Reappraising Preclinical Models of Separation Anxiety Disorder, Panic Disorder, and CO2 Sensitivity: Implications for Methodology and Translation into New Treatments

  • Marco BattagliaEmail author
  • Waqas Ullah Khan
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 40)


Separation anxiety applies to multiple forms of distress responses seen in mammals during postnatal development, including separation from a caregiver. Childhood separation anxiety disorder is an important risk factor for developing panic disorder in early adulthood, and both conditions display an increased sensitivity to elevated CO2 concentrations inhaled from the air. By interfacing epidemiological, genetic, and physiological knowledge with preclinical animal research models, it is possible to decipher the mechanisms that are central to separation anxiety and panic disorders while also suggesting possible therapies. Preclinical research models allow for environmentally controlled studies of early interferences with parental care. These models have shown that different forms of early maternal separation in mice and rats induce elevated CO2 respiratory sensitivity, an important biomarker of separation anxiety and panic disorders. In mice, this is likely due to gene-environment interactions that affect multiple behavioural and physical phenotypes after exposure to this early adversity. Although several questions regarding the causal mechanism of separation anxiety and panic disorder remain unanswered, the identification and improved understanding of biomarkers that link these mental health conditions under the guise of preclinical research models in conjunction with human longitudinal cohort studies can help resolve these issues.


Acid sensing ion channels CO2 sensitivity Epigenetics Gene-environment interaction Genetics Pain Panic disorder 



The authors would like to thank Dr. Richard Kinkead for the discussion and clarifications regarding his findings relating to the NMS paradigm. Moreover, we would like to thank Myeda Kamal for constructing the figure presented in our chapter.


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Authors and Affiliations

  1. 1.Division of Child, Youth and Emerging Adulthood PsychiatryCentre for Addiction & Mental HealthTorontoCanada
  2. 2.Department of PsychiatryUniversity of TorontoTorontoCanada
  3. 3.School of Medicine, Faculty of Health SciencesTrinity College DublinDublinIreland

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