the therapeutic range) Inclusion criteria for the pathological control group : Having met MDD criteria (DSM-5) In remission for 8 weeks according to the DSM-5 MADRS score <10 Treated with antidepressants (unchanged dosage for at least week) Inclusion criteria for the control group : Without any neurological or psychiatric previous disorder CRPus < 5mg/L Exclusion criteria for all groups: Patients without public insurance regime. Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand). Pregnant and breastfeeding women Persons deprived of liberty by judicial or administrative decision People hospitalized without consent, or subject to legal protection Persons unable to consent Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder (PCL-S> ou =45), known system pathology Patients with a history of stroke Patients with an acute infectious disease Patients with chronic inflammatory pathology. Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or diazepam Exclusion criteria for control group: No significant psychiatric or somatic history. No psychotropic treatment Suicidal risk (C-SSRS) Anxiety Disorders (MINI)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerebral neuroinflammation evaluation<br>The density of TSPO (which is an inflammation maker) is evaluated by the tracer's brain distribution volume ([18F] DPA-714). | Diagnostic Test: Cerebral neuroinflammation evaluation<br>* Pet scan following an injection of the radiotracer ([18F]DPA-714), to evaluate the neuroinflammation. MRI to evaluate functional and structural integrities. Blood test to analyze various inflammation marker (IL-6, Tumor Necrosis Factor (TNF) alpha, CRPus, and TSPO). And psychological scales to assess the depressive symptoms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| distribution pattern of neuroinflammation in Positron Emission Tomography (PET) data | Assessed between patients with MDD (experimental group), patients who have had a MDD and being in remission for at least 8 weeks, still treated with antidepressants, matched in age and gender with the experimental group (pathological control group) and control subjects, matched in gender and age with both patients' groups (control group). | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| distribution pattern of neuroinflammation in PET data across all groups | Across all groups (i.e. experimental group, pathological control group and control group). | Day 7 | 
| patients with depressive symptoms and neuroinflammation (i.e. PET data). | Depressive symptoms are assessed by the Montgomery and Asberg Depression Scale (MADRS) and the Columbia-Suicide severity rating scale (CSSRS). Correlation across all groups (experimental group, pathological control group and control group). | Day 7 | 
| patients with neuroinflammation (i.e. PET analysis) and MRI parameters for functional and structural integrities. | Correlation across all groups (experimental group, pathological control group and control group). | Day 7 | 
| patients with neuroinflammation (i.e. PET analysis) and biological markers of neuroinflammation (i.e. cytokines). | Correlation across all groups (experimental group, pathological control group and control group). | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depressive disorder, Treatment Resistant Depression, [18 F ] DPA- 714, PET, MRI, Inflammation