Anxiety responses to CO2 inhalation in subjects at high-risk for panic disorder

Background: A number of reports have shown that patients with panic disorder have greater anxiety responses to the inhalation of enhanced carbon dioxide mixtures than do well controls or patients with other psychiatric illnesses. Three earlier studies have shown that well individuals who have first-degree relatives with panic disorder also experience more anxiety following CO2 than do controls without such a family history. The following was undertaken to confirm and extend these findings. Methods: Well subjects at high risk for panic disorder (HR-P, n = 132) had a first-degree family member with treated panic disorder but no personal history of panic attacks. Low-risk subjects (LR-C, n = 85) had no such family history. All underwent a diagnostic interview with the SADS-LA and completed a battery of self-rating scales before undergoing two CO2 challenges. One involved a single vital capacity breath of air and then of 35% CO2 and the other 5 min of air and then 5 min of 5% CO2. Results: In comparison to the LR-C group, HR-P subjects had higher scores on various self-ratings of anxiety and depression and were more likely to have a lifetime diagnosis of MDD or of an anxiety disorder. NEO neuroticism and a history of MDD were the most important of these measures in separating the high-risk and low-risk groups. As predicted, the HR-P subjects experienced more anxiety following 35% CO2 exposure. The removal of individuals with lifetime diagnosis of MDD or of an anxiety disorder eliminated the relationship of neuroticism to CO2-induced anxiety and strengthened the relationship between the CO2 response and a family history of panic disorder. Five minutes of 5% CO2 produced much lower increases in anxiety than did the 35% exposure, but a dose by group interaction suggested that increasing exposure increased anxiety preferentially in the high-risk subjects. Conclusion: The results confirm earlier findings in indicating that a family history of panic disorder conveys a liability to experience anxiety with CO2 exposure. They also suggest that this anxiety may reflect several discrete diatheses of relevance to the heritability of panic disorder. (c) 2005 Elsevier B.V All rights reserved.