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

J Affect Disord. 2006 May;92(1):63-70. doi: 10.1016/j.jad.2005.12.045. Epub 2006 Mar 9.


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 CO(2) 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 CO(2) challenges. One involved a single vital capacity breath of air and then of 35% CO(2) and the other 5 min of air and then 5 min of 5% CO(2).

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% CO(2) exposure. The removal of individuals with lifetime diagnosis of MDD or of an anxiety disorder eliminated the relationship of neuroticism to CO(2)-induced anxiety and strengthened the relationship between the CO(2) response and a family history of panic disorder. Five minutes of 5% CO(2) 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 CO(2) exposure. They also suggest that this anxiety may reflect several discrete diatheses of relevance to the heritability of panic disorder.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Anxiety Disorders / diagnosis*
  • Anxiety Disorders / epidemiology*
  • Carbon Dioxide / administration & dosage
  • Carbon Dioxide / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Panic Disorder / diagnosis*
  • Panic Disorder / epidemiology*
  • Panic Disorder / genetics
  • Risk Factors
  • Severity of Illness Index


  • Carbon Dioxide