PROJECT SUMMARY/ABSTRACT 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 w...