Onset of spontaneous panic attacks: a prospective study of risk factors.

OBJECTIVE: Earlier analyses have shown that, among currently well individuals with no history of panic attacks, a family history of panic disorder is associated with a greater likelihood of panic symptoms after exposure to 35% CO2 and of ventilatory-response abnormalities during inhalation of 5% CO2. An association of those features with a subsequent onset of panic attacks would compose additional evidence that they are trait markers for panic disorder.
METHODS: Subjects who were free of current Axis I disorders other than simple or social phobia and who had a first-degree relative with panic disorder (high risk) and subjects who had no first-degree relatives with panic disorder or major depressive disorder (low-risk) underwent two challenge procedures. The first measured anxiety responses to a single breath of 35% CO2, and the second measured ventilatory responses to a 3-minute exposure to 5% CO2. After a mean interval of 4 years, 66 high-risk (48 female; mean age = 23.0 years) and 24 low-risk subjects (15 female; mean age = 23.1 years) were questioned by telephone about the occurrence of any spontaneous panic attack in the interval.
RESULTS: Sixteen (23.9%) of the high-risk and one (4.2%) of low-risk subjects had experienced at least one spontaneous panic attack; Cox regression analyses revealed a significant relationship between abnormal ventilatory responses to 5% CO2 and the later onset of panic attacks. Subjective responses to 35% CO2 were not predictive. Neuroticism scores were not associated with abnormal ventilatory responses to CO2 but were also predictive of later panic attacks.
CONCLUSIONS: High neuroticism scores and abnormal ventilatory responses to 5% CO2 appear to be additive trait markers for panic disorder.