BackgroundCarbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet.Methodology/Principal FindingsSixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001). This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05).Conclusions/SignificanceCO2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO2 may be part of a protective system triggered by suffocation and acute metabolic distress.

A number of evidences have established that panic and respiration are closely related. Clinical studies indicated that respiratory sensations constitute a discrete cluster of panic symptoms and play a major role in the pathophysiology of panic. The aim of the present study was to explore the phenomenology of an experimental model of panic in healthy volunteers based on the hypothesis that: (1) we can isolate discrete clusters of panic symptoms, (2) respiratory symptoms represent a distinct cluster of panic symptoms, and (3) respiratory symptoms are the best predictor of the subjective feeling of panic, as defined in the DSM IV criteria.Sixty-four healthy volunteers received a double inhalation of four mixtures containing 0, 9, 17.5 and 35% CO 2, respectively, in a double-blind, cross-over, random design. An electronic visual analog scale and the Panic Symptom List (PSL) were used to assess subjective 'fear/discomfort' and panic symptoms, respectively. Statistical analyses consisted of Spearman's correlations, a principal component factor analysis of the 13 PSL symptoms, and linear regressions analyses.The factor analysis extracted three clusters of panic symptoms: respiratory, cognitive, and neurovegetative (r 2 ¼ 0.65). Respiratory symptoms were highly related to subjective feeling of fear/discomfort specifically in the CO 2 -enriched condition. Moreover, the respiratory component was the most important predictor of the subjective feeling of 'fear/discomfort' (b ¼ 0.54).The discrete clusters of symptoms observed in this study were similar to those elicited in panic attacks naturally occurring in patients affected by panic disorder. Consistent with the idea that respiration plays a crucial role in the pathophysiology of panic, we found that respiratory symptoms were the best predictors the subjective state defined in the DSM IV criteria for panic.