The Resilient Brain: Epigenetics, Stress, and the Lifecourse

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor.  The healthy brain is resilient and responds to experiences over the lifecourse that produce epigenetic changes which result in structural and functional adaptive plasticity from the level of gene expression out to the cell surface.  These changes are mediated in part by circulating hormones as well as by neurally-derived neurotransmitters and neuromodulators, reflecting the two-way communication between brain and body whereby neural activity also regulates the neuroendocrine, metabolic and immune systems. The genetic constitution of an individual sets the limits on what experiences are able to do.  The lifecourse is a “one way stress” in which there is no true reversal but redirection that occurs in response to positive or negative experiences that may be unique to each stage of life.   It is important to remember that experiences even before conception as well as early life experiences can have a lasting impact.   This work has led translationally down a conceptual path, namely, that mediators of adaptation act biphasically – protective in the short run and potentially damaging in the long run – embodied in the now widely used concepts of allostasis and allostatic load/overload. Supported by Hope for Depression Research Foundation.