We are applying for continuation of funding for studies of respiratory function and carbon dioxide (CO2) response in patients with panic disorder. A large body of research and clinical experience now indicates that respiratory disturbance, including hyperventilation and exaggerated response to inhaled CO2, is directly involved in the pathophysiology of panic disorder. We have fit this into a theoretical model for panic that involves respiratory hyperactivity, serotonergic hypoactivity, and exaggerated noradrenergic function at the level of the human brainstem. The studies proposed in this application are aimed at the respiratory portion of this theoretical triangle. Interim analysis of data generated during the present funding period confirms our original hypotheses that panic patients have resting respiratory hyperactivity, do not panic to room air hyperventilation, and have both behavioral and biological hypersensitivity to inhaled CO2. We also found that the panic response to 7% CO2 robustly discriminates between panic disorder patients and controls, that changing """"""""instructional set"""""""" does not alter panic response to CO2, and that imipramine, but not cognitive/behavioral therapy, decreases CO2 sensitivity. Finally, we successfully developed an ambulatory respiratory monitor that measures both respiratory frequency and tidal volume. In the next funding period we propose to answer four specific questions: 1) does panic to 7% CO2 have diagnostic specificity for panic disorder? 2) do patients with panic disorder have respiratory abnormalities outside of the laboratory and are in vivo panic attacks characterized by acute change in respiratory pattern? 3) can we replicate and extend the preliminary finding that antipanic medication, but not antipanic psychotherapy, decreases CO2 sensitivity? and 4) are there other cognitive manipulations such as creating the illusion of control and basic reassurance that affect panic to CO2?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041778-08
Application #
2245268
Study Section
Treatment Assessment Review Committee (TA)
Project Start
1986-08-01
Project End
1998-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Gorman, Jack M; Martinez, Jose; Coplan, Jeremy D et al. (2004) The effect of successful treatment on the emotional and physiological response to carbon dioxide inhalation in patients with panic disorder. Biol Psychiatry 56:862-7
Coplan, Jeremy D; Moreau, Donna; Chaput, France et al. (2002) Salivary cortisol concentrations before and after carbon-dioxide inhalations in children. Biol Psychiatry 51:326-33
Martinez, J M; Kent, J M; Coplan, J D et al. (2001) Respiratory variability in panic disorder. Depress Anxiety 14:232-7
Gorman, J M; Kent, J; Martinez, J et al. (2001) Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder: evidence for a central fear mechanism. Arch Gen Psychiatry 58:125-31
Pine, D S; Klein, R G; Coplan, J D et al. (2000) Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group. Arch Gen Psychiatry 57:960-7
Galanter, C A; Wasserman, G; Sloan, R P et al. (1999) Changes in autonomic regulation with age: implications for psychopharmacologic treatments in children and adolescents. J Child Adolesc Psychopharmacol 9:257-65
Welkowitz, L A; Papp, L; Martinez, J et al. (1999) Instructional set and physiological response to CO2 inhalation. Am J Psychiatry 156:745-8
Pine, D S; Coplan, J D; Papp, L A et al. (1998) Ventilatory physiology of children and adolescents with anxiety disorders. Arch Gen Psychiatry 55:123-9
Papp, L A; Martinez, J M; Klein, D F et al. (1997) Respiratory psychophysiology of panic disorder: three respiratory challenges in 98 subjects. Am J Psychiatry 154:1557-65
Kent, J M; Coplan, J D; Martinez, J et al. (1996) Ventilatory effects of tryptophan depletion in panic disorder: a preliminary report. Psychiatry Res 64:83-90

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