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

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.