Study of Brain Circuitry in Anxiety Disorders

Probing Amygdalo-Cortical Circuitry in Anxiety Disorders

A diverse body of research has implicated the amygdalo-cortical circuitry in the pathophysiology of anxiety disorders. For example, one model of PTSD posits exaggerated amygdala responsivity to threat-related stimuli as well as deficient top-down modulation of amygdala responses by specific cortical regions, including the pregenual anterior cingulate cortex, subcallosal cortex, and hippocampus.

The investigators propose to investigate the pathophysiology of several specific anxiety disorders, Posttraumatic Stress Disorder (PTSD), Panic Disorder (PD), and Specific Phobia(SP), by using cognitive activation paradigms and magnetic resonance imaging (MRI) to probe the function and structure of implicated amygdalo-cortical circuitry.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder; Panic Disorder; Specific Phobias

Detailed Description

All candidates for this project will undergo a comprehensive clinical assessment by an investigator trained to administer these instruments. At the MGH fMRI Center in Charlestown or at the Neuroimaging Center at McLean Hospital in Belmont, MA; each subject will undergo a single MRI session lasting approximately 2 hours. After the scanning session, subjects may be asked to make judgments about the facial expressions or the words that were presented.

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Boston metropolitan area

Description

Inclusion Criteria:

• 18 - 65 years of age
• Right-handed (Edinburgh Inventory - Oldfield 1971)
• SCID diagnosis consistent with group designation:

Current PTSD (PTSD group; none current or past (NC and TENC group); Current SP (must be to small animal phobia, SP group); Current PD (PD group)

• To be matched for age, gender, and years of education, as well as self-identified race/ethnicity.
• For female subjects, stage of menstrual cycle will be ascertained by history (see appendix), and dates of fMRI acquisition will be scheduled to prevent systematic differences between groups with respect to this variable.

Exclusion Criteria:

• Neurologic or medical condition that would interfere with study procedures or confound results, ascertained by history.
• History of seizure or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion)
• History of exclusionary Axis I psychiatric diagnosis (other than as specified); i.e., history of substance use disorder, psychotic disorder, bipolar disorder, tic disorder, or eating disorder. Note that comorbid current major depressive disorder will be allowed in up to one half of each study group. This will enable inclusion of this common comorbidity, but also enable a definitive assessment of whether or not the presence of this comorbid diagnosis is driving any observed significant between group differences.
• Use of psychotropic medication within 4 weeks prior to study (within 6 weeks for fluoxetine, or other long-lived compounds; within one year for neuroleptics).
• Pregnancy (to be ruled out by urine ß-HCG).
• Metallic implants or devices contraindicating magnetic resonance imaging.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Control; Healthy Controls
Posttraumatic Stress Disorder; Participants with Posttraumatic Stress Disorder
Panic Disorder; Participants with Panic Disorder
Specific Phobia; Participants who have specific phobias

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
amygdala activation during Masked Affect Task	measured once at fMRI session

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Scott L Rauch, MD, McLean Hospital

Publications and helpful links

General Publications

• Rosso IM, Makris N, Britton JC, Price LM, Gold AL, Zai D, Bruyere J, Deckersbach T, Killgore WD, Rauch SL. Anxiety sensitivity correlates with two indices of right anterior insula structure in specific animal phobia. Depress Anxiety. 2010 Dec;27(12):1104-10. doi: 10.1002/da.20765.
• Killgore WD, Britton JC, Price LM, Gold AL, Deckersbach T, Rauch SL. Neural correlates of anxiety sensitivity during masked presentation of affective faces. Depress Anxiety. 2011 Mar;28(3):243-9. doi: 10.1002/da.20788. Epub 2011 Feb 9.
• Britton JC, Gold AL, Deckersbach T, Rauch SL. Functional MRI study of specific animal phobia using an event-related emotional counting stroop paradigm. Depress Anxiety. 2009;26(9):796-805. doi: 10.1002/da.20569.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: April 26, 2013
• First Submitted That Met QC Criteria: May 7, 2013
• First Posted (Estimate): May 8, 2013

Study Record Updates

• Last Update Posted (Estimate): May 8, 2013
• Last Update Submitted That Met QC Criteria: May 7, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Disease; Anxiety Disorders; Stress Disorders, Post-Traumatic; Panic Disorder
• Other Study ID Numbers: 1R01MH070730-01A2 (U.S. NIH Grant/Contract)