The DSM-IV classification of anxiety disorders postulates a number of distinct diseases presumed to have different biological underpinnings. Although physiological symptoms such as rapid heart beat and breathlessness are important component criteria for both Panic Disorder (PD) with and without agoraphobia, and Generalized Anxiety Disorder (GAD), diagnosis is based on subjective report of physiological disturbance rather than its objective measurement. The clinical phenomenology of PD and GAD suggests different temporal patterns, e.g., abrupt surges of activation in panic attacks versus more sustained activation in phobic situations and in GAD. While primarily characterized by sustained activation, GAD patients may also show short spikes of activation associated with intrusive, worried thoughts. Biologic mechanisms proposed to account for the phenomenology of PD, with and without agoraphobia, include autonomic instability, hyperventilation, suffocation false alarm, and epileptic discharge. Ambulatory monitoring and laboratory tests (relaxation, habituation, breath holding, hyperventilation, concomitants of thought, and classical conditioning) developed specifically to assess these physiological mechanisms will be used in two separate studies. Study 1 will compare 30 GAD patients, 30 PD patients with agoraphobia, and 30 controls. Study 2 will compare 20 PD patients with agoraphobia, 20 PD patients without agoraphobia, and 20 controls. In Study 2, ambulatory monitoring will include a behavioral avoidance test in a shopping mall. Analysis will determine if: 1. PD patients manifest more spontaneous autonomic fluctuations coinciding with dips and/or peaks in end-tidal pCO2 and electroencephalography changes suggesting epileptic discharge, than controls and GAD patients. 2. PD patients respond with more exaggerated psychophysiological reactions to dips and peaks in end-tidal pCO2 produced respiratory maneuvers than GAD patients or controls. 3. GAD patients and PD patients with agoraphobia habituate more slowly to noise bursts than PD patients without agoraphobia or controls. 4. Emotional conditioning to noise bursts is acquired more quickly and is more resistant to extinction in PD patients with agoraphobia than PD patients without agoraphobia or controls. 5. Physiological activation is related to subjective report of anxiety and panic and specific anxiety symptoms.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Medicine
United States
Zip Code
Blechert, Jens; Wilhelm, Frank H; Meuret, Alicia E et al. (2013) Experiential, autonomic, and respiratory correlates of CO2 reactivity in individuals with high and low anxiety sensitivity. Psychiatry Res 209:566-73
Ritz, Thomas; Rosenfield, David; Wilhelm, Frank H et al. (2012) Airway constriction in asthma during sustained emotional stimulation with films. Biol Psychol 91:8-16
Meuret, Alicia E; Rosenfield, David; Wilhelm, Frank H et al. (2011) Do unexpected panic attacks occur spontaneously? Biol Psychiatry 70:985-91
Blechert, Jens; Wilhelm, Frank H; Meuret, Alicia E et al. (2010) Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO? enriched air in panic disorder, social phobia, and healthy controls. Biol Psychol 84:104-11
Burkhardt, Susan C A; Wilhelm, Frank H; Meuret, Alicia E et al. (2010) Temporal stability and coherence of anxiety, dyspnea, and physiological variables in panic disorder. Biol Psychol 85:226-32
Ritz, Thomas; Wilhelm, Frank H; Meuret, Alicia E et al. (2009) Do blood phobia patients hyperventilate during exposure by breathing faster, deeper, or both? Depress Anxiety 26:E60-7
Meuret, Alicia E; Wilhelm, Frank H; Ritz, Thomas et al. (2008) Feedback of end-tidal pCO2 as a therapeutic approach for panic disorder. J Psychiatr Res 42:560-8
Wilhelm, Frank H; Pfaltz, Monique C; Grossman, Paul et al. (2006) Distinguishing emotional from physical activation in ambulatory psychophysiological monitoring. Biomed Sci Instrum 42:458-63
Alpers, Georg W; Wilhelm, Frank H; Roth, Walton T (2005) Psychophysiological assessment during exposure in driving phobic patients. J Abnorm Psychol 114:126-39
Roth, Walton T; Wilhelm, Frank H; Pettit, Dean (2005) Are current theories of panic falsifiable? Psychol Bull 131:171-92

Showing the most recent 10 out of 36 publications