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As populations worldwide show increasing levels of stress, understanding emerging links among stress, inflammation, cognition, and behavior is vital to human and planetary health. We hypothesize that inflammation is a multiscale driver connecting stressors that affect individuals to large-scale societal dysfunction and, ultimately, to planetary-scale environmental impacts. We propose a “central inflammation map” hypothesis to explain how the brain regulates inflammation and how inflammation impairs cognition, emotion, and action. According to our hypothesis, these interdependent inflammatory and neural processes, and the inter-individual transmission of environmental, infectious, and behavioral stressors—amplified via high-throughput digital global communications—can culminate in a multiscale, runaway, feed-forward process that could detrimentally affect human decision-making and behavior at scale, ultimately impairing the ability to address these same stressors. This perspective could provide non-intuitive explanations for behaviors and relationships among cells, organisms, and communities of organisms, potentially including population-level responses to stressors as diverse as global climate change, conflicts, and the COVID-19 pandemic. To illustrate our hypothesis and elucidate its mechanistic underpinnings, we present a mathematical model applicable to the individual and societal levels to test the links among stress, inflammation, control, and healing, including the implications of transmission, intervention (e.g., via lifestyle modification or medication), and resilience. Future research is needed to validate the model’s assumptions and conclusions against empirical benchmarks and to expand the factors/variables employed. Our model illustrates the need for multilayered, multiscale stress mitigation interventions, including lifestyle measures, precision therapeutics, and human ecosystem design. Our analysis shows the need for a coordinated, interdisciplinary, international research effort to understand the multiscale nature of stress. Doing so would inform the creation of interventions that improve individuals’ lives; enhance communities’ resilience to stress; and mitigate the adverse effects of stress on the world. 

Stress is a feeling of being worried, scared, or overwhelmed, caused by challenging situations or big life changes. Not all stress is bad, and some kinds of stress, like exercise, can even be good for us. However, when stress is severe or lasts a long time, it can harm our health. Severe stress causes inflammation, which is the body’s way of protecting itself. Inflammation helps the body heal, but long-lasting inflammation can lead to health problems. Stress can also affect the brain, making it hard to think clearly or make good decisions. In our work, we linked all these stress-related factors together (using math) to explain our hypothesis that stress can spread from person to person through our actions, words, and body language—and even over social media—until it affects whole societies and eventually the entire planet! This is a dangerous cycle that can lead to evenmorestress and inflammation, making problems worse. To break the cycle, we each need to focus on reducing stress in our own lives.