A major question in the biology of stress and environmental adaptation concerns the neurobiological basis of how neuroendocrine systems governing physiological regulatory mechanisms essential for life (metabolism, immune response, organ function) become harmful. The current view is that a switch from protection to damage occurs when vulnerable phenotypes are exposed to adverse environmental conditions. In accordance with this theory, sequelae of early life social and environmental stressors, such as childhood abuse, neglect, poverty, and poor nutrition, have been associated with the emergence of mental and physical illness and an increased risk of common metabolic and cardiovascular diseases later in life. Evidence from animal and human studies investigating the associations between early life experiences (including parent- infant bonding), hypothalamus- pituitary-adrenal axis activity, brain development, and health outcome provide important clues into the neurobiological mechanisms that mediate the contribution of stressful experiences to personality development and the manifestation of illness.
Mounting evidence indicates that the maintenance of chromatin architecture is essential for normal human development and cognitive function. The ATRX gene, which is essential for normal growth and cognitive development, encodes a chromatin- remodeling protein that is expressed in developing neural structures, including newly- born cortical and hippocampal neurons. We have shown that maternal care influences gene programmes, including forebrain ATRX gene expression, and is associated with stable individual differences in learning and memory and anxiety- related and social behaviour, as well as cortical and hippocampal function in adult rodents. These results suggest the possible involvement of ATRX in somatic behaviour in response to maternal care. Since disruption of ATRX impairs cognition and motor functions, inhibits learning in mouse pups, and contributes to developmental silencing of imprinted genes that shape somatic growth and brain, we hypothesize that the effects of mother-offspring interactions during the first week of postnatal life on ATRX expression influences epigenetic programmes that underlie cognitive and emotional development.
The elucidation of the mechanisms involved in the effects of maternal behaviour addresses perhaps the most challenging question in development: How are experiences occurring in early life rendered permanent? In the case of sustained changes in gene expression in brain cells, we can begin to understand the neurobiological basis for individual differences in personality and cognition, which has immense implications for understanding phenotypic differences in nature.