Prenatal stress, glucocorticoids and the programming of the brain

A large body of human epidemiological data, as well as experimental studies , suggest that environmental factors operating early in life potently affec t developing systems, permanently altering structure and function throughou t life. This process with its persistent organizational effects has been ca lled 'programming', The brain is a key target for such effects. This review focuses on the effects of adverse early environments, notably exposure to stress or glucocorticoids, upon subsequent adult hypothalamus-pituitary-adr enal axis activity, behaviour and cognition. We discuss the effects observe d, the proposed underlying molecular and cellular mechanisms and the conseq uences for pathophysiology. The data suggest that key targets for programmi ng include glucocorticoid receptor gene expression and the corticotrophin-r eleasing hormone system. Increasing evidence for analogous processes in hum ans is also reviewed. Early life programming of neuroendocrine systems and behaviour by stress and exogenous or endogenous glucocorticoids appears to be a fundamental process underpinning common disorders. Approaches to minim ize or reverse the consequences of such early life events may have therapeu tic importance.