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Onset of Spontaneous Panic Attacks: A Prospective Study of Risk Factors

From the University of Iowa Carver College of Medicine, Iowa City, Iowa (W.C., L.D.); Columbia University School of Medicine, New York, New York (A.F.); National Institute of Mental Health, Bethesda, Maryland (D.S.P.).

Address correspondence and reprint requests to William Coryell, MD, University of Iowa Carver College of Medicine, Department of Psychiatry, 2–205 MEB, Iowa City, IA 52242. E-mail: william-coryell{at}uiowa.edu.

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.

Key Words: panic disorder • carbon dioxide • trait marker • follow-up • neuroticism

Abbreviations: VAS-A = visual analogue scale–anxiety; DSM-III-R = Diagnostic and Statistical Manual III–Revised; MV = minute volume; NEO-PI = NEO Personality Inventory; HR = hazard ratio.

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