Mindfulness-Based Cognitive Therapy: Efficacy and fMRI-based Response Predictors in a Group of OCD Patients

Study Overview
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Brief Summary
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Obsessive-Compulsive Disorder (OCD) patients have a response rate of 50-60% to exposure and response prevention (ERP) therapy and SSRI antidepressants. Mindfulness-Based Cognitive Therapy (MBCT) consists of training the participant to non-react to negative thoughts and emotions. Applying MBCT to OCD patients may help them behave with equanimity in response to their obsessions, and therefore acknowledge them with the same attention and intention as they admit any other disturbing thought without reacting to it. MBCT has demonstrated effectiveness in major depression, but much less attention has been given to MBCT in OCD. ERP and MBCT, although sharing aspects like exposure, are based on different theoretic and therapeutic factors. EPR is based on a direct anxiety habituation process whereas MBCT trains a holistic manner of becoming familiarized with distressful thoughts and emotions while learning to develop a new relationship to them. Thus, MBCT may decrease anxiety indirectly through a major attention awareness and non-reactivity to thoughts and emotions. OCD is characterized by altered cortical-striatal-thalamic-cortical (CSTC) circuit and default mode network (DMN) connectivity when performing different tasks and during the resting state. It has been establish that the ventral CSTC circuit is mostly associated with emotional processing, while the dorsolateral aspect of the CSTC circuit is preferentially involved in cognitive processing. In this regard, we hypothesized that clinical amelioration will be accompanied by a re-establishment of functional connectivity within dorsolateral and DMN circuits, which will in turn be associated with improvement of certain neuropsychological processes. CSTC and DMN circuits have also shown to be sensitive to prolonged stress situations. Specifically, childhood trauma has been related to larger brain volumes and it has been associated with different OCD clinical subtypes. Aims: 1. To assess MBCT effectiveness in treatment non-naive OCD patients. 2. To study cognitive and neuropsychological characteristics that mediate or moderate MBCT response. 3. To examine the changes in cognitive, neuropsychological and neuroimaging patterns associated with an MBCT intervention. 4. To identify a brain biomarker for positive response to MBCT in non-naïve OCD patients. 5. To study cognitive, neuropsychological and early stress expousure mediators or moderators of functional changes in CSTC and DMN patterns in response to MBCT.

Official Title
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Mindfulness-Based Cognitive Therapy: Efficacy and fMRI-based Response Predictors in a Group of OCD Patients Non-responders to CBT

Conditions
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Obsessive-Compulsive Disorder

Intervention / Treatment
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* Behavioral: Mindfulness Based Intervention
* Drug: Treatment as Usual


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age frame: 18-50 years old. Principal Diagnosis: Obsessive compulsive disorder. Severity of OCD symptoms: between mild (Y-BOCS=9) and severe (Y-BOCS=32) Previous structured CBT or EPR, either in group or individual format, between 10 to 20 sessions. A maximum of three different pharmacological strategies. Minimum of IQ 85 measured by Vocabulary subtest (WAIS-IV). Minimum level of schooling: 14 years. To sign the informant consent. Exclusion Criteria: Organic pathology and/or neurological disorders such as brain injury or epilepsy. Comorbidity with: Mental Retardation, previous or current substance abuse, psychotic disorders, bipolar disorder. Other affective and/or anxiety disorders will not be an exclusion criteria if OCD is considered the primary diagnosis. Recent suicide attempt/active suicidality Previous completion of an MBCT course (≥ 8 weeks)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mindfulness Based Intervention<br>Mindfulness-based cognitive therapy (MBCT), adjusted to OCD patients, will be applied in 10 weekly sessions of 2 hours followed by an extra session 4 weeks later. The treatment will be applied in a group format of 10 to 12 patients. These patients will be also attending to their regular psychiatric visits for medication control. | Behavioral: Mindfulness Based Intervention<br>* The mindfulness based intervention protocol used in this project is adapted from the original and validated MBCT program for depression (Segal, Williams & Teasdale, 2002). Two more sessions, focused on obsessive symptoms specfic to each participant, will be included. Those two sessions will be adapted from the manual The Mindfulness Workbook for OCD (Hershfield and Corboy, 2013).<br>* Other names: MBCT;Drug: Treatment as Usual<br>* The psychiatric referee will follow OCD guidelines modifying or potentiating drug treatments if needed.<br>* Other names: TAU;|
| Active Comparator: Treatment as Usual (TAU)<br>Patients will be attending to their regular psychiatric visits during the whole trial period. | Drug: Treatment as Usual<br>* The psychiatric referee will follow OCD guidelines modifying or potentiating drug treatments if needed.<br>* Other names: TAU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Y-BOCS: | • Clinical version of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) the severity and the checklist. | Baseline and at 14 weeks and at 6 months post-treatment | 
| Change in OCI-R: | • Obsessive-Compulsive Inventory-Revised (OCI-R) assessing 6 dimensions (Washing, Checking, Ordering, Obsessing, Hoarding and Neutralizing). | Baseline, at 14 weeks and at 6 months post-treatment | 
| Change in OBQ-44: | • Obsessive Beliefs Questionnaire-44 (OBQ-44), a measure of three OCD-related belief domains (Perfectionism/Certainty, Importance/Control of thoughts, and Responsibility/Threat estimation). | Baseline and at 14 weeks | 
| Changes in functional brain circuits: | • Functional Magnetic Resonance Imaging: Resting state and during task performance (Autobiographical memory + N-Back) and self-reference. | Baseline and at 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anxiety: | • Anxiety Sensitivity Index (ASI-3) | Baseline and at 14 weeks | 
| Change in mood from baseline: | • The Beck Depression Inventory (BDI-II) | Baseline, at 14 weeks and at 6 months post-treatment | 
| Change in positive and negative affect: | • Positive and Negative Affect trait (PANAS) | Baseline and at 14 weeks | 
| Impact of current life events: | • Perceived Stress Scale (PSS) | Baseline, 14 weeks and at 6 months post-treatment | 
| Impact of past stressful life events: | • Childhood Trauma Questionnaire (CTQ) | Baseline | 
| Change in attentional domains: | • Conners' Continuous Performance Test II : CPT-II | Baseline and at 14 weeks | 
| Change in executive Functioning/Cognitive flexibility: | • Wisconsin Card Sorting Test: WCST | Baseline and at 14 weeks | 
| Autobiographical memories: | • Autobiographic Memory Task: 10 selected emotions (5 negative and 5 positive). | Baseline | 
| Change in verbal fluency: | • Phonetic Fluency: PMR (Spanish version of the FAS) | Baseline, 14 weeks and at 6 months post-treatment | 
| Speech analysis: | • Word Task: Assessment of language fluency and thought content using a list of 10 seed words from the Spanish adaptation of the ANEW (Affective Norms for English Words) in terms of positive and negative valance and different degrees of arousal. | Baseline | 
| Thought content: | • ES-Questionnaire, designed by Drs. J. Andrews-Hanna and M. López-Solà (research collaborators of the project) from the USA. It is based on 23 questions that examines the thought content from the patient before, during and after the treatment. | Baseline, each week during the treatment period (10 sessions) and post-treatment | 
| Change in Quality of Life: | • Multicultural Quality of Life Index (MQLI). | Baseline, 14 weeks and at 6 months post-treatment | 
| Change in Mindfulness variables: | • Mindfulness measures include: The Five Facet Mindfulness Questionnaire (FFMQ), used to measure the five constructs central to mindfulness (Observing, Describing, Acting with Awareness, Non-judgment of Inner Experience, and Non-reactivity to Inner Experience). | Baseline, 14 weeks and at 6 months post-treatment | 
| Change in Rumination: | • Ruminative Responses Scale (RRS) to measure the degree and type of thought thinking. | Baseline, 14 weeks and at 6 months post-treatment | 
| Treatment expectancy: | • Credibility Expectancy Questionnaire (CEQ). | Baseline | 
| Changes in structural brain regions: | • Structural acquisition: T13D | Baseline and at 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obsessive-Compulsive Disorder, Mindfulness Based Intervention, Cognitive-Behavioral Therapy, Functional Magnetic Resonance Imaging, Neuropsychology, Childhood Maltreatment