Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity

Abstract

Background: Carbon 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 findings: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2) 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/significance: CO(2) 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 CO(2) may be part of a protective system triggered by suffocation and acute metabolic distress.

Figure 1. Peak scores on the Fear/Discomfort scale in four different CO₂ conditions.

a) eVAAS: air vs 9% p = 0.44; air vs 17.5% and vs 35% p ≤ 0.001; 9% vs 17.5% and vs 35% p ≤ 0.0001; 17.5% vs 35% p≤0.0001. b) Younger versus older subjects: p<0.05

Figure 2. Area Under the Curve on the Fear/Discomfort scale in four different CO₂ conditions.

a) eVAAS AUC score: air vs 9% p = 0.91; air vs 17.5% and vs 35% p ≤ 0.005; 9% vs 17.5% and vs 35% p ≤ 0.001; 17.5% vs 35% p≤0.0001. b) Time course of Fear/Discomfort in a single subject after the double inhalation of 0%, 9%, 17.5%, 35% CO₂ respectively.

Figure 3. Intensity of PSL panic symptoms in four different CO₂ conditions.

a) PSL: air vs 9% p = 0.76; air vs 17.5% and vs 35% p ≤ 0.0001; 9% vs 17.5% and vs 35% p ≤ 0.0001; 17.5% vs 35% p ≤ 0.0001. b) Younger versus older subjects: p = 0.217

Figure 4. DSM panic symptoms intensity in healthy subjects taking four different doses of CO₂.

Figure 5. Aggregate score of cognitive symptoms induced by four different CO₂ conditions in healthy subjects (“derealization-depersonalization” score+ “fear of loosing control-going crazy” score).