Neurobiology of Sensory Phenomena in Obsessive-Compulsive Disorder

Study Overview
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Brief Summary
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The Research Domain Criteria (RDoC) approach seeks to address the neurobiological mechanisms of sensory symptoms in patients with obsessive-compulsive disorder (OCD) by investigating dimensional components of behavior that more closely align with brain circuitry. This project focuses on the dimensional symptom of sensory phenomena (SP), which are uncomfortable or aversive sensory experiences that drive repetitive behaviors in OCD, including not just right sensations, physical urges, and sensations of disgust. SP are very prevalent, occurring in 60-80% of OCD patients, and experienced as highly distressing. Unfortunately, SP are not well addressed by standard treatment approaches, which may be in part because their neurobiological mechanisms are not well understood. This project builds on our preliminary data to (1) investigate the neural mechanisms of SP in large OCD cohort showing the full range of SP severity and (2) probe for familial risk markers in unaffected siblings of patients. For Aim 1, SP will be measured in 100 OCD patients using the Sensory Phenomena Scale. Diffusion and fMRI data will be acquired during rest and fMRI tasks. In order to identify familial risk markers, Aim 2 will compare sensory phenomena and neural circuitry between OCD probands, 50 unaffected biological siblings of OCD patients, and 50 unrelated healthy controls without a family history of Axis 1 disorders.

Detailed Description
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This project investigates the neurobiological mechanisms of sensory symptoms in patients with obsessive-compulsive disorder (OCD) and their siblings using task-based fMRI, resting-state functional connectivity, and diffusion MRI approaches. OCD is a chronic disorder presenting a high public health burden. Treatment presents a particular challenge because OCD is extremely heterogeneous, with clusters of symptoms likely derived from differing neural etiologies.

Official Title
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Neurobiology of Sensory Phenomena in Obsessive-Compulsive Disorder

Conditions
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Obsessive Compulsive Disorder

Intervention / Treatment
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* Other: Tasked based functional MRI (fMRI)
* Other: Eye Tracking Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fluent (speaking and writing) in English Additional criteria for healthy controls (HC): Lifetime absence of major Axis I diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria Not taking psychotropic medications No first-degree biological relatives with OCD Additional criteria for siblings (SIB): First-degree biological sibling of a person with OCD Additional criteria for OCD patients: Diagnosis of OCD according to DSM-5 criteria. Exclusion Criteria: Current moderate or high suicidality as assessed through the Mini International Neuropsychiatric Interview (MINI) 7.0.2 suicidality module MRI contraindications such as claustrophobia, ferrous implants, braces, or pacemakers Major neurological illness (e.g., self-reported history of organic mental syndromes, head trauma, migraines, seizures, other Central Nervous System (CNS) disease, or other significant medical illness that would make participation unsafe or unfeasible) Positive urine toxicology or pregnancy test Any disability or health problem that prevents them from completing study procedures (e.g. back problems, severe carpal tunnel syndrome, impaired vision that is not corrected with glasses or contact lenses, etc.). Present diagnosis of alcohol use disorder or substance use disorder (moderate or severe) Present or previous diagnosis of psychosis, bipolar disorder, or major developmental disorder (autism spectrum disorder, intellectual developmental disorder) based on DSM-5 criteria.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OCD Proband<br>Healthy controls (HC, n=50) without a family history of OCD will be matched to SIB. | Other: Tasked based functional MRI (fMRI)<br>* 2-3 brief computer tasks while brain activity is being measured. The tasks performed will involve making button press responses to letters, numbers or shapes on the computer screen.<br>Other: Eye Tracking Device<br>* Camera aimed at eyes to record eye movements during tasks<br>|
| Active Comparator: OCD Siblings<br>Healthy controls (HC, n=50) without a family history of OCD will be matched to SIB. | Other: Tasked based functional MRI (fMRI)<br>* 2-3 brief computer tasks while brain activity is being measured. The tasks performed will involve making button press responses to letters, numbers or shapes on the computer screen.<br>Other: Eye Tracking Device<br>* Camera aimed at eyes to record eye movements during tasks<br>|
| Active Comparator: Healthy Controls<br>Healthy controls (HC, n=50) without a family history of OCD will be matched to SIB. | Other: Tasked based functional MRI (fMRI)<br>* 2-3 brief computer tasks while brain activity is being measured. The tasks performed will involve making button press responses to letters, numbers or shapes on the computer screen.<br>Other: Eye Tracking Device<br>* Camera aimed at eyes to record eye movements during tasks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activation in relation to sensory phenomena severity in patients with OCD | Statistical modeling using path analysis will test whether brain activation, functional connectivity, and diffusion measures predict Sensory Phenomena (SP) better than alternative models of predictive influence. | 4 Hours |