The prevailing paradigm used by most researchers and physicians to understand depression appears myopic and deficient, and the treatments derived from it are ineffective. A broader perspective is required for understanding why people in contemporary societies are vulnerable to chronic depression. Evolutionary psychoneuroimmunology synthesizes insights from evolutionary biology, evolutionary psychiatry, neuroscience, immunology, and psychology to provide a broad scientific framework for understanding the relatively high prevalence of depression in people with contemporary western lifestyles. A range of findings indicates that the mismatch between the environments in which Homo sapiens evolved and the environments it currently habits – characterized by sedentary lifestyles, obesogenic diets, fragmented communities, loneliness – contributes in several ways to depression prevalence in contemporary societies. Understanding depression in contemporary Homo sapiens requires not just analyzing the proximate mechanisms contributing to it, such as chronic stress, poor diet, and low-grade systemic inflammation, but also the evolutionary question of why a mind that has undergone hundreds of thousands of years of evolution can be so vulnerable to such severe and debilitating mental health problems. Tinbergen’s four questions, a fundamental conceptual framework used in ethology, evolutionary biology, and evolutionary psychology, organizes these different levels of analysis in a coherent framework for this book.

Societies differ in their inhabitants’ mental well-being. Many affluent and democratic countries, such as the UK and Australia, rank significantly lower in mental well-being than many developing countries, such as Tanzania and Dominican Republic. Many societal factors can either decrease or improve the mental well-being of the people living in those societies. Much of the contemporary burden of depression arises from an evolutionary mismatch between human psychobiology and contemporary western lifestyles characterized by chronic stress, social fragmentation, physical inactivity, circadian disruption, and ultraprocessed diets. These conditions promote low-grade systemic inflammation and dysregulate evolved mood-regulation systems. However, there are measures that societies can implement to address these issues. These include providing safer and more stimulating childhood environments; promoting healthy lifestyles through various policy measures; refining societal values from status competition toward eudaimonia; using evolutionary psychology and biophilic design in urban planning; and giving more opportunities for individuals to discover their ikigai, “a reason for being.” More broadly, not all cultural and technological innovations are inherently negative for human health and well-being. It would be sensible to take advantage of the best parts of these innovations and developments while continuously acknowledging the core constituents of a well-led and fulfilling life.

Low-grade systemic inflammation and neuroinflammation are implicated in the development and maintenance of some cases of depression. This chapter explores the evolutionary psychoneuroimmunological pathways characterizing the inflammatory pathogenesis of depression. The strongest evidence for the link between inflammation and major depressive disorder comes from studies in humans and other animals that have found that the activation of the immune system by immune challenges or by the administration of proinflammatory cytokines induces symptoms of depression in individuals without any previous mental disorders. An estimated 34% of the adult US population have low-grade systemic inflammation. As many as 27% of depressed patients may be affected by neuroinflammation. Low-grade systemic inflammation and neuroinflammation appear to be evolutionarily novel and likely maladaptive pathophysiological outcomes caused by contemporary western lifestyles – most notably by such factors as contemporary western diets, obesity, visceral fat, gut dysbiosis, and chronic stress. Inflammatory states may cause symptoms of depression because the increase of proinflammatory cytokines can lead to the body reacting to it as it does with infection: to produce sickness behaviors that help save energy so that the immune system can overcome the infection, which in this case is not an infection but a more chronic lifestyle-driven inflammatory state.