How stress in infancy can cause life-long changes to DNA

16 November 2009

A study published last week in Nature Neuroscience has described for the first time a mechanism by which stressful events in infancy can alter gene expression in later life Murgatroyd et al. (2009) 8 Nov epub ahead of print.

The research examined epigenetic changes in mice that had been exposed to stress by being separated from their mothers for three hours a day for the first ten days of their lives. It was already known that this causes alterations in hormone levels and the stress responses of the mice that persist in later life. It was also already known that environmental signals in general can cause epigenetic changes to the genome that alter gene expression, and that these changes are often effected by methylation of DNA. Some previous studies have suggested that this form of altered gene regulation may be a factor in some psychiatric disorders.

This study focused on the expression of two regulatory hormones; arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH), both of which are linked to mood and cognitive behaviours. The researchers found that early life stress in the mice caused a surge in stress-associated hormones, altering the methylation of a regulator of the Avp gene resulting in persistent increased expression of AVP and consequent changes in behaviour, such as deficits in memory and a reduced ability to cope with stress. They also found that these behaviours were mostly reversible by the subsequent use of antagonists to block the mice’s AVP receptors. The authors speculate that the behaviours were likely not entirely reversed because other regulators or genes that they had not targeted were also involved.

Comment: Whilst this study is significant in that it is the first to elucidate a mechanism by which stress can alter gene expression, caution must always be exercised when seeking to extrapolate the results of animal studies to humans. It does however seem highly plausible that environmental stresses in humans could cause similar changes to the epigenome; indeed several studies have suggested such effects, such as the thrifty phenotype observed in the children of mothers who have experienced poor nutrition.

There is an established correlation between childhood neglect and psychiatric illness in humans, and this study suggest the possibility that this may not be a purely psychological effect, but may also be influenced by fundamental changes to the expression of some genes. If this proves to be the case, it could open up research into entirely new approaches to the treatment of psychiatric disorders such as depression.

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