title: Early-life risk factors for panic and separation anxiety disorder: insights and outstanding questions arising from human and animal studies of CO2 sensitivity.
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.
authors.affiliation: Department of Psychiatry and Neurosciences, Laval University, Québec, Canada; Centre de Recherche Institut Universitaire en Santé Mentale de Québec, Canada. Electronic address: Marco.Battaglia@fmed.ulaval.ca.
authors.forename: Marco
authors.initials: M
authors.lastname: Battaglia
authors.affiliation: The Academic Centre for the Study of Behavioural Plasticity, 'Vita-Salute' San Raffaele University, Milan, Italy; The Department of Clinical Neurosciences, San Raffaele Hospital, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ogliari
authors.affiliation: CNR, Institute of Cell Biology and Neurobiology/IRCCS Santa Lucia Foundation, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Amato
authors.affiliation: Departement of Pediatrics Laval University, Québec, Canada; Centre de Recherche du CHU de Québec, Hôpital St-François d'Assise Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Kinkead
mesh_terms: D000818:Animals; D001010:Anxiety, Separation / Q000209:etiology* / Q000235:genetics; D002245:Carbon Dioxide / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D016584:Panic Disorder / Q000209:etiology* / Q000235:genetics; D012307:Risk Factors; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics
chemical_list: D002245:Carbon Dioxide
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