Targeting Hypervigilance and Autonomic Arousal: the Psycho-physiologic Model of GERD

GERD affects roughly 20% of the U.S. population and the direct and indirect costs of GERD are substantial, totaling close to 50 billion dollars per year. Evidence supports that a large proportion of this cost and poor clinical outcomes in GERD are related to poor healthcare decisions by both the physician and the patient. The problem of inappropriate GERD management stems from three main issues. First, the disease is heterogeneous and requires treatment informed by a precision model. Second, the current paradigm largely ignores the important brain-gut interactions that drive symptoms and healthcare utilization. Third, there is a paucity of well-performed comparative effectiveness trials focused on assessing treatments beyond acid suppression. The overarching goal of this project over the first two funding cycles primarily focused on the first two problems and we have made major progress developing new physiological predictors of outcome and a more efficient process of phenotyping patients. During the first two cycles, we also determined that psychological distress, in the form of hypervigilance and autonomic arousal, is a major component of patient outcome in GERD. We were able to refute dogma suggesting that there is an inverse relationship between psychological distress and organic disease. Instead, our data proved that hypervigilance was as important as the physiologic perturbations in determining symptom severity and quality of life and these factors were important across the entire spectrum of disease presentation. This work led to the creation of the Psycho-Physiologic Model of GERD that focuses on targeting the primary physiologic abnormality and the important brain-gut interactions driving disease severity. The current competitive renewal will focus on the third problem by performing much needed randomized controlled trials evaluating the effectiveness of behavioral interventions in patients with functional heartburn and refractory GERD. We will use physiomarkers defined during the previous funding cycle to phenotype the patients and use cognitive behavioral interventions to modulate hypervigilance to test the Psycho-Physiologic Model of GERD. Cognitive Behavioral Therapy (CBT) is able to improve hypervigilance and symptom specific autonomic arousal and thus, we will test our theory that CBT can improve outcomes in GERD by targeting these two important psychologic stressors. We will also continue our focus on the interplay of psychology and physiology by determining whether increased mucosal permeability is associated with reflux perception and whether this is modified by hypervigilance and autonomic disruption. This proposal will have a dramatic impact on the field as it will provide important clinical data to guide behavioral treatments in gastroenterology and further define how brain-gut interactions influence symptoms and quality of life in GERD.