Long-term effects of early-life adverse events: the role of sex differences

Exposure to stress represents a well-known risk factor for psychiatric diseases. However, the timing of life stress may be important in determining its long-term outcomes. Growing evidence has demonstrated that experiencing early-life adverse events, especially in the prenatal and adolescent periods, can interfere with neurodevelopmental trajectories, which may result in altered vulnerability to stress-related disorders later in life. Literature data suggest that women present a greater risk to develop psychiatric diseases than men, and this seems to be influenced by the effects of sex hormones on the stress-response system. However, the mechanisms underlying these gender differences remain unclear due to the paucity of both clinical and preclinical studies carried out in female subjects. Therefore, in this talk I will discuss how early-life adverse events might produce different stress-responses in male and female adult rats. In particular, I will present data demonstrating that early-life stressors (prenatal stress or repeated brief social isolation stress during early-adolescence) induced behavioral alterations on emotionality and cognitive functions in the long-term and that these effects are sex divergent. Thus, our findings are relevant to future research aimed not only at investigating sex-differences in the neurobiology of stress-related disorders, but also at evaluating pharmacological interventions to treat long-term alterations induced by early-life stressful events.