Molecular characterization of the resilient brain: Transcriptional and epigenetic mechanisms. transcriptional and epigenetic mechanisms.

Humans show remarkable variability in their responses to stress. In some individuals, major life stressors precipitate the onset of psychiatric disease, whereas in most others, identical stressors have little to no effect. This phenomenon of individual resistance to stress has been termed resilience. The unique characteristics of resilient individuals have garnered considerable interest, and recent efforts in animal models have attempted to unravel the molecular mechanisms that underlie this phenomenon. These animal studies have identified changes in numerous molecules and pathways spanning multiple brain regions. Although some molecular pathways identified in resilience overlap with those regulated in the opposite direction in stress susceptibility, others are unique to stress-resilient individuals. Hence, the molecular basis of resilience is not merely the absence of susceptibility, but rather an active process, with transcriptional and epigenetic mechanisms demonstrated to play important roles. As pro-resilient molecular alterations counteract the deleterious effects of stress, a better understanding of these processes can potentially pave the way for novel clinical interventions for psychiatric disorders.