Generalized Anxiety Disorder and Social Anxiety Disorder: Their Impact on the Processing of Information and Learning

There have been suggestions that the threshold for amygdala activity is lower in individuals
with anxiety disorders than in healthy individuals. However, despite it's immediate
plausibility, there have been relatively few tests of this hypothesis. Specifically, there
have been very few explorations of the performance of patients with anxiety disorders on
measures known to implicate the amygdala.

Although the high co-morbidity of Generalized Anxiety Disorder (GAD) and Social Anxiety
Disorder (SAD) complicates the issue, the fact that the disorders doubly dissociate suggests
that they are due to dysfunctional activity in separable neurocognitive systems. We would
suggest that the hyper-responsive amygdala hypothesis is more likely to be linked to the
explanation of GAD. In contrast, SAD may be due to reduced activation thresholds for units in
a system that responds to social threat and which recruits lateral orbital frontal cortex.
Thus, the current project will determine the performance of patients with GAD and SAD on
measures in which the amygdala is known to play a role and also measures that recruit lateral
orbital frontal cortex and the system for social response reversal. In addition, two proposed
neuro-imaging studies will directly assess neural responses in these two systems in both
patient populations. The project should provide clear data that will constrain future
theorizing on the pathology implicated in these two disorders.

- INCLUSION CRITERIA:

Age: Participants will be males and females, 18-50 years of age.

IQ: IQ, as measured by 4 subscales from the Wechsler Adult Intelligence Scale-Revised
(WAIS-R), must be > 80.

Medication status: No regular use of psychotropic medication within 2 weeks of the study
(or fluoxetine within 8 weeks of the study). No regular use of any benzodiazepine. We
intend to identify patients whose GAD/SAD is currently untreated.

EXCLUSION CRITERIA:

Because factors such as psychiatric disease, or CNS disease, can influence functional brain
activity, and pregnancy precludes participation in fMRI studies, these factors are
exclusionary.

1. Psychiatric history: Participants will be assessed using DSM-IV criteria via
standardized psychiatric interviews conducted by trained examiners (i.e., SCID). Any
current suicidal ideation will be exclusionary.

1. Healthy comparison individuals (Group 1): All participants will be free of any
current psychiatric disorder as well as lifetime history of psychosis, pervasive
developmental disorder, major affective disorder, panic disorder, obsessive
compulsive disorder, conduct disorder, ADHD, anorexia.

2. Patients with GAD (Group 2): Any history of an axis I diagnosis excluding SAD but
not including adjustment disorder, simple phobia or dysthymia is exclusionary.
There must be no current mood disoder (MD) though patients with past MD, which
occurred after the onset of GAD, will be admitted to the study. We recognize the
difficulty of recruiting patients with GAD without co-morbid SAD and will
therefore allow patients who are comorbid into the study in this group. We have
faced difficulties with our studies of children with psychopathic tendencies
where, although it is possible to identify populations who only meet criteria for
ADHD most children who meet criteria for psychopathic tendencies are co-morbid
for ADHD. We will adopt a similar strategy to our work with children; i.e., in
contrasts of patients with GAD with comparison individuals, we will use SAD
symptomatology as a covariate to reduce, and evaluate, the impact of pathology
associated with SAD on the data.

3. Patients with SAD (Group 3): Any current history of an axis I diagnosis including
GAD, but excluding adjustment disorder, simple phobia or dysthymia is
exclusionary. There must be no current mood disorder (MD) though patients with
past MD, which occurred after the onset of SAD, will be admitted to the study.

2. History of Drug Abuse: Axis I diagnoses of substance use disorders will be
exclusionary.

3. Severe acute and chronic medical illnesses.

4. CNS disease: History of brain abnormalities (e.g., neoplasms, subarachnoid cysts),
cerebrovascular disease, infectious disease (e.g., abscess), or other neurological
disease, or history of head trauma (defined as loss of consciousness > 3 min).

5. Metal or electronic objects: Metal plates, certain types of dental braces, cardiac
pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI
scans.

6. Claustrophobia: Participants will be questioned about potential discomfort in being in
an enclosed space, such as an MRI scanner.

7. Pregnancy status: Because of the potential effects of hormonal changes on brain
function as well as the unknown effects of electromagnetic field on the fetus, known
pregnancy is an exclusion criterion.