Heart rate variability as a modifiable biomarker of clinical symptoms and psychological functioning in pediatric patients with inflammatory bowel disease

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PROJECT SUMMARY Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are immune- mediated gastrointestinal disorders associated with chronic medical and psychosocial dysfunction. IBD is increasingly conceptualized as a product of the brain-gut axis, a model that describes the network of communication between the central nervous system (CNS), the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and the gut. Consistent with a brain-gut axis model, patients with IBD demonstrate dysfunction of the ANS indicative of a chronic stress response. ANS functioning can be measured via heart rate variability (HRV), a non-invasive measure suitable for pediatrics. Early evidence suggests that patients with IBD exhibit alterations in HRV consistent with ANS rigidity as well as psychological distress and increased emotional reactivity to stress. These alterations in autonomic functioning are also observed in individuals with anxiety and depressive disorders, and it is well recognized that youth with IBD are at increased risk for developing chronic anxiety and depression. Biofeedback training to treat alterations in HRV has led to improvements in disease symptoms as well as reductions in emotional distress for youth with other chronic gastrointestinal illnesses. The goal of the proposed work is to test the utility of HRV as a biomarker of clinical symptoms as well as symptoms of anxiety and depression in pediatric patients with IBD who are enrolled in a biofeedback therapy program. In this R03 project, I will build on the work of my K23 (K23DK122115) to establish HRV as a clinically relevant and modifiable biomarker that can be reliably used in treatment studies of young patients with clinical symptoms of IBD and related stress, depression, and anxiety. I developed and am currently testing a remote HRV biofeedback-enhanced cognitive behavioral therapy (CBT) treatment program in 40 youth with IBD and symptoms of anxiety and depression. With R03 support we will be able to process the rich but complex raw HRV data obtained at baseline, during biofeedback sessions, and at posttest to evaluate the trajectory of HRV in these youth currently in treatment. The overall goals of the current study are to (1) determine the relationship between baseline HRV and clinical symptoms of IBD, anxiety, and depression in 40 adolescents with IBD and (2) determine if HRV changes with a virtual, biofeedback-enhanced CBT treatment intervention. This R03 offers a source of support for a new avenue of inquiry into HRV as a brain-gut axis mechanism driving chronic psychological distress and clinical symptoms in patients with pediatric IBD. Combined with the outcomes of the K23 research, findings will support a competitive R01 to test efficacy of a biofeedback-enhanced CBT intervention, using HRV as a primary outcome variable and biomarker of clinical improvement.