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Basic mechanisms of, and treatment targets for, stress-related disorders

The response to the social and physical environment involves two-way communication between the brain and the body and epigenetic adaptation (‘allostasis’) via mediators of the cardiovascular, immune, metabolic, neuroendocrine, and neural mechanisms. Chronic stress causes wear and tear on the brain and body (‘allostatic load and overload’), reflecting also the impact of health-damaging behaviours and lasting effects of early life experiences interacting with genetic predispositions. Hormonal and other mediators of allostasis promote adaptation in the short run but cause allostatic load/overload when they are overused or dysregulated. The brain is key because it determines what is threatening and the physiological and behavioural responses, while showing structural remodelling that affects its function. Besides pharmaceuticals, there are ‘top–down’ interventions, like physical activity, that engage ‘the wisdom of the body’ to change itself, as well as the impact of policies of government and business that encourage individuals to manage their own lives and promote increased ‘healthspan’.