Panic attacks occur unexpectedly in panic disorder (PD), apparently independent from external events. Biological observations of natural panic attacks have been thwarted by the infrequency of such attacks, which often occur less than daily: capturing one when a patient is being physiologically monitored is difficult. Provocation of panic attacks in the laboratory by artificial means like lactate infusion (Liebowitz et al 1984, 1985) or carbon dioxide inhalation (Gorman et al 1994) is limited by the fact that it cannot be certain that induced attacks are identical with natural ones, either in physiologic characteristics or in mechanism. An alternative is to search for biological features that might underlie the susceptibility of patients with current panic disorder to attacks. Such features may be present more or less continuously, not just during attacks, being markers for PD as a “trait” rather than panic attacks as a “state.” In other psychiatric disorders, such features have been called “endophenotypical” (Lenzenweger 1999) because they are more hidden than phenotypic clinical symptoms.
A logical starting point is to look for fluctuations in biological features known to be associated with full-blown attacks but fluctuations of smaller magnitude, perhaps below the subject’s threshold for noticing them at all. Such features might reveal an instability that could on occasion escape its usual inhibitory mechanisms, analogous to the interictal electroencephalographic spikes present in certain epileptic patients. In PD, however, activity of autonomic nervous or cardiac systems is likely to be especially relevant. The cardiovascular system is a reasonable candidate because heart rate is a leading index of clinical anxiety in certain situations (Wilhelm and Roth 1998). The cardiac system is another because it has connections to panic through the suffocation false alarm hypothesis of Klein (1992) and observations of the hyperventilation syndrome (Ley 1985). Increased cardiac variability has been reported in PD at times when no clinical panic attacks were being provoked..................
