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

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.

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