לוח שנה משולב

Chronic stress is widely regarded as key risk factor for a variety of diseases, including depression. Yet, while some individuals are vulnerable to stress, others are remarkably resilient. It seems clear that genetic predispositions interact with environmental demands such as chronic stress and modulate its long-term outcome. In addition, there is abundant evidence that environmental circumstances early in life are capable of shaping the adult phenotype. In the last years two seemingly opposing views on early life stress have emerged, the two-hit model and the mismatch model. While the first hypothesis states that aversive experiences early in life predispose individuals to be more vulnerable to aversive challenges later in life, the second hypothesis argues that aversive experiences early in life result in individuals that are better adapted to aversive challenges later in life. There are published data that support either hypotheses, but the interaction with genetic predispositions has rarely been addressed. In my presentation I will propose that both views may be accurate and that the outcome of an early-life stress exposure depend on the genetic background of the individual. In addition, even within the same individual certain phenotypes may be progressively affected by multiple stress exposures (two-hit model), while other phenotypes would be most affected under mismatched conditions. I will illustrate the potential of genetic variations to modulate the outcome of early life adversity and discuss research strategies necessary to address the issue of genetic*development*environment interaction.