Adverse experiences early in life can induce long-lasting modifications of physiological functions which may result in an increased susceptibility to the development of psychiatric conditions. However, there are important qualitative and quantitative differences in the outcome of early life stress (ELS), some individuals exposed to ELS are susceptible and develop a pathological condition, while others appear to be resilient. Interestingly, a sub-set of the early stressed individuals may develop a psychiatric condition only if re-exposed to a second stressful event. The transition from adolescence to adulthood, seems to be a crucial period for negative outcomes, but also an important phase for preventive interventions. In this scenario, major challenges concern the definition of specific mechanisms leading to the development of a susceptible state in previously resilient subjects and the identification of specific strategies to normalize the pathological condition induced by the stressful event. Given the ethical and time-related limitations of human studies, animal models represent unique tools of investigation. On these bases, the main aims of this project will be to investigate in rats the persistence until adulthood of alterations induced by ELS and to evaluate if ELS exposure may predispose to psychopathological states in adulthood following a second stressful experience. To address these aims, we will use a prenatal stress model (PNS) obtained by exposing pregnant females to a stressful condition during the last week of gestation. We will then perform specific behavioral investigations at adolescence to identify susceptible and resilient subjects in the obtained male progeny; long-term cognitive and emotional consequences will be tested at adulthood and the effects of a second stressful condition lived at adulthood will be evaluated.
The results of the present study will represent an important step forward in understanding the association between ELS and psychopathology and may allow the identification of biomarkers for the detection of 'the vulnerable period', as crucial stage for the development of psychiatric disorders following traumatic events early in life. The approach adopted in this project will provide new tools for exploring neurobiological alterations that heighten the susceptibility to psychiatric disorders. Moreover, the results of this study will contribute to unravel novel mechanisms underlying the development of resilience to these disorders. Finally, this project will open innovative insights in the discovery of novel therapeutic target, to counteract and to prevent the development of mental disturbances as a consequence of ELS. All in all, this study may have enormous relevance and implications at clinical level, indeed, the possibility to reduce the negative health outcomes of ELS in adulthood may decrease the health care costs associated with mental disorders, saving on welfare payments and substance abuse treatments. And, more importantly, such advancement will ultimately lead to improved functional outcomes for the people suffering from severe mental disorders.