A new field of anxiety disorder inquiry has been stimulated by the relatively recent """"""""re-discovery"""""""" that carbon dioxide inhalation provokes panic attacks and heightened anxiety in patients suffering from panic disorder. The goals of this proposal are to specifically test the hypothesis that patients with panic disorder are hypersensitive to carbon dioxide and determine the proportion of patients who will experience acute panic during inhalation of 3%, 5%, 7% carbon dioxide. In addition, we wish to study the biological and characterological aspects of patients who are sensitive to CO2, as well as the physiological concomitants of an acute carbon dioxide-induced panic attack. A major aim of this research will be to determine if patients previously shown to be sensitive to CO2 are still vulnerable to CO2 once their spontaneous panic attacks have been blocked by anti-panic medications. Finally, we will also study the effect of room air hyperventilation on patients with panic disorder as a comparison to CO2 challenge. This proposal extends our previous work in several ways including a much larger sample size, use of diagnostic and intervention blind to rate the occurrence of panic attacks, more fine-grained biochemical assessments during the experiment, and construction of CO2 response curves. The study will be conducted on a total of 100 patients with panic disorder and 50 normal volunteers. Each subject will undergo a respiratory challenge procedure in which they are administered varying concentrations of CO2 and also asked to hyperventilate room air to induce alkalosis. During the procedure, arterial blood gas and pH determination are made and blood is also collected for a variety of other measures. Breath by breath spirometry is provided by an on-line computer and a continuous heart rate recording is made. Patients will then be treated with anti-panic medication and, when panic-free for one month, restudied in the respiratory challenge procedure. Our working hypothesis is that patients with panic disorder have abnormal sensitivity to CO2 which leads them to chronically hyperventilate in order to maintain low arterial Pco2. The medullary chemoreceptors and/or locus ceruleus may mediate this CO2 hypersensitivity. Anti-panic drugs raise the threshold to CO2 response and should block CO2 panic attacks and anxiety.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH041778-03
Application #
3380564
Study Section
(PCBB)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
3
Fiscal Year
1988
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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