Neural Functioning Underlying Anxiety and Its Treatment (The INSULA Study)

Neural Substrates of Anticipation and Interoception in Anxiety Disorders

This study will examine the effects of cognitive behavioral therapy on brain function in people with anxiety disorders.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders; Generalized Anxiety Disorder; Panic Disorder
• Intervention / Treatment: Behavioral: Cognitive behavioral therapy for anxiety

Detailed Description

Anxiety disorders are characterized by excessive and irrational fears of common situations that impair normal functioning. Neuroimaging allows researchers to examine brain functioning as people are presented with tasks that provoke or model anxiety. Neuroimaging research suggests that anxiety is moderated by a neural circuit involving three parts of the brain: the amygdala, the insula, and the prefrontal cortex (PFC). Increased activation of the amygdala and insula is associated with high anxiety, although activation of the PFC is thought to reduce anxiety. Cognitive behavioral therapy (CBT) is the only type of psychotherapy with strong evidence for effectively treating panic disorder (PD) and generalized anxiety disorder (GAD), but it only works about half the time. This study will use neuroimaging to examine when and how CBT affects brain functioning in people with PD and GAD. The long-term goals of the research are to develop neuroimaging as a diagnostic tool, to use neuroimaging to predict treatment response, and to understand which changes in brain functioning are related to successful treatment.

Participation in this study will last approximately 3 months. Four groups of participants will be recruited: healthy controls and people with PD, GAD, or social phobia (SP). All participants will undergo functional magnetic resonance imaging (fMRI) scanning-a measure of brain functioning-at the first visit. During the fMRI scan, participants will be asked to perform computerized tasks that involve responding to images. This will be the only visit that the healthy controls and people with SP complete; their inclusion in the study establishes a comparison point for the brain scans of the other participants. People with PD and GAD will then be asked to complete 10 sessions of CBT over a 10- to 14-week period. After 3 months, these participants will again undergo fMRI scanning. At 3 and 6 months after the completion of CBT, these participants will be asked to complete follow-up questionnaires about their anxiety.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High school or higher education
• DSM-IV diagnosis of panic disorder (with ongoing symptoms), generalized anxiety disorder, or both

Exclusion Criteria:

• Lifetime diagnosis of psychotic disorder, organic mental disorder, or bipolar I disorder
• Substance dependence within the last 12 months or diagnosis of alcohol or substance abuse within the past month
• Use of psychotropic or anti-epileptic medications within the past 6 weeks
• Heavy caffeine use, defined as drinking more than 6 caffeinated beverages per day
• Current smoker
• Possibility of pregnancy
• History of claustrophobia or difficulty lying flat for long periods
• Ferrous metal in the body

Exclusion Criteria for Healthy Controls only:

• Lifetime diagnosis of major depressive disorder (MDD), bipolar I or II disorder, panic disorder (PD), agoraphobia without panic, generalized anxiety disorder (GAD), social phobia (SP), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), or an eating disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive behavioral therapy; Participants with panic disorder or generalized anxiety disorder (GAD) will receive a course of individual cognitive behavioral therapy targeted at their principal disorder.	Behavioral: Cognitive behavioral therapy for anxiety; 10 sessions delivered over the course of 14 weeks and aimed at reducing pathological behaviors and patterns of thought; Other Names: CBT; Behavior Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood oxygen level dependent (BOLD) response in amygdala, insula, and medial prefrontal cortex, as measured with functional magnetic resonance imaging (fMRI)	Measured at baseline and after 10 to 14 weeks of treatment

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Murray B. Stein, MD, MPH, University of California, San Diego

Publications and helpful links

Helpful Links

• Click here for more information on the UCSD Anxiety Disorders Research Program

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: July 27, 2009
• First Submitted That Met QC Criteria: July 27, 2009
• First Posted (Estimate): July 28, 2009

Study Record Updates

• Last Update Posted (Estimate): December 31, 2012
• Last Update Submitted That Met QC Criteria: December 27, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Treatment; Cognitive Behavioral Therapy; Brain Imaging; Psychotherapy; Functional Brain Imaging
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Anxiety Disorders; Panic Disorder
• Other Study ID Numbers: R01MH065413 (U.S. NIH Grant/Contract); DATR A2-AIA