Childhood trauma leaves its mark on the DNA of some victims

Gene-environment interaction causes lifelong dysregulation of stress hormones

December 02, 2012

Maltreated children are at severe risk of developing anxiety and mood disorders, as the high stress they are subjected to can lead to permanent changes to their gene regulation. Scientists from the Max Planck Institute of Psychiatry in Munich have now documented for the first time that some variants of the FKBP5 gene can be epigenetically altered by early trauma. In people with this genetic predisposition, a trauma causes lasting dysregulation of the stress hormone system. As a result, those who are affected find themselves less able to cope with stressful situations throughout their lives, which frequently leads to depression or anxiety disorders in adulthood. Doctors and scientists hope these discoveries will yield new treatment strategies tailored to individual patients as well as increased public awareness of the importance of protecting children from trauma and its consequences.

Many human illnesses arise from the interaction of individual genes and environmental influences. Traumatic events, especially in childhood, constitute high risk factors for the emergence of psychiatric illnesses in later life. However, whether that kind of early stress actually causes illness in the victim depends largely on his or her genetic predisposition.

Research Group Leader Elisabeth Binder from the Max Planck Institute of Psychiatry examined the DNA of almost 2000 Afro-Americans who had been repeatedly and severely traumatized as adults or in childhood. One-third of trauma victims had become ill and were now suffering from post-traumatic stress disorder. The scientists hoped to cast light on the mechanisms of this gene-environment interaction by comparing the genetic sequence of victims who had not become ill with that of those who had. Their study shows that the risk of contracting post-traumatic stress disorder rises with increasing severity of abuse only in carriers of a specific genetic variant in the FKBP5 gene. FKPB5 determines how effectively the organism can react to stress hormones, and so regulates the entire stress hormone system.

In experiments on neurons, the Munich-based Max Planck scientists were then able to demonstrate that the FKBP5 variant does make a physiological difference to those affected. Extreme stress and the associated high concentrations of stress hormones bring about what is called an "epigenetic change". A methyl group is broken off the DNA at this point, causing a marked increase in FKBP5 activity. This lasting genetic change is generated primarily through childhood traumas. Consequently, no disease-related demethylation of the FKBP5 gene was detected in participants who were traumatized only as adults.

Torsten Klengel, scientist at the Max Planck Institute of Psychiatry, explains the findings of the study as follows: "Depending on genetic predisposition, childhood trauma can leave permanent marks on the DNA and epigenetic changes to the FKBP5 gene augment that effect. The probable consequence is a permanent dysregulation of the victim's stress hormone system, which can ultimately lead to psychiatric illness. Decisive for victims of childhood trauma, however, is that the stress-induced epigenetic changes can only occur if their DNA has this specific sequence."

This recent study improves our understanding of psychiatric illnesses arising from the interaction of environmental and genetic factors. The results will help tailor treatment particularly for those patients who were exposed to trauma in early childhood, thereby greatly increasing their risk of illness.


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