Early-life risk factors for panic and separation anxiety disorder: Insights and outstanding questions arising from human and animal studies of CO2 sensitivity

Marco Battaglia, Anna Ogliari, Francesca D'Amato, Richard Kinkead

Research output: Contribution to journalArticle

Abstract

Genetically informative studies showed that genetic and environmental risk factors act and interact to influence liability to (a) panic disorder, (b) its childhood precursor separation anxiety disorder, and (c) heightened sensitivity to CO2, an endophenotype common to both disorders. Childhood adversities including parental loss influence both panic disorder and CO2 hypersensitivity. However, childhood parental loss and separation anxiety disorder are weakly correlated in humans, suggesting the presence of alternative pathways of risk.The transferability of tests that assess CO2 sensitivity - an interspecific quantitative trait common to all mammals - to the animal laboratory setting allowed for environmentally controlled studies of early parental separation. Animal findings paralleled those of human studies, in that different forms of early maternal separation in mice and rats evoked heightened CO2 sensitivity; in mice, this could be explained by gene-by-environment interactional mechanisms.While several questions and issues (including obvious divergences between humans and rodents) remain open, parallel investigations by contemporary molecular genetic tools of (1) human longitudinal cohorts and (2) animals in controlled laboratory settings, can help elucidate the mechanisms beyond these phenomena.

Original languageEnglish
Pages (from-to)455-464
Number of pages10
JournalNeuroscience and Biobehavioral Reviews
Volume46
Issue numberP3
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Anxiety
  • Carbon dioxide challenge
  • Carbon dioxide sensitivity
  • Childhood parental loss
  • Control of breathing
  • Fear
  • Gene-environment interaction
  • Hypercapnia
  • Panic disorder
  • Rodent models
  • Separation anxiety
  • Twin studies

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology
  • Medicine(all)

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