An fMRI Study Investigating the Effects of Acute D-cycloserine Administration on Brain Activations and Cognitive Functioning in Spider Phobia.
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Phobias
- Sponsor
- University of Kansas Medical Center
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- fMRI Brain Activations During Symptom Provocation
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The research team hopes to use brain imaging and mental testing to learn more about specific phobias and the treatment of phobia. When given directly prior to therapy sessions, D-cycloserine has been shown to enhance the effects of therapy. This study hopes to identify reasons why D-cycloserine has this effect by measuring brain activity.
Detailed Description
Exposure and Response Prevention (ERP) therapy has become the treatment of choice for specific phobias. ERP involves systematic and repeated exposure to a feared or anxiety-provoking stimulus, leading to habituation and extinction of the fear response. Animal models of fear extinction have shown that acute administration of D-cycloserine (DCS) prior to exposure to a feared stimulus enhances extinction of that fear. A recent study in human subjects with height phobia (a specific phobia) has also demonstrated that DCS facilitates the effects of ERP therapy. Current theories postulate that DCS facilitates fear extinction by enhancing the learning process and increasing consolidation of memories, but the neural mechanisms underlying this process are not understood. The proposed research aims to elucidate these mechanisms by using fMRI to measure brain activation during 1) symptom provocation and verbal learning two hours post-medication, and 2)repeated symptom provocation and verbal recognition one week post-medication. This research will also examine the effects of DCS on cognitive functioning using neuropsychological testing both two house and one week post-medication.
Investigators
Cary Savage, Ph.D.
Director, CHBN and John H. Wineinger Professor of Psychiatry and Behavioral Sciences
University of Kansas
Eligibility Criteria
Inclusion Criteria
- •Right-handed
- •Adults between 18 and 55 years of age
- •Subjects in the phobic group will additionally meet diagnostic (DSM-IV) criteria for spider phobia.
- •Individuals of both genders and all races will be included
Exclusion Criteria
- •Women who are breastfeeding or pregnant
- •Individuals with medical conditions unsuitable for MR scanning
- •Individuals reporting a history of epilepsy or seizures
- •Individuals reporting an allergy to cycloserine
- •Individuals diagnosed with asthma or who report previous anaphylactic reaction to insect stings/bites, medication, food, or other material and/or event
- •Individuals reporting present or past diagnosis of a developmental disorder, neurological disorder, or head injury \*Individuals found to have Axis I psychopathology as defined by the DSM-IV (other than spider phobia)
- •Individuals currently taking any psychotropic medication
Arms & Interventions
Non-Phobic Control - Placebo
Participants without phobia will be given one placebo administration.
Intervention: Placebo
Non-Phobic Control - DCS
Participants without phobia will be given one D-cycloserine (DCS) administration of 100mg.
Intervention: D-cycloserine
Spider-phobic Placebo
Participants with phobia will be given one placebo administration.
Intervention: Placebo
Spider-phobic DCS
Participants with phobia will be given one D-cycloserine (DCS) administration of 100mg.
Intervention: D-cycloserine
Outcomes
Primary Outcomes
fMRI Brain Activations During Symptom Provocation
Time Frame: 2 Weeks
Regions of interest (ROIs) were specified based on previous research and included amygdala, insula, dorsal anterior cingulate cortex (ACC), dorsolateral PFC (dlPFC), and hippocampus. Multiple regression analyses were used to examine differences in response between experimental conditions (spider versus butterfly images). For significant clusters of activation within ROIs, the average max percent signal change is reported. For other regions, the average max percent signal change is reported within a sphere centered at coordinates identified via previous research.
Secondary Outcomes
- Cognitive Functioning Measured Using the Iowa Gambling Test(2 weeks)
- Cognitive Functioning Measured Using the Wisconsin Card Sorting Task(2 weeks)
- Cognitive Functioning Measured Using the Wechsler Memory Scale III (Logical Memory and Faces Subtests)(2 Weeks)
- Cognitive Functioning Measured Using the Rey-Osterrieth Complex Figure Test (RCFT)(2 weeks)