Investigation of cholecystokinin system genes in panic disorder

Mol Psychiatry. 1999 May;4(3):284-5. doi: 10.1038/


There is evidence for the role of the cholecystokinin (CCK) neurotransmitter system in the neurobiology of panic disorder (PD). The CCK receptor agonist, CCK-tetrapeptide (CCK-4) fulfills criteria for a panicogenic agent and there is evidence that PD might be associated with an abnormal function of the CCK system. For example, PD patients show an enhanced sensitivity to CCK-4, and exhibit lower CSF and lymphocyte CCK concentration as compared to healthy controls (reviewed by Bradwejn et al.). Also, untreated PD patients display an increased CCK-4-induced intracellular Ca2+ mobilization in T cells relative to treated PD, depression and schizophrenia. The CCK receptors have been classified into two subtypes: CCK-A and CCK-B. We report here a study of polymorphisms in the CCK pre-pro hormone gene (CCK), CCK-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 it in our sample, with negative results. A single nucleotide polymorphism has been found in the coding region of the CCK-B receptor gene (CCK-BR) and D Collier (personal communication) identified a highly polymorphic dinucleotide (CT)n microsatellite in the 5' regulatory region. For the CCK-B receptor gene polymorphism, PD patients showed a significant association. Our genetic dissection of the CCK system thus far suggests that the CCK-B receptor gene variation may contribute to the neurobiology of panic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cholecystokinin / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Panic Disorder / genetics*
  • Polymorphism, Genetic
  • Promoter Regions, Genetic*
  • Receptor, Cholecystokinin A
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin / genetics*
  • Reference Values
  • Repetitive Sequences, Nucleic Acid


  • Receptor, Cholecystokinin A
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • Cholecystokinin