Cortisol reacts with numerous intracellular GRs (Table 11.2) to exert diverse biologic actions (see Chapter 21). Cortisol regulates many functions, including arousal, cognition, mood, sleep, metabolism, maintenance of cardiovascular tone, the immune and antiinflammatory responses, and growth and reproduction.

A clear example of the effects of chronic psychosocial stress in adults is burnout, a syndrome associated with a number of negative consequences to workers’ well-being and health. Uncontrolled work stress is a significant predictor of adverse physical consequences, including hypercholesterolemia, type 2 diabetes, coronary heart disease, and hospitalization caused by a cardiovascular disorder, musculoskeletal pain, changes in pain experiences, prolonged fatigue, headaches, gastrointestinal issues, respiratory problems, severe injuries, and early mortality at age younger than 45 years. Potential mechanisms contributing to burnout include dysregulation of the HPA axis and ANS, which are accompanied by impaired immune function and inflammation.47 These interrelated stress systems increase the risk of adopting poor health choices (e.g., smoking, lack of physical activity and sleep, bad eating habits) that make the individual vulnerable to infectious disease, such as flu-like illnesses, the common cold, and gastroenteritis.

The resultant inability to control inflammatory cells in the brain has the potential to impair adaptive brain functions. Stress-induced inflammation by microglia disrupts corticoamygdala and corticobasal ganglia neural circuits that balance positive and negative states, and predisposes people to negative thinking and to engage in self-medicating behaviors such as smoking, drug use, and consumption of high-fat diets. Repetitive negative thinking has been linked to the development of dementia (see Emerging Science Box: Repetitive Negative Thinking is a Risk Factor for Alzheimer Disease). Depression has been linked to stress-induced inflammation.11,12,30 This link may explain the high prevalence of depression in association with other chronic inflammatory conditions such as heart disease (see Emerging Science Box: Stress and Inflammation Are Causal Factors Linking Heart Disease with Depression).