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

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder, Recurrent
• Intervention / Treatment: Behavioral: MBCT; Other: TAU

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age above 18 years
2. Meeting DSM-IV criteria for a history of recurrent Major Depressive Disorder (MDD) with or without a current episode of depression
3. Recurrent MDD evaluated a being the primary disorder.
4. Danish literacy

Exclusion Criteria:

1. 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
2. Formal concurrent psychotherapy
3. Previous Mindfulness-Based Cognitive Therapy/Mindfulness-Based Stress Reduction
4. Anti-psychotic medication and benzodiazepines
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MBCT + TAU; 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; 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).; Other: TAU; Treatment as usual (TAU)
Other: TAU; Treatment as Usual (TAU). TAU is restricted to antidepressant medication and no psychological therapy.	Other: TAU; Treatment as usual (TAU)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI BOLD secondary and whole brain analyses	fMRI BOLD whole brain analyses (data-driven) and secondary subcortical seed-based analyses: As seeds we preselect hippocampus, the amygdala and striatum	Baseline and 8 weeks
Global Gene expression with focus on genes involved in mitochondrial function, the respiratory chain.	HG-U133 Plus 2.0 GeneChip (Affymetrix)	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Harvard Medical School (HMS and HSDM); University of Oxford; VIA University College; University of York
• Investigators: Principal Investigator: Anne Maj van der Velden, Msc, Department of Clinical Medicine, Aarhus University

Publications and helpful links

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: September 8, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Mindfulness-Based Cognitive Therapy; Neural, psychological and molecular mechanisms
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Disease Attributes; Depression; Depressive Disorder; Recurrence; Depressive Disorder, Major
• Other Study ID Numbers: 314 #2016-051-000001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No