We propose to investigate the pathoDhvsiology of three anxiety disorders: posttraumatic stress disorder (PTSD) panic disorder (PD). and specific phobia (SP). We will use cognitive activation paradigms and magnetic resonance imaging (MRI) to probe the function and structure of implicated amygdalo-cortical circuitry. Convergent data implicate 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 pregenual anterior cingulate cortex, subcallosal cortex, and hippocampus. Though convergent data from neuroimaging studies support this model, we propose to extend this line of research in several respects: 1) use an approach that enables the characterization of habituation/sensitization of amygdala response, to investigate this temporal dimension. Preliminary data suggest that both PTSD and PD may be characterized by sensitization (vs. habituation) of amygdala responses to threat-related stimuli. 2) measure perigenual cortical and amygdala function in the same subjects, to enable a quantitative assessment of the relationship between these brain regions. Such a systems level approach is necessary if pathophysiology or correlates of clinical indices are related to inter-regional interactions. 3) investigate the relationship between abnormal brain structure and abnormal function; we plan to use modern cortical parcellation methods and a new technique for measuring cortical thickness. The cortical thickness method will enable us to: A) decompose volumetric differences to determine the relative contributions of cortical thickness and cortical surface area, and B) map the topographic concordance between observed functional and structural differences. 4) study psychiatric comparison groups, in addition to normal comparison and trauma-exposed normal comparison subjects, in order to determine the specificity (vs. generalizability) of findings among these anxiety disorders.
