Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always "on" but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS) states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.
Keywords: chronic stress; default stress response; early life adversity; generalized unsafety; loneliness; low social status; natural versus urban environment; perceived safety; somatic disease; stress theory.