What Doesn’t Kill You Makes You Anxious: The Impact of Early-Life Stress on Vulnerability to Psychopathology in Adulthood

Abstract

Early life stress has been linked to changes in behavior and the physiological stress response as well as an increased susceptibility to psychiatric illnesses such as anxiety and depression in adulthood. Rodent models have been developed to probe the mechanism of such effects; further development of the Maternal Separation with Early Weaning (MSEW) mouse model of early life stress provides the potential to conduct more in depth molecular analyses of the mechanism given the sequencing and detailed annotation of the mouse genome. In rodent models, early life stress has been associated with decreased adult neurogenesis in the hippocampus and increased anxiety. Early life stress has also been associated with changes in interneuron levels and activity in rodent models; these types of changes have been identified in various psychopathological profiles including in depression in humans. These findings raise the question of whether anxiety induced by early life stress is correlated with a similar molecular profile of altered interneuron activity. A new theoretical framework for how early-life stress leads to a greater risk for psychopathology is offered: the Modularity Disruption Hypothesis which suggests that increased functional connectivity between the hippocampus and the prefrontal cortex plays a primary role in early-life stress-induced vulnerability to psychopathology. The proposed work offers testable hypotheses of the mechanism underlying the effects of early adversity and may hold implications for the development of novel therapy techniques for early life stress-associated psychopathology.