Sensitivity to carbon dioxide and translational studies of anxiety disorders.

Heightened concentrations of CO2 in inhaled air provoke temporary acidification of the brain, followed by compensatory hyperventilation and increased arousal/anxiety. These responses are likely to map a basic, latent general alarm/avoidance system that is largely shared across mammals, and are sources of individual differences. By showing paroxysmal respiratory and emotional responses to CO2 challenges, humans with panic and separation anxiety disorders lie at one extreme of the distribution for CO2 sensitivity. This is also a developmental trait, sensitive to interference with parental cares. By sharing CO2 sensitivity with humans, rodents constitute a valuable resource to model panic and separation anxiety in the laboratory. Advantages of modeling CO2 sensitivity in rodents include non-inferential measurements (e.g. respiratory readouts) as proxies for human conditions, unbiased investigation of gene-environment interplays, and flexible availability of tissues for mechanistic studies. Data in humans and animals such as those reported in this issue of Neuroscience begin to reveal that CO2-driven behavioral responses stem from anatomo-physiological systems that are relatively separated from those subserving general dispositions to anxiety. This supports the notion that sensitivity to suffocative stimuli and ensuing human panic are significantly independent from trait/cognitive anxiety, and corroborates newer conceptualizations that distinguish between fear and anxiety circuitries.