[Intrauterine programming of disorders of brain function in later life]

Fetal malnutrition or prenatally enhanced stress hormone levels have the potential to program brain function in later life. Even modest malnutrition has direct effects on brain development mainly via modulation of the insulin-like growth factor system. Nutrient restriction also increases maternal stress hormone concentrations in the fetal circulation. Increased fetal cortisol concentrations due to restricted fetal nutrient supply, prenatal stress or glucocorticoid treatment affect structural and functional brain development. Increased cortisol concentrations during maturation of the fetal hypothalamic-pituitary-adrenal (HPA) axis in the last weeks of pregnancy induce hyperactivity of the HPA axis due to permanent desensitization of glucocorticoid receptors in the hippocampus and a subsequent decrease in negative feedback regulation of the HPA axis. Increased responsiveness of the HPA axis to stress in later life is associated with perturbation of the activity of neurotransmitter systems such as the serotonergic, dopaminergic and GABAergic systems predisposing to discrete cognitive disturbances, behavioral disorders and depressive and schizophrenic diseases.