Response to 5% carbon dioxide in children and adolescents: relationship to panic disorder in parents and anxiety disorders in subjects.
BACKGROUND
Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) 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 CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents.


METHODS
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.


METHODS
Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) 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 CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) 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 CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.
Pine
Daniel S
DS
Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, MD 20817, USA. daniel.pine@nih.gov
Klein
Rachel G
RG
Roberson-Nay
Roxann
R
Mannuzza
Salvatore
S
Moulton
John L
JL
Woldehawariat
Girma
G
Guardino
Mary
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001008:Anxiety Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology; D002648:Child; D016241:Child of Impaired Parents; D004305:Dose-Response Relationship, Drug; D005819:Genetic Markers; D006801:Humans; D016584:Panic Disorder / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D012307:Risk Factors
D005819:Genetic Markers; D002245:Carbon Dioxide