This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The etiology of panic disorder remains unknown. Yet a convergence of data from neuroscience research on fear and clinical research on anxiety suggests panic disorder may be explained by a combination of genetically determined hypersensitivity of the brains fear pathways and the influence of stressful life events. There is also abundant evidence from both animal and human studies that stressful life events can impact on functioning of the brain's fear pathways and are associated with development, onset, and relapse of panic disorder. We have previously demonstrated significant abnormalities in cardiovascular and respiratory function measures in individuals with panic disorder. The control of the heart and lungs is affected by regions of the brain involved in the response to stress and the development of anxiety. We now plan to investigate the relationships of stressful life events, the brain's control of cardiovascular and respiratory function, and the potential for relapse after successful treatment of panic disorder. Using non-invasive methods, we will obtain measures of cardiovascular and respiratory function in panic disorder patients along with a rigorous historical assessment of stressful life events. We will then use a combination of cognitive behavioral therapy and the antidepressant sertraline, both with well-validated efficacy for the treatment of panic disorder, and obtain repeated stress, cardiovascular, and respiratory measures during and after such treatment. The acute treatment phase is 3 months, the maintenance treatment phase is another 3 months, and the follow-up, no-treatment phase is 12 months. This investigation will enable us to test whether patients with panic disorder are vulnerable to the impact of stressful life events and what are the relationships with cardiovascular and respiratory function and panic relapse before, during, and after treatment. These relationships may offer important data for directing treatment approaches and allowing clinicians to test for vulnerability to panic disorder.
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