A twin study of the common vulnerability between heightened sensitivity to hypercapnia and panic disorder

Abstract

For unknown reasons the inhalation of CO(2)-enriched air mixtures evokes acute panic-like symptoms in people with panic disorder and in their unaffected relatives. This study was set to determine whether, and to what extent, CO(2)-induced acute anxiety and panic disorder share the same genetic and environmental determinants. Cholesky structural equation models were used to decompose into genetic and environmental elements the correlation between self-assessed anxiety post-35%CO(2)-65%O(2) inhalation and interview-based DSM-IV lifetime diagnoses of panic disorder in 346 young adult twin pairs of the Norwegian Institute of Health Panel, 12% of whom had been invited to take part into the CO(2) study on the basis of self-reported symptoms of anxiety gathered 4-7 years before the provocation challenge. A full model corrected for the partially selective ascertainment showed that the phenotypic correlation between post-CO(2) anxiety and DSM-IV panic was largely due to additive genetic influences, while shared and unique environmental agents concurred to explain a relatively minor proportion of the correlation between these two traits. According to the best-fitting model the genetic correlation between post-CO(2) anxiety and panic was 0.81 (0.50-0.98); a common genetic factor was sufficient to explain the traits' covariation and a further, specific genetic factor was necessary to account for the residual phenotypic variance. The genetic determinants that lead to overreact to a hypercapnic stimulus coincide at a considerable extent with those that influence liability to naturally occurring panic. Environmental factors provide a modest--or no--contribution to the covariation of CO(2)-provoked anxiety with naturally occurring panic.

Temperament, Character and Anxiety Sensitivity in Panic Disorder: A High-Risk Study

“…To our knowledge, this is the first study investigating temperament and character dimensions in a sample of children at high risk for PD, and thus the results should be considered preliminary; we confirm the results of the two previous studies showing no differences in AS between children of patients with PD and those of healthy controls [23,24]. Our findings are in line with previous studies showing that CO 2 hypersensitivity, a familial vulnerability marker for PD with relevant heritable aspects [17,18,19,20], is related neither with temperamental dimensions [4] nor with AS levels [29,30]. Moreover, previous studies suggest that high AS or peculiar temperamental dimensions may be related with a large spectrum of anxiety symptoms or disorders [5,6,7,16], whereas hypersensitivity to CO 2 is specifically linked to panic vulnerability [31,32].…”

“…Family studies suggest that PD runs in families, with a relevant genetic source of the familial risk [1], and that hypersensitivity to CO 2 challenges represents a vulnerability marker for PD in both adult and children first-degree relatives of patients suffering from PD [17,18]. Finally, heritable aspects of CO 2 hypersensitivity and PD seem to overlap significantly [19,20]. Given that both temperament and AS have hereditary components [21,22] and may be linked to the vulnerability to PD, offspring of patients with PD might have peculiar temperament profiles or higher AS.…”

The Relationships between Adverse Events, Early Antecedents, and Carbon Dioxide Reactivity as an Intermediate Phenotype of Panic Disorder

“…As a consequence, the percentage of ‘anxiety-prone’ subjects amongst the 712 twins who underwent the 35% CO 2 /65% O 2 challenge was 20.5%, as compared to 13.5% prevalence in the original NIPHTP MHS sample. The subjects who accepted to participate in the CO 2 study did not differ from those in the original NIPHTP MHS sample for age and frequency of contact with the cotwin [21,22,28]. Moreover, preliminary analyses showed that the frequency of contact with the cotwin, did not influence the post-CO 2 response: regression summary R 2 = 0.001, F 2, 255 = 0.32, p = 0.97; telephone contact: β = –0.006, p = 0.94; personal contact: β = 0.018, p = 0.81.…”

“…While individual differences in the anxious reaction to CO 2 are moderately heritable, environmental factors explain a sizable proportion of variance [21,22] for post-CO 2 subjective anxiety. However, no study has so far been carried out to clarify whether AE predict the response to the CO 2 stimulation per se (i.e.…”

Animal Models of Human Anxiety Disorders: Reappraisal From a Developmental Psychopathology Vantage Point

“…Human studies show that SAD predicts heightened risk to develop PD in adulthood (75,76) and both these conditions are associated with heightened sensitivity to CO 2 (44,77,78). In turn, CO 2 hypersensitivity shares common genetic determinants with both SAD and PD, with childhood parental loss adding a significant contribution to explain covariation (44).…”