In response to PA-17-493, Addressing Chronic Wound Trajectories Through Social Genomics Research (R21), this application seeks to advance social genomics research by exploring psychosocial stressors, symptoms and biomarkers in a chronic wound population. The most common type of chronic wound is a venous leg ulcer (CVLU), which accounts for 70-80% of the 6.5 million wounds currently being treated in the U.S. at health care costs approaching $25 billion. One of the most common psychosocial stressors is loneliness, which affects 68% of individuals with CVLUs, negatively influencing social relationships and reducing quality of life. Unfortunately, psychosocial stressors are rarely assessed or managed during clinical encounters, and may play a predominant role in the chronic, non-healing state. Loneliness has been linked to systemic inflammation through various molecular pathways such as the upregulation of inflammatory genes. Inflammation is also a well-established biological pathway associated with poor healing suggesting inflammation is a common molecular mechanism that underlies both loneliness and poor wound healing. However, the confluence of loneliness and inflammation in a wound population has not been elucidated. Thus, we hypothesize that substantially heightened inflammation is a common molecular mechanism with a distinct profile that underlies both loneliness and poor wound healing in a chronic wound population compared to a wound population without loneliness. In this application, using a social genomics framework guided by the psychoneuroimmunology (PNI) paradigm and the conserved transcriptional response to adversity (CTRA) model, the aims of our prospective observational longitudinal study are to: examine whether psychosocial stressors (i.e., social isolation, social support) and symptoms (i.e., fatigue, pain, depression, anxiety, sleep disturbance, reduced QOL) differ between lonely (L+) and non-lonely (L-) patients with CVLUs using well-validated questionnaires; characterize a biomarker (chemotaxic factors, growth factors, vascular damage and immune regulators) profile common to L+ and CLVU using well-established RNA sequencing and PCR methods for whole blood samples; and, explore whether age and sex/psychological stressors and symptoms indicate potential moderation/mediation of the effect of loneliness on the biomarker profile, over a 3-month study period, collecting data at 3 time points during wound care. We will also explore demographic and other variables such as age (60 ? 74, ?75 years), sex, chronic illnesses, cognition, health status, functional activity, stigma, nutritional status, length of time to heal (healing trajectory), and wound treatment type across the 3 time points. The long-term objective of this research to better understand molecular mechanisms common to loneliness and inflammation towards development of a biopsychosocial prognostic indicator of healing potential in persons with chronic wounds.
This application addresses a highly prevalent clinical problem - chronic venous leg ulcers (CVLUs) that affect millions of individuals worldwide, causing considerable suffering, disability and poor quality of life. The objective of this exploratory project is to assess stressors, symptoms and biomarkers associated with lonely and non-lonely individuals with CVLUs. Findings are expected to improve understanding of molecular mechanisms common to loneliness and inflammation towards development of a biopsychosocial prognostic indicator of healing potential in persons with chronic wounds.