Association between serotonin-related genetic polymorphisms and CCK-4-induced panic attacks with or without 5-hydroxytryptophan pretreatment in healthy volunteers.

Genetic regulation of the function of serotonin (5-HT) may be important for the neurobiology of panic disorder. In order to evaluate the influence of 5-HT-related gene variants on the vulnerability to panic attacks, we genotyped 32 healthy volunteers who participated in the study of the effect of 5-hydroxytryptophan on panic attacks induced with cholecystokinin tetrapeptide (CCK-4). The polymorphisms of interest included those of 5-HT transporter (5-HTTLPR) and monoamine oxidase A (MAO-A promoter region) genes. The results showed significant associations between certain genotypes and panic rate in females but not in male volunteers. Specifically, there was a significantly lower rate of CCK-4-induced panic attacks in female subjects who had MAO-A longer alleles or 5-HTTLPR short allele gene variants. These data suggest that functional genetic polymorphisms of the 5-HT system may influence the vulnerability to panic attacks and add to the growing evidence of inhibitory function of 5-HT in the neuronal circuitry of panic.