Carbon dioxide induces erratic respiratory responses in bipolar disorder

Background: CO₂ respiration stimulates both anxiety and dyspnea ("air hunger") and has long been used to study panic vulnerability and respiratory control. High comorbidity with panic attacks suggests individuals with bipolar disorder may also mount a heightened anxiety response to CO₂. Moreover, problems in the arousal and modulation of appetites are central to the clinical syndromes of mania and depression; hence CO₂ may arouse an abnormal respiratory response to "air hunger". Methods: 72 individuals (34 bipolar I, 25 depressive and bipolar spectrum, 13 with no major affective diagnosis) breathed air and air with 5% CO₂ via facemask for up to 15 min each; subjective and respiratory responses were recorded. Results: Nearly half the subjects diverged from the typical response to a fixed, mildly hypercapneic environment, which is to increase breathing acutely, and then maintain a hyperpneic plateau. The best predictors of an abnormal pattern were bipolar diagnosis and anxiety from air alone. 25 individuals had a panic response; panic responses from CO₂ were more likely in subjects with bipolar I compared to other subjects, however the best predictors of a panic response overall were anxiety from air alone and prior history of panic attacks. Limitations: Heterogeneous sample, liberal definition of panic attack. Conclusion: Carbon dioxide produces abnormal respiratory and heightened anxiety responses among individuals with bipolar and depressive disorders. These may be due to deficits in emotional conditioning related to fear and appetite. Although preliminary, this work suggests a potentially useful test of a specific functional deficit in bipolar disorder.