Cholecystokinin and panic disorder - three unsettled questions

The serendipitously discovered panicogenic effect of the cholecystokinin fr agment, the C-terminal tetrapeptide amide (CCK-4), has suggested that the w idespread network of CCK neurons and corresponding CCK-B receptors in the b rain are in some way involved in pathogenesis panic disorders in man. Two d ecades of research have now established that exogenous CCK-4 in a reproduci ble, dose-dependent and sensitive manner indeed evokes panic attacks in bot h healthy subjects and at even lower doses in anxiety patients. But several questions about the molecular mechanisms by which endogenous CCK peptides may precipitate panic attacks remain to be answered. This review foe-uses o n three immediate questions. (1) Does endogenous CCK-4 exist? (2) Is the pa nicogenic effect mediated only through CCK-B receptors? (3) Are measurement s of CCK peptides in cerebrospinal fluid of use in elucidating the pathogen esis and/or diagnosis? This review concludes that the answers to these ques tions may further the understanding of panic disorder substantially, and he nce contribute to improved diagnosis and therapy of the disease. (C) 2000 E lsevier Science B.V. All rights reserved.