Abstract
The discovery of stress-hormone receptors in the hippocampal formation has fostered research showing that the brain, including its higher cognitive centers, is the key organ of the response to stressors, in terms of both perception of what is stressful and its ability to determine the consequences of stress for brain and body via the neuroendocrine, autonomic, immune, and metabolic systems. These systems, in turn, are responsible for either successful adaptation or pathophysiology as a result of the cumulative burden of adaptation to stress and maladaptive lifestyle, which is known as "allostatic load." The brain itself is also a target of stress and stress-related hormones, and it undergoes structural and functional remodeling and significant changes in gene expression. These changes are adaptive under normal circumstances but can lead to damage when stress is excessive. The growing recognition of the adaptive plasticity and stress vulnerability of the brain itself, which began with research on the hippocampus, now includes other brain regions such as the amygdala and prefrontal cortex and fear-related memories, working memory, and self-regulatory behaviors. The interactions between these brain regions during the biological embedding of experiences over the life course determines whether events in the social and physical environment will lead to successful adaptation or to maladaptation and impaired mental and physical health, with implications for understanding health disparities and the impact of early life adversity and for intervention and prevention strategies.