Neurobiological Markers of Treatment Response for Anxiety and OCD

Study Overview
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Brief Summary
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Obsessive-compulsive disorder (OCD) and anxiety disorders are common and debilitating conditions which are often chronic when treatment is not provided. International guidelines recommend cognitive behavioral therapy (CBT) as the first-line treatment, and research has shown that CBT can be delivered over a concentrated period of time. The Bergen 4-Day Treatment (B4DT) is an exposure-based treatment which is delivered over four consecutive days. B4DT has been shown to induce rapid and long-lasting remission in around 70% of patients. This provides a platform for studying psychological and neurobiological changes associated with treatment response and non-response. The present study will investigate longitudinal changes in psychological measures and DNA methylation in patients who receive the B4DT, as well as a subset will also undergo multimodal brain imaging.

Detailed Description
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The primary study will include 500 OCD patients who will receive the B4DT. Symptom severity will be prospectively measured before treatment, approximately 10 days after treatment and three months after treatment. Saliva samples will be collected for later extraction of DNA methylation during the first day of treatment, the last day of treatment, and three months after treatment. A substudy will use multimodal magnetic resonance imaging (MRI) before treatment, approximately 10 days after treatment and three months after treatment. The substudy will also 100 patients with social anxiety disorder or panic disorder for DNA methylation and MRI, as well as 50 healthy controls for MRI. Clinical data will be collected from a consent-based quality register (Kvalitetsregister for konsentrerte behandlingsformat). The aim of the study is to investigate changes in DNA methylation as well as functional and structural brain networks that occur in patients undergoing B4DT, and to correlate these changes with immediate and long-term response to treatment.

Official Title
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Neurobiological Markers of Treatment Response for Anxiety and OCD

Conditions
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Obsessive-Compulsive Disorder, Social Anxiety Disorder, Panic Disorder

Intervention / Treatment
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* Behavioral: Bergen 4-Day Treatment (B4DT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with obsessive-compulsive disorder, panic disorder or social anxiety disorder using DSM-5 criteria Referred to National Clinic for 4-Day Treatment, Haukeland University Hospital, Bergen, Norway Consented to participate in the Kvalitetsregister for konsentrerte behandlingsformat Exclusion Criteria: Suicidal, ongoing mania, primary eating disorder, intellectual disability, ongoing psychosis, ongoing substance abuse For MRI substudy: Inclusion Criteria: - For the healthy controls, no previous or current psychiatric disorders as detected by the Mini International Neuropsychiatric Interview (MINI) Exclusion Criteria: - MRI incompatibility (e.g. pregnancy, metal implants)

Ages Eligible for Study
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Minimum Age: 16 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with obsessive-compulsive, social anxiety or panic disorder<br>Patients with obsessive-compulsive disorder. The MRI substudy will also include patients with social anxiety or panic disorder | Behavioral: Bergen 4-Day Treatment (B4DT)<br>* A concentrated and exposure-based psychological treatment over four consecutive days<br>|
| For MRI substudy: Healthy controls<br>Healthy controls demographically matched to the patient group on age, sex and years of education | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Symptom severity of obsessive-compulsive disorder | Before treatment | 
| Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Symptom severity of obsessive-compulsive disorder | approximately 10 days after treatment | 
| Yale-Brown Obsessive Compulsive Scale (Y-BOCS) | Symptom severity of obsessive-compulsive disorder | three months after treatment | 
| Panic Disorder Severity Scale (PDSS) | Symptom severity of panic disorder | Before treatment | 
| Panic Disorder Severity Scale (PDSS) | Symptom severity of panic disorder | approximately 10 days after treatment | 
| Panic Disorder Severity Scale (PDSS) | Symptom severity of panic disorder | three months after treatment | 
| Liebowitz Social Anxiety Scale (LSAS) | Symptom severity of social anxiety disorder | Before treatment | 
| Liebowitz Social Anxiety Scale (LSAS) | Symptom severity of social anxiety disorder | approximately 10 days after treatment | 
| Liebowitz Social Anxiety Scale (LSAS) | Symptom severity of social anxiety disorder | three months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA Methylation | Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system | Before treatment | 
| DNA Methylation | Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system | approximately 10 days after treatment | 
| DNA Methylation | Samples of saliva will be collected for genome-wide methylation and profiling will be carried out using the Illumina Infinium MethylationEPIC BeadChip system | three months after treatment | 
| Magnetic Resonance Imaging | Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls | Before treatment | 
| Magnetic Resonance Imaging | Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls | approximately 10 days after treatment | 
| Magnetic Resonance Imaging | Brain functional and structural MRI will be collected for a subset of 100 OCD and 100 anxiety disorder patients as well as 50 healthy controls | three months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, epigenetics, genetics