Physiological changes during carbon dioxide inhalation in patients with panic disorder, major depression, and premenstrual dysphoric disorder - Evidence for a central fear mechanism

Background: Inhalation of carbon dioxide (CO,) has been shown to produce more anxiety in patients with panic disorder (PD) than in healthy comparison subjects or patients with most other psychiatric illnesses tested, although premenstrual dysphoric disorder (PMDD) ma?; be an exception. Several reasons have been proposed to explain CO2 breathing effects in PD. We examined differences in respiratory response to CO2 breathing in 4 groups to address these issues. Methods: Patients with PD (n=52), healthy controls (n=32), patients with PMDD (n=10), and patients with major depression without panic (n=21) were asked to breathe 5% and 7% CO2. Continuous measures of respiratory physiological indices were made. Results: Carbon dioxide breathing produced the expected increases in all 4 respiratory variables measured. More patients with PD and PMDD had panic attacks than did controls or patients with major depression. Subjects who experienced panic during 5% or 7% CO2 inhalation had the most extreme increases regardless of diagnostic group. Among patients with PD, baseline end-tidal carbon dioxide levels were significantly lower in those who subsequently had a panic attack during 5% CO2 breathing than those who did not. Conclusions: Although CO2 breathing causes a higher rate of panic attacks in patients with PD than other groups (except PMDD), the physiological features of a panic attack appear similar across groups. Once a panic attack is triggered, minute ventilation and respiratory rate increase regardless of whether the subject carries a PD diagnosis. These findings are compatible with preclinical fear conditioning models of anxiogenesis.