A segregation study of panic disorder in families of panic patients responsive to the 35% CO2 challenge

Background: A genetic component has a role in the etiology of Panic Disorder (PD) and a familial association between PD and CO2 hypersensitivity have been repeatedly described. Methods: Complex segregation analysis was performed on a sample of 165 families of PD probands and on the subgroup homogeneous for CO2 hypersensitivity, using Regressive Logistic Models. The only relatives considered to be affected were those with PD. Relatives have been diagnosed according to Family History Method. Results: A Mendelian hypothesis was compatible with our data, without distinction between different models of transmission. The Akaike’s Information Criterion values indicated that the Additive model was the most parsimonious, with a gene frequency of .0005, incomplete penetrance and a phenocopy rate of .00029. By subdividing the families according to the probands’ responses to CO2 inhalations, probands of 134 families were hypersensitive to CO2. The analysis performed on this subgroup supported the existence of a SML with a best fit for a Dominant model. Conclusions: A SML account for genetic transmission in PD families and 35% CO2 challenge test may individuate a genetically homogeneous subgroup of patients with PD.