Investigation of cholecystokinin system genes in panic disorder

There is evidence for the role of the cholecystokinin (CCK) neurotransmitte r system in the neurobiology of panic disorder (PD).(1) The CCK receptor ag onist, CCK-tetrapeptide (CCK-4) fulfills criteria for a panicogenic agent(1 ) and there is evidence that PD might be associated with an abnormal functi on of the CCK system. For example, PD patients show an enhanced sensitivity to CCK-4 and exhibit lower CSF and lymphocyte CCK concentration as compare d to healthy controls (reviewed by Bradwejn et al.(2)). Also, untreated PD patients display an increased CCK-4-induced intracellular Ca2+ mobilization in T cells relative to treated PD, depression and schizophrenia.(3) The CC K receptors have been classified into two subtypes: CCK-A and CCK-B. We rep ort here a study of polymorphisms in the CCK pre-pro hormone gene (CCK), CC K-AR, and CCK-BR in DSM-IV panic patients (n = 99) vs controls matched for gender and ethnicity. The CCK polymorphism revealed no association with PD. We identified a new polymorphism for the CCK-A receptor gene, and tested i t in our sample, with negative results. A single nucleotide polymorphism ha s been found in the coding region of the CCK-B receptor gene(4) (CCK-BR) an d D Collier (personal communication) identified a highly polymorphic dinucl eotide (CT), microsatellite in the 5' regulatory region. For the CCK-B rece ptor gene polymorphism, PD patients showed a significant association. Our g enetic dissection of the CCK system thus far suggests that the CCK-B recept or gene variation may contribute to the neurobiology of panic disorder.