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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH069848-04
Application #
7154038
Study Section
Brain Disorders and Clinical Neuroscience 5 (BDCN)
Program Officer
Wynne, Debra K
Project Start
2003-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$122,618
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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