Grant: Operating Grant

Panic disorders (PD) affect roughly 5% of the North American population. For reasons that are still unclear, the prevalence of PD in women is 2 to 3 times higher than in men. Clinical manifestations are very diverse; however, PD patients typically display important respiratory symptoms. At rest, PD patients show important respiratory variability and frequent sighing. During a panic attack, patients develop symptoms such as intense air hunger, sweating, heart palpitations, shortness of breath, fear of dying, and hyperventilation. Nearly 100 years ago, clinicians noticed that PD patients were very sensitive to CO2 inhalation. In these patients, CO2 alone can trigger a panic attack. Because this effect is not observed in normal subjects, CO2 sensitivity test is used to diagnose PD. Accordingly, it was proposed that PD patients have an abnormal suffocation alarm system. This hypothesis has stood the test of time and we now know that dysfunction of the neural circuits that regulate breathing is an important part of PD. However, we still do not know what causes this neurological disorder, especially in women. Over the years, we have shown that rats exposed to stress during the neonatal period display the same respiratory abnormalities as PD patients, including an increased sigh frequency and an augmented responsiveness to CO2. Much like humans, these effects are more important in females than males. This proposal aims to exploit this powerful animal model to evaluate the role of sex hormones in this respiratory disorder. We then propose to perform experiments using neuroanatomical, physiological, and pharmacological approaches to 1) identify the brain regions responsible for PD and 2) the neurotransmitter systems involved. We anticipate that the proposed work will generate new knowledge that will be useful for the prevention PD and development of new therapeutic interventions.