Mechanisms of Mindfulness-Based Cognitive Therapy in the Treatment of Recurrent Major Depressive Disorder

Study Overview
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Brief Summary
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The primary purpose of this study is to investigate neural mechanisms and predictors of treatment outcome in Mindfulness-Based Cognitive Therapy (MBCT) for recurrent Major Depressive Disorder.

Detailed Description
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AIM AND HYPOTHESES The primary aim is to investigate treatment mechanisms of MBCT and markers of relapse risk. Controlled design: First, we aim to first investigate the effect of treatment on clinical outcomes in the controlled design post treatment and at 3 months follow up. Second, we will run mediation analyses of hypothesized mechanisms (increased mindfulness skills, decentering, interoceptive and decreased rumination, and change in neural connectivity in a priori networks), and finally check for moderating influences of vulnerability markers (childhood trauma, no. episodes of depression and residual symptoms). Prospective design: We aim to investigate predictors of relapse risk at 12 month follow treatment using i) baseline markers and ii) mechanism outcomes that change significantly due to treatment, and iii) check for moderating influences of vulnerability markers

Official Title
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Neural, Molecular and Psychological Mechanisms and Predictors of Treatment Response to Mindfulness-based Cognitive Therapy in the Treatment of Recurrent Major Depressive Disorder

Conditions
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Major Depressive Disorder, Recurrent

Intervention / Treatment
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* Behavioral: MBCT
* Other: TAU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years Meeting DSM-IV criteria for a history of recurrent Major Depressive Disorder (MDD) with or without a current episode of depression Recurrent MDD evaluated a being the primary disorder. Danish literacy Exclusion Criteria: A history of schizophrenia, schizoaffective disorder, bipolar disorder, current severe substance abuse, organic mental disorder, current/past psychosis, pervasive developmental delay, persistent antisocial behaviour, persistent self-injury requiring clinical management/therapy Formal concurrent psychotherapy Previous Mindfulness-Based Cognitive Therapy/Mindfulness-Based Stress Reduction Anti-psychotic medication and benzodiazepines Standard exclusion criteria for undergoing magnetic resonance imaging (MRI) procedures for research purposes, i.e., claustrophobia, pregnancy, cardiac pacemaker, prosthetic heart valve, neurostimulator, implanted pumps, cochlear implants, non-MR-compatible implants or devices.

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised to Mindfulness-based cognitive therapy plus treatment as usual, or treatment as usual.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBCT + TAU<br>Mindfulness-based Cognitive Therapy (MBCT) a 8 week group based intervention delivered according to the protocol by Segal, Williams and Teasdale (2013) plus treatment as usual (TAU) . TAU is restricted to antidepressant medication and no psychological therapy. | Behavioral: MBCT<br>* Mindfulness-Based Cognitive Therapy (MBCT) is an 8 week manualised group intervention. MBCT will be delivered according to the manual by Segal, Williams & Teasdale (2013).<br>Other: TAU<br>* Treatment as usual (TAU)<br>|
| Other: TAU<br>Treatment as Usual (TAU). TAU is restricted to antidepressant medication and no psychological therapy. | Other: TAU<br>* Treatment as usual (TAU)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neural connectivity | Neural connectivity will be measured with functional magnetic resonance (fMRI). Selected a priory networks for seed-based analyses: Default mode Network and Salience Network | Baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mindfulness skills | Five Factor Mindfulness Questionnaire (FFMQ) | Baseline and 8 weeks | 
| Change in decentering | Experiences Questionaire (EQ) | Baseline and 8 weeks | 
| Change in rumination | Rumination Response Scale (RRS) | Baseline and 8 weeks | 
| Change in emotional processing bias | Facial Expression Recognition task (FERT) | Baseline and 8 weeks | 
| Change in interoceptive awareness | Multidimensional Assessment of Interoceptive Awareness (MAIA) | Baseline and 8 weeks | 
| Change in perceived stress | Perceived Stress Scale (PSS) | Baseline and 8 weeks | 
| Time to relapse or recurrence of depression | Structured clinical interview for DSM-IV | 12 months follow up | 
| Change in depressive symptoms | Quick Inventory for Depressive Symptomology (QIDS-SR) | Baseline and 8 weeks | 
| Change in interleukin gene expression | IL-1, IL-2, IL-4,IL-6, IL-8, IL-10, IL-12p70, IL-13, | Baseline and 8 weeks | 
| Change in interleukin protein expression | IL-1, IL-2, IL-4,IL-6, IL-8, IL-10, IL-12p70, IL-13, | Baseline and 8 weeks | 
| Change in gene expression of norepinephrine transporter | Norepinephrine transporter (NET) | Baseline and 8 weeks | 
| Change in gene expression of glutamate receptor | Glutamate receptor (GRM7) | Baseline and 8 weeks | 
| Change in gene expression of TNF | Change in gene expression of tumor necrosis factor (previous nomenclature TNF-alfa) | Baseline and 8 weeks | 
| Change in protein expression of tumor necrosis factor | Tumor necrosis factor | Baseline and 8 weeks | 
| cRP expression | c reactive protein expression | Baseline and 8 weeks | 
| Change in NF-kB gene expression | Nuclear factor kappa-light-chain-enhancer of activated B cells gene expression | Baseline and 8 weeks | 
| Change in NF-kB protein expression | Nuclear factor kappa-light-chain-enhancer of activated B cells protein expression | Baseline and 8 weeks | 
| Change in INFG gene expression | Interferon gamma gene expresison | Baseline and 8 weeks | 
| Change in Interferon gamma protein expression | Interferon gamma protein expresison | Baseline and 8 weeks | 
| Mitochondrial DNA Copy Number | Copy number is assessed using quantitative real-time-PCR | Baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mindfulness-Based Cognitive Therapy, Neural, psychological and molecular mechanisms