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Evidence for a Central Fear Mechanism

Jack M. Gorman, MD; Justine Kent, MD; Jose Martinez, MA; Susan Browne, BA; Jeremy Coplan, MD; Laszlo A. Papp, MD

Arch Gen Psychiatry. 2001;58:125-131.

Background  Inhalation of carbon dioxide (CO₂) 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) may 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.

From the Department of Psychiatry, Columbia University, and Biological Studies Unit, New York State Psychiatric Institute, New York, NY.

Corresponding author and reprints: Jack M. Gorman, MD, Department of Psychiatry, Columbia University, 1051 Riverside Dr, Unit 32, New York, NY 10032.

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