title: Onset of spontaneous panic attacks: a prospective study of risk factors.
abstract: 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.
authors.affiliation: University of Iowa Carver College of Medicine, Department of Psychiatry, 2-205 MEB, Iowa City, IA 52242, USA. william-coryell@uiowa.edu
authors.forename: William
authors.initials: W
authors.lastname: Coryell
authors.forename: Lilian
authors.initials: L
authors.lastname: Dindo
authors.forename: Abby
authors.initials: A
authors.lastname: Fyer
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
mesh_terms: D000328:Adult; D001007:Anxiety / Q000453:epidemiology / Q000523:psychology; D002245:Carbon Dioxide / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006935:Hypercapnia / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009497:Neurotic Disorders / Q000453:epidemiology / Q000523:psychology; D010147:Pain Measurement; D016584:Panic Disorder / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D010555:Personality Inventory; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk; D012307:Risk Factors; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D002245:Carbon Dioxide