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Daniel S. Pine, MD; Rachel G. Klein, PhD; Jeremy D. Coplan, MD; Laszlo A. Papp, MD; Christina W. Hoven, DrPH; Jose Martinez, MS; Pavel Kovalenko, PhD; Donald J. Mandell; Donna Moreau, MD; Donald F. Klein, MD; Jack M. Gorman, MD

Arch Gen Psychiatry. 2000;57:960-967.

Background  To examine the relationship between respiratory regulation and childhood anxiety disorders, this study considered the relationship between anxiety disorders and symptoms during carbon dioxide (CO₂) exposure, CO₂ sensitivity in specific childhood anxiety disorders, and the relationship between symptomatic and physiological responses to CO₂.

Methods  Following procedures established in adults, 104 children (aged 9-17 years), including 25 from a previous study, underwent 5% CO₂ inhalation. The sample included 57 probands with an anxiety disorder (social phobia, generalized anxiety disorder, separation anxiety disorder, and panic disorder) and 47 nonill comparison subjects. Symptoms of anxiety were assessed before, during, and after CO₂ inhalation.

Results  All children tolerated the procedure well, experiencing transient or no increases in anxiety symptoms. Children with an anxiety disorder, particularly separation anxiety disorder, exhibited greater changes in somatic symptoms during inhalation of CO₂-enriched air, relative to the comparison group. During CO₂ inhalation, symptom ratings were positively correlated with respiratory rate increases, as well as with levels of tidal volume, minute ventilation, end-tidal CO₂, and irregularity in respiratory rate during room-air breathing.

Conclusions  Childhood anxiety disorders, particularly separation anxiety disorder, are associated with CO₂ hypersensitivity, as defined by symptom reports. Carbon dioxide hypersensitivity is associated with physiological changes similar to those found in panic disorder. These and other data suggest that certain childhood anxiety disorders may share pathophysiological features with adult panic disorder.

From the New York State Psychiatric Institute and Columbia University, New York (Drs Pine, Coplan, Papp, Hoven, Kovalenko, Moreau, D. F. Klein, and Gorman and Messrs Martinez and Mandell); and New York University Child Study Center, New York (Dr R. G. Klein).

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