Figure 1. Tipping the balance toward neurodevelopmental disease presentation likely depends on multiple interacting factors, ultimately combining a genetic predisposition with environmental insults experienced at key developmental/susceptible periods in life. For example, when mapped onto a given genetic variation that promotes susceptibility, an environmental exposure to prenatal stress may act as a second hit in a two- or three-hit model, where the next stress insult experienced during later points in life tips the scale in the direction of disease onset. In such a model, the prenatal exposure to stress is acting as a point of epigenetic programming due to an increased genetic vulnerability that when added together leads to sensitivity to later life perturbations.