RELATIONSHIP BETWEEN RESPIRATORY, ENDOCRINE, AND COGNITIVE-EMOTIONAL FACTORS IN RESPONSE TO A PHARMACOLOGICAL PANICOGEN

Background: The cholecystokinin agonist pentagastrin has been used to study panic attacks in the laboratory and to investigate hypothalamic-pituitary-adrenal axis activity. Its mechanism of panicogenesis remains unclear. Data from other models suggest that respiratory stimulation itself may induce panic, but pentagastrin's effects on respiration are not well established. Data from another model also suggest links between respiratory and HPA axis reactivity and cognitive modulation of both. To further explore these phenomena, we added respiratory measures to a study of cognitive modulation of HPA and anxiety responses to pentagastrin. Methods: Healthy subjects received pentagastrin and placebo injections, with measurement of cortisol and subjective responses, on two different laboratory visits. They were randomly assigned to receive standard instructions or one of two versions of previously studied cognitive interventions (to either facilitate coping or increase sense of control), given before each visit. Capnograph measures of heart rate (HR), respiratory rate (RR), and end-tidal pCO(2) were obtained on 24 subjects. Results: Relative to placebo, pentagastrin induced a significant decline in pCO2 with no change in RR. Cortisol and HR increased, as expected. Cognitive intervention reduced the hyperventilatory response to pentagastrin. Conclusions: Pentagastrin stimulates respiration, likely via increases in tidal volume. Respiratory stimulation could play a role in its panicogenic potency, though perhaps indirectly. As with HPA axis responses, higher-level brain processes may be capable of modulating pentagastrin-induced hyperventilation. This model may be useful for further study of cortical/cognitive control of interacting emotional, respiratory, and neuroendocrine sensitivities, with potential relevance to panic pathophysiology. Depression and Anxiety 27:1011-1016, 2010. (C) 2010 Wiley-Liss, Inc.