Behavioral and endocrine consequences of early life stress exposure and their impact on adult psychopathology

It is highly recognized that exposure to adversity in early life contributes to pathophysiological processes leading to disease later in life. Children exposed to adverse psychosocial experiences, or early parental loss, are at an increased risk for later depression and metabolic disorders. Preclinical data indicate that epigenetic regulation of gene expression mediates the effects of early life stress (ELS) on adult behavior and health. For example, variations in maternal care in rats trigger life-long differences in stress responsivity involving differences in DNA methylation and histone acetylation of the glucocorticoid receptor in the hippocampus of the offspring. In addition to stress-responsive systems, the expression of neurotrophic factors in the brain may be regulated epigenetically in the context of ELS can contribute to mental health or systemic disease at adulthood. Recently we have set up an animal model of prenatal stress showing that ELS results in a long-term downregulation of the expression of target genes, such as the receptor for glucocorticoids and BDNF, thus mimicking adult conditions characterizing increased risk for psychopathology. Behavioral and neuroendocrine changes accompanying these differences in gene expression suggest increased stress responsivity as well as an increased susceptibility to social stress in periadolescent rats. Results will be discussed taking into account that periadolescence represents both a “window of vulnerability” and a “window of opportunity” for early intervention and for the prevention of adult psychopathology.