Aberrant respiratory sensitivity to CO2 as a trait of familial panic disorder

Background: According to three earlier studies, well individuals with a family history of panic disorder experience more anxiety following a single breath of 35% CO2 than do those without such a family history. This study sought to determine whether a heightened sensitivity to CO2 manifests specifically in respiratory changes. Methods: Subjects were 18-35 years old and had no history of panic attacks and no current DSM-IV diagnosis other than simple or social phobia. Those at high risk for panic disorder (HR-P) (n = 46) had a first-degree relative with treated panic disorder. Low-risk control subjects (LR-C) (n = 39) had no first-degree relative with panic disorder. Respiratory measurements were taken continuously while subjects breathed room air through an attached mask for 3 min and, subsequently, while they breathed a 5% CO2/air mixture for an additional 3 min. Results: HR-P subjects did not differ from control subjects by group means of the principal measure of respiratory response, changes in minute volume (MV) during CO2 inhalation. However, these values assumed clearly different distributions in the two groups. Fifteen (32.6%) of the HR-P subjects showed a paradoxical decrease in MV while breathing CO2 and six (13%) displayed a particularly rapid increase in MV. Only slope and none had a high value [chi (2)(1) = 12.3, p < .001, p = .021, Fisher exact test, respectively]. Though the subjects with high MV increases also described greater increases in anxiety after breathing CO2, a regression analysis indicated that the MV increase was the more important in discriminating high-risk from control subjects. Conclusions: These results suggest that respiratory sensitivity to CO2 inhalation is operative in the familial transmission of panic disorder. Biol Psychiatry 2001;49:582-587 (C) 2001 Society of Biological Psychiatry.