A competing continuation of a Senior Scientist Award (formerly Research Scientist Award) is requested. The main focus is the study of the neurobiology and treatment of anxiety disorders, particularly panic. The candidate has held three successive five-year "K" award grants from NIMH. Four main areas of research are proposed: 1) studies of respiratory physiology in PD; 2) the relationships among respiratory, noradrenergic, and serotonergic function in PD; 3) developmental aspects of anxiety disorder including a preclinical model of anxiety, studies of anxious children, and development of a geriatric anxiety program; and 4) the role of CNS innervation in the cardiovascular response to acute and chronic stress. A hypothetical model is presented that will guide the candidate in studies attempting to elucidated biological aspects of PD and their relationship to cognitive and behavioral aspects. This includes placing respiratory abnormalities in panic in their proper perspective, testing relationships among several brain systems in the pathogenesis of panic, and studying the effects of early life traumatic stress on the biological and behavioral predisposition to anxiety disorder. Work on the "heart-brain" interaction includes studying heart transplant patients as a model of cardiac denervation in order to isolate the precise mechanisms by which the CNS controls cardiovascular function. In this proposed continuation period, particular attention will be placed on training in several neuroimaging techniques. Pilot single photon emission computerized tomography (SPECT) and positron emission tomography (PET) studies are described and plans for the use of functional magnetic resonance imaging to study carbon dioxide (C02) responsive zones of brain are also planned.