Persistent respiratory irregularity in patients with panic disorder

Background: Dysregulated respiratory control may play a role in the pathoph ysiology of panic disorder. This could be due to abnormalities in brain ste m respiratory nuclei or to dysregulation at higher brain levels. Results fr om previous studies using the doxapram model of panic have yielded an uncle ar picture. A brief cognitive manipulation reduced doxapram-induced hyperve ntilation in patients, suggesting that higher level inputs can substantiall y alter their respiratory patterns. However, respiratory abnormalities pers isted, including a striking irregularity in breathing patterns. Methods: To directly study respiratory irregularity, breath-by-breath recor ds of tidal volume (V-t) and frequency (f) from previously studied subjects were obtained. Irregularity was quantified using von Neumann's statistic a nd calculation of "sigh" frequency in 16 patients and 16 matched control su bjects. Half of each group received a standard introduction to the study an d half received a cognitive intervention designed to reduce anxiety/distres s responses to the doxapram injection. Results: Patients had significantly greater V-t irregularity relative to co ntrol subjects. Neither the cognitive intervention nor doxapram-induced hyp erventilation produced significant changes in V-t irregularity. The V-t irr egularity was attributable to a sighing pattern of breathing that was chara cteristic of panic patients but not control subjects. Patients also had som ewhat elevated f irregularity relative to control subjects. Conclusions: The irregular breathing patterns in panic patients appear to b e intrinsic and stable, uninfluenced by induced hyperventilation or cogniti ve manipulation. Further study of V-t irregularity and sighs are warranted in efforts to localize dysregulated neural circuits in panic to brain stem or midbrain levels. Biol Psychiatry 2001;49:588-595 (C) 2001 Society of Bio logy Psychiatry.