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Central Cholecystokinin Activity in Irritable Bowel Syndrome, Panic Disorder, and Healthy Controls

From the Department of Psychiatry, University of Ottawa, and the University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, Ottawa, Ontario, Canada.

Address correspondence and reprint requests to Dr. Diana Koszycki, Stress and Anxiety Clinical Research Unit, Royal Ottawa Hospital, 1145 Carling Avenue, Ottawa, Ontario K1Z 7K4. E-mail: dkoszyck{at}rohcg.on.ca

Objective: Irritable bowel syndrome (IBS) and panic disorder (PD) coexist with a high frequency. However, the nature of this relationship remains obscure. We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin (CCK) system. To test this hypothesis, we assessed whether the enhanced panicogenic response to CCK-tetrapeptide (CCK-4) observed in PD is also present in IBS.

Methods: Eight psychiatrically healthy IBS patients, 8 PD patients with no history of IBS, and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind, randomized fashion.

Results: Consistent with previous findings, panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls. In contrast, IBS patients exhibited a response that was comparable to controls. Interestingly, CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups. No diagnostic difference was noted for cardiovascular response to CCK-4.

Conclusion: These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders. Nevertheless, the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS.

Key Words: irritable bowel syndrome • panic disorder • panic attacks • cholecystokinin-tetrapeptide • gut–brain interaction

Abbreviations: IBS = irritable bowel syndrome; PD = panic disorder; CCK = cholecystokinin; NTS = nucleus tractus solitarius; CBF = cerebral blood flow; NC = normal controls; PSS = Panic Symptom Scale; CCK-4 = cholecystokinin-tetrapeptide; VAS = visual analog scale.