Perinatal Epigenetic Programming of Functional Brain Circuits

The “Developmental Origins of Health and Disease” (DOHaD) hypothesis postulates that specific environmental influences during critical pre- and early postnatal phases "shape" or "programme" the formation of an individual's functional phenotype. Exposure to suboptimal nutritional conditions, substance abuse or maternal stress and infections may have a negative impact on development and thus increase the risk for different diseases and disorders at later life. On the other hand, favourable environmental conditions at early development are essential to induce adaptive processes that may help an individual to life successfully and survive in its later life environment. Increasing evidence reveals that these programming mechanisms are mediated by epigenetic mechanisms, thus epigenetics provide the crucial interface between genetic predispositions and the programming influences of the environment. Epigenetically mediated (re-)programming processes are also a hallmark of functional brain maturation, since most neurodevelopmental trajectories start during gestation and continue into early postnatal life and thus are particularly sensitive to environmental influences. Deleterious programming effects that end up in dysfunctional brain circuits increase the risk for mental disorders, psychopathologies or cognitive deficits. However, depending on the type, duration and developmental time-point of the programming environmental influence, “healthy” adaptive processes in the brain may occur promoting resilience and improved stress coping. This book article explains the main concepts of early-life programming and summarizes major findings with respect to the environmentally driven development of functional brain circuits and its underlying epigenetic mechanisms.