The Relationships between Adverse Events, Early Antecedents, and Carbon Dioxide Reactivity as an Intermediate Phenotype of Panic Disorder. A General Population Study

Background: Although adverse events have been consistently described to precede and potentially precipitate the onset of panic disorder, there is no information about their ability to alter the individual reactivity to inhaled carbon dioxide, a putative intermediate phenotype of susceptibility to panic disorder. Method: Seven-hundred twelve subjects belonging to the general population-based Norwegian Institute of Public Health Twin Panel underwent a 35% CO2/65% O-2 inhalation challenge test and interview-based lifetime assessments of DSM-IV panic disorder, separation anxiety disorder, childhood parental separation/loss, major life events, adverse events of suffocative nature and common stressful life events. Regression models were applied to predict global subjective anxiety and DSM-IV panic symptoms after 35% CO2/65% O-2 inhalation. Results: The responses to the challenge measured as semicontinuous variables were predicted by symptoms of childhood separation anxiety, childhood parental loss, common stressful events, major life events, suffocative events and the female gender. The role of most of these predictors was confirmed and held true after the exclusion of subjects with lifetime panic attacks/disorder from the analyses. Conclusions: Several factors which have been reported by previous clinical studies to influence the individual susceptibility to develop panic disorder seem to affect the individual reactivity to inhaled carbon dioxide in people from the general population. Some elements of risk may impact simultaneously upon the individual liability to panic and exaggerated sensitivity to hypercapnia. Copyright (C) 2009 S. Karger AG, Basel