This five-year career development proposal will establish Dr. Seth D. Fdedman as an independent researcher who can develop, apply, and integrate rapid high-field multinuclear magnetic resonance spectroscopy (MRS) and peripheral physiological monitoring to study biological regulation in anxiety disorders. Towards this aim, a detailed curriculum of physics, digital signal processing, physiology, and statistical methods will be undertaken. Regular training visits to centers with critical expertise are also planned to facilitate technical and clinical skill development. The studies associated with this training experience will be conducted in three phases: (1) technical development and characterization of hyperventilation (HV) response in healthy control subjects, (2) clinical investigation of HV dysregulation in panic disorder subjects compared to healthy controls and social phobia subjects, and (3) pilot work focused on alternative challenges. In PD, a number of peripheral alterations are found at rest (increased sighing, low pCO2, and respiratory variability) and in response to HV, with delayed recovery of end-tidal pCO2 commonly demonstrated. Importantly, anxiety level per se is not sufficient to produce this delayed recovery, since SP subjects, who will be used as anxious controls in the proposed studies, do not demonstrated altered pCO2 recovery following HV. Central nervous system alterations of lactate production are also demonstrated in response to HV challenge in PD, a response suggested to be in excess of the observed metabolic alkalosis. By integrating time-resolved central and peripheral nervous system measures of physiological regulation, the components of altered physiology in PD will be elucidated.
|Saneto, Russell P; Friedman, Seth D; Shaw, Dennis W W (2008) Neuroimaging of mitochondrial disease. Mitochondrion 8:396-413|
|Friedman, Seth D (2008) Taking responsibility for scientific discourse. Science 321:1039-40|
|Friedman, Seth D (2008) Comment on ""Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain"". Science 321:640;author reply 640|
|Friedman, Seth D; Jensen, J Eric; Frederick, Blaise B et al. (2007) Brain changes to hypocapnia using rapidly interleaved phosphorus-proton magnetic resonance spectroscopy at 4 T. J Cereb Blood Flow Metab 27:646-53|
|Friedman, Seth D; Mathis, C Mark; Hayes, Cecil et al. (2006) Brain pH response to hyperventilation in panic disorder: preliminary evidence for altered acid-base regulation. Am J Psychiatry 163:710-5|