A genetically informed study of the association between childhood separation anxiety, sensitivity to CO(2), panic disorder, and the effect of childhood parental loss

Arch Gen Psychiatry. 2009 Jan;66(1):64-71. doi: 10.1001/archgenpsychiatry.2008.513.


Context: Childhood separation anxiety disorder can predate panic disorder, which usually begins in early adulthood. Both disorders are associated with heightened sensitivity to inhaled CO(2) and can be influenced by childhood parental loss.

Objectives: To find the sources of covariation between childhood separation anxiety disorder, hypersensitivity to CO(2), and panic disorder in adulthood and to measure the effect of childhood parental loss on such covariation.

Design: Multivariate twin study.

Participants: Seven hundred twelve young adults from the Norwegian Institute of Public Health Twin Panel, a general population cohort.

Main outcome measures: Personal direct assessment of lifetime panic disorder through structured psychiatric interviews, history of childhood parental loss, and separation anxiety disorder symptoms. Subjective anxiety response to a 35% CO(2)/65% O(2) inhaled mixture compared with compressed air (placebo).

Results: Our best-fitting solution yielded a common pathway model, implying that covariation between separation anxiety in childhood, hypersensitivity to CO(2), and panic disorder in adulthood can be explained by a single latent intervening variable influencing all phenotypes. The latent variable governing the 3 phenotypes' covariation was in turn largely (89%) influenced by genetic factors and childhood parental loss (treated as an identified element of risk acting at a family-wide level), which accounted for the remaining 11% of covariance. Residual variance was explained by 1 specific genetic variance component for separation anxiety disorder and variable-specific unique environmental variance components.

Conclusions: Shared genetic determinants appear to be the major underlying cause of the developmental continuity of childhood separation anxiety disorder into adult panic disorder and the association of both disorders with heightened sensitivity to CO(2). Inasmuch as childhood parental loss is a truly environmental risk factor, it can account for a significant additional proportion of the covariation of these 3 developmentally related phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Administration, Inhalation
  • Adult
  • Anxiety, Separation / diagnosis
  • Anxiety, Separation / genetics*
  • Anxiety, Separation / psychology
  • Arousal / genetics
  • Bereavement*
  • Carbon Dioxide*
  • Child
  • Diseases in Twins / diagnosis
  • Diseases in Twins / genetics*
  • Diseases in Twins / psychology
  • Female
  • Humans
  • Male
  • Panic Disorder / diagnosis
  • Panic Disorder / genetics*
  • Panic Disorder / psychology
  • Phenotype
  • Risk Factors
  • Twins, Dizygotic / genetics
  • Twins, Dizygotic / psychology
  • Twins, Monozygotic / genetics
  • Twins, Monozygotic / psychology


  • Carbon Dioxide