Over generations of epigenetically inherited stress experiences.
Mental problems, which are caused by severe chronic stress in childhood, are inherited epigenetically from generation to generation. This was proven by researchers from the University of Zurich and Swiss Federal Institute of Technology in Zurich.
Programmed mental suffering? Severe chronic stress and trauma in childhood lead to epigenetic changes that are passed on through specific genes over several generations.
Severe chronic stress or traumatic experiences during childhood may cause different psychological episodes, including borderline personality disorders and depression. Neuroscientist Isabelle Mansuy led a team that conducted a study on mice and demonstrated that such late effects can also affect future generations. Mansuy is a professor at both the University of Zurich and the Swiss Federal Institute of Technology in Zurich.
The researchers showed that negative environmental influences in an early stage of life alter the behaviour of an individual throughout his/her life and that this altered behaviour is passed on further, up to the third generation of one’s descendants.
Stress in childhood can lead to problems at a later stage in life.
The scientists used mice in their study. After birth, the young animals would repeatedly be separated from their mother for 14 days at unforeseeable times. During this time, the mother would be subjected to additional stress. This approach causes severe stress in young animals and is used as an animal model to simulate the neglect of children and traumatic childhood experiences. The young mice were affected by this separation so strongly that they became depressive even at an adult age. They were unable to control their impulses and even had social problems under certain circumstances.
In particular, these animals were not able to adequately deal with new or adverse conditions. For instance, they were often irrational when exploring new terrain. They also reacted apathetically or did not fight for their lives under adverse circumstances.
The control group of mice that grew up under natural conditions were defensive in unpleasant situations. They were cautious when exploring new terrain, displaying natural curiosity, but proceeding step by step.
The subject group of traumatized mice did not stop these behavioral disorders throughout their lives and even «passed them on» to their descendants. The researchers also managed to demonstrate that these disorders were evident up to the third generation.
Epigenetics influences behavior
These behavioral changes are not due to genetic mutation. The researchers determined that stress «only» alters the methylation profile of certain genes in the brain and in the sperm of the male mice. This plasticity, which is caused by the changes in the chromatin structure, is referred to epigenetic plane and DNA methylation is a central epigenetic mechanism. «Stress disorients the methylation mechanism», explains Isabelle Mansuy.
In certain genes, methyl, a small molecule consisting of one carbon and three hydrogen atoms, is attached to one of the four building blocks of DNA, the so-called cytosine. However, this does not change the sequence of the four DNA blocks. Nevertheless, the different methylation can, for example, take control over the affected genes and hence influence numerous important body functions.
More or fewer methyl groups
To date, scientists have identified five genes in mice that are affected by early methylation. However, not all the genes that were found were strongly altered. «It largely depends on where, how, and to what extent the methyl groups are attached», adds Mansuy. Some genes had more methyl groups whereas in others, the methyl groups had been excessively removed.
The epigenetic transmission of such behavioral information has long been suspected, but Mansuy’s team is the first to prove this on a molecular level in several generations. They even went a step further and, in collaboration with the Basel pharmaceutical company, Roche, were able to display further genes that are controlled epigenetically and associated with behavioral disorders.
The transfer to people possible?
«The symptoms exhibited by the stressed mice are also very prominent in borderline, depression, and schizophrenic patients», explains Isabelle Mansuy. Thus, the results from the mouse experiment are potentially transferrable to humans.
Mansuy is now planning to extend her study of this epigenetic phenomenon to humans. Here, the team will need tissue samples from individuals and their offspring to find possible methylation candidates based on the genes. «I am convinced that we will also find methylations in human tissue», adds the professor.
The results of the work done by Isabelle Mansuy and her research team are explosive. The publication was therefore difficult due to the caution of many parties in the research community when it comes to acknowledging hereditary transmission of acquired epigenetic changes. However, this concept can help explain many clinical observations. The work was published in the Biological Psychiatry journal. Isabelle Mansuy emphasizes: «We are 100% certain». The team repeated the experiments many times to ensure the observations were consistent. The project lasted over eight years, including all the improvements and additional tasks that were recommended by the reviewers.
Franklin TB, Russig H, Weiss IC, Gräff J, Linder N, Michalon A, Vizi S, Mansuy IM. Epigenetic Transmission of the Impact of Early Stress Across Generations. Biol. Psychiatry, 2010, July 29 (online).