AUTONOMIC CARDIOVASCULAR CONTROL IN ANXIETY AND STRESS

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In this revised application for an ADAMHA Scientist Development Award (Level I), a program of supervised training and research is proposed to study autonomic nervous system (ANS) control of cardiovascular function in anxiety and psychological stress. The overall objective is to learn how the brain controls the cardiovascular system during psychological stress. Dr. Jack Gorman will be the preceptor of the program. The candidate will receive instruction in HR, BP, and respiration signal processing, analysis, and model building from Drs. Richard Cohen and J. Thomas Bigger and apply these approaches in several experiments conducted under their supervision. In addition, the candidate will take courses in neuroscience, neuroanatomy, and engineering conduct and two other studies, under the supervision of Dr. Harold Sackeim, to evaluate descending cortical influences on ANS control mechanisms of HR, BP, and respiration. ANS control underlies the normal cardiovascular response to psychological stress, and dysregulation of the control is widely hypothesized to play a role in the pathophysiology of various psychiatric and cardiovascular disorders. For example, exaggerated hemodynamic responsiveness to challenging events is thought to characterize normal individuals at risk for coronary heart disease (CHD) [1] as well as patients with panic disorder (PD) [2,3]. Despite evidence suggesting disordered ANS regulation of cardiovascular function in these conditions, the origins of the exaggerated responses are not well understood. Recently, several noninvasive approaches to assessment of ANS cardiovascular control have been developed for application to human studies. One such approach employs analysis of beat-to-beat variability of biological signals, primarily heart rate (HR) [4=-7], to model the cardiovascular control system. This approach has had wide application in medicine [8, 01], neonatology [10, 11], gerontology [12, 13], and cardiology [14, 18] and more recent introduction in psychiatry [19, 20]. Other informative approaches have utilized clinically derived "natural experiments" of ECT, unilateral cerebral inactivation, stroke, and cardiac transplantation to study descending influences on CV regulation. Accordingly, in this application, the candidate proposes to use new signal processing approaches to investigate ANS control of CV function under psychological stress in normal subjects in the laboratory under various conditions and at the worksite. Additional studies of patients undergoing the Wada procedure and ECT will asses CV regulation under conditions in which descending control of CV regulation is disrupted. These studies will be supplemented with coursework in neuroscience. Together, these approaches will be useful in elucidating the mechanisms underlying hemodynamic responses to anxiety and psychological stress. Thus, the overall objective of this proposal is to study autonomic control of heart rate, blood pressure, and respiratory responses toward an understanding of the hemodynamic effects underlying the anxious response. Understanding the mechanisms of these effects may lead to advances in treatment and prophylaxis.