Hypersensitivity to carbon dioxide as a disease-specific trait marker

There is now substantial evidence that an abnormal threshold for suffocation alarm underlies panic disorder. Because this disorder is highly familial, evidence of an abnormal suffocation threshold may be apparent in high-risk individuals before they develop clinical illness. To explore this possibility, we used a single inhalation of 35% CO2 vs. air to evaluate 11 subjects who had at least one first-degree relative with DSM-III-R panic disorder, 13 who had at least two relatives treated for mania or for depression (HR-AD), and 15 low-risk controls who had no family history of panic disorder, affective disorder, or alcoholism (LR-C). All were aged 18–34 and had no history of panics or of any Research Diagnostic Criteria disorder. Five (45.5%) of the subjects at high risk for panic disorder, but none of the LR-C subjects (p = .007), nor any of the HR-AD subjects (p = .011), developed a panic attack following inhalation of the CO2 mixture.