The Conserved Transcriptional Response to Adversity: Prepared for Social Determinants of Health in Surgery

Introduction

Beginning in 2007, a series of RNA profiling studies found that human beings who were exposed to adverse social conditions for extended periods of time showed a recurrent pattern of alterations in immune cell gene expression. ^, This pattern was characterized by increased expression of genes involved in inflammation (e.g., IL1B , IL6 , IL8/ CXCL8 , COX2/ PTGS2 , and TNF ) and decreased expression of genes involved in type I interferon–mediated innate antiviral responses (e.g., IFI- , MX- , and OAS- family genes). This same general pattern was observed across a variety of adverse social conditions such as loneliness, poverty, bereavement, and chronic stress, as well as in subsequent animal models that experimentally manipulated social adversity. The consistency of these gene regulatory alterations across species and across different forms of adversity led to its characterization as a Conserved Transcriptional Response to Adversity (CTRA). Subsequent research has linked the CTRA to an array of chronic disease processes and health outcomes as well differential responses to medical and surgical therapies. This chapter reviews the CTRA's discovery and theoretical conceptualization, early laboratory analyses mapping its biological mechanisms, and more recent studies assessing its role in mediating social disparities in disease risk and treatment responses (including surgical and transplant outcomes). This chapter also highlights emerging behavioral and pharmacological interventions to block CTRA-mediated health risks, surveys some key issues in CTRA measurement, and summarizes several areas of ongoing CTRA research.