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Relationship to Panic Disorder in Parents and Anxiety Disorders in Subjects

Daniel S. Pine, MD; Rachel G. Klein, PhD; Roxann Roberson-Nay, PhD; Salvatore Mannuzza, PhD; John L. Moulton III, PhD; Girma Woldehawariat, PhD; Mary Guardino

Arch Gen Psychiatry. 2005;62:73-80.

Background  Carbon dioxide (CO₂) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO₂ inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders.

Objective  To test in a family-based design whether CO₂ hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents.

Setting and Participants  One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia.

Design and Main Outcome Measures  Parents and offspring received diagnostic assessments. Offspring underwent 5% CO₂ inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO₂ delivery ("threat"), and during CO₂ inhalation. Respiratory rate and volume were measured with spirometry.

Results  No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO₂ sensitivity (panic symptoms and respiratory physiologic response). During CO₂ inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders.

Conclusions  No support was obtained for CO₂ hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO₂ sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.

Author Affiliations: Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, Md (Drs Pine, Roberson-Nay, and Woldehawariat); the New York University Child Study Center, New York University School of Medicine, New York (Drs Klein, Mannuzza, and Moulton); the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY (Dr Mannuzza); and Freedom From Fear, Staten Island, NY (Ms Guardino).

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