A Social Genomics Model to Explore Loneliness and Systemic Inflammation in an Older Adult Population with Chronic Venous Leg Ulcers

探索患有慢性静脉腿部溃疡的老年人群的孤独感和全身炎症的社会基因组学模型

• 批准号: 10056870
• 负责人: Teresa J Kelechi
• 金额: $ 23.73万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056870
• 关键词: Address; Affect; Age; Age-Years; Anti-Inflammatory Agents; Anxiety; Atherosclerosis; Biological; Biological Markers; Biological Response Modifiers; Blood Vessels; Blood specimen; Cardiovascular Diseases; Chronic; Chronic Disease; Clinic; Clinic Visits; Clinical; Cognition; Cytokine Signaling; Data; Development; Diabetes Mellitus; Distress; Elderly; Exhibits; Fatigue; Future; Gene Abnormality; Gene Expression; Gene Family; Genes; Genetic Transcription; Growth Factor; Health Care Costs; Health Status; Hypothalamic structure; IL6 gene; Immune; Individual; Inflammation; Inflammatory; Leg Ulcer; Length; Link; Literature; Loneliness; Longitudinal observational study; Matrix Metalloproteinases; Mediating; Mediation; Mental Depression; Meta-Analysis; Methods; Modeling; Molecular; National Institute of Nursing Research; Nutritional status; Outpatients; Pain; Pathologic Processes; Pathway interactions; Patients; Pattern; Persons; Physiological; Pituitary Gland; Play; Population; Prognostic Marker; Psychoneuroimmunology; Psychosocial Factor; Public Health; Quality of life; Questionnaires; Research; Role; Sleep disturbances; Social isolation; Social support; Symptoms; TGFB1 gene; TNF gene; Time; Ulcer; Up-Regulation; Vascular Endothelial Growth Factors; Venous; Visit; Whole Blood; biological adaptation to stress; biopsychosocial; chronic wound; clinical encounter; cytokine; disability; healing; immunoregulation; improved; link protein; mortality; prospective; psychological stressor; psychological symptom; psychosocial; response; sex; social genomics; social relationships; social stigma; specific biomarkers; stressor; symptom science; telomere; transcriptome sequencing; wound; wound care; wound healing; wound treatment

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 wounds.

项目总结/文摘