Abuse and other forms of stress experienced in childhood or even in utero put children at increased risk for health problems in adulthood. In fact, there are several anatomical and functional abnormalities in the brains of abused children.
For example, in abused children, there is a reduced size of the hippocampus – a key structure for memory – and abnormal activity in the amygdala – the brain structure involved in controlling emotions. And reduced activity in several anterior brain regions, particularly in the anterior cingulate cortex, specifically in its rostral part, which is a true regulatory interface to the amygdala.
However, the studies have also revealed changes in DNA. These include a shortening of telomeres – the “caps” at the ends of chromosomes that preserve the integrity of our gene pool. More importantly, there are changes in the expression of certain genes that are thought to affect the pathways that regulate emotions and stress.
Reversible and transmissible changes
The term “epigenetics” refers to changes that do not affect DNA sequences – such as mutations – but influence gene activity. These changes are induced by the environment in response to various signals.
Specifically, epigenetic modifications are biochemical changes to DNA or the proteins around which it is wrapped in the cell nucleus (histones). These changes (e.g. addition of a methyl group) modify the accessibility of genes and hence their readout and ultimately the production of the corresponding proteins. Other epigenetic regulatory systems involve small RNA molecules capable of inhibiting the production of a particular protein.
Unlike mutations, which alter the sequence of the DNA molecule, epigenetic modifications are reversible. But like mutations, they can be inherited during cell divisions and thus passed on to offspring.
Complementing the slow process of genetic selection, these epigenetic mechanisms allow us to respond to environmental changes in the broadest sense – be it climate, diet, smoking, etc., or a negative social context.
Epigenetic changes under stress
Negative life events can permanently alter the expression of certain genes, leading to physical or mental health problems. It is thought that chronic exposure to stress hormones in abused individuals can lead to epigenetic changes associated not only with increased stress reactivity but also with cognitive, emotional, and behavioral disturbances. There is evidence that these disorders can start very early, in utero.
In animals, maternal exposure to stress or toxins during the prenatal period can be traced in the offspring at the epigenetic level. It can be suspected that in such cases the risk of the offspring developing anxiety disorders is increased.
Studies of people born during periods of famine – as in the Netherlands in the winter of 1944-1945 – show the consequences of malnutrition over several generations. This is an example of how prenatal stressors that cause epigenetic changes are metabolic in nature. There is an increased risk of mood disorders in children whose mothers were exposed to starvation during pregnancy. In this case, maternal anxiety could play a role.
Relationship between epigenetic changes and mental disorders
Most epigenetic studies of child maltreatment have found changes in humans that are similar to those observed in animals. The first epigenetic changes identified involved the expression of the NR3C1 gene. This contains the instructions for glucocorticoid receptor production – substances that are released when danger is perceived through activation of the hypothalamic-pituitary-adrenal axis (cortisol).
The NR3C1 gene modification, initially discovered in the brain of rats with low levels of maternal care, was soon identified in human brains in postmortem studies. Specifically, it was identified in suicide victims with a history of childhood abuse. This observation demonstrated for the first time in humans the influence of early traumatic situations on the expression of a gene that is central to the stress response.
A few years later, researchers identified the same epigenetic change in children who had been abused and had various psychological disorders: borderline personality disorder, depressive disorder, and post-traumatic stress disorder.
The modification of the NR3C1 gene consisted of methylation. Their results showed that this methylation not only correlated with the presence of sexual assault but also that it was more important the more severe the abuse and the more frequent the abuse.
For the researchers, this finding suggests that early events may have a lasting influence on the hypothalamic-pituitary-adrenal axis and may explain the emergence of more or less long-term psychopathological disorders.
Changes transmitted to children
In addition to the NR3C1 gene, another gene the FKBP5 gene is often cited in the stress response and, perhaps, in the development and maintenance of various psychological disorders. The FKBP5 gene encodes for a protein that regulates the glucocorticoid receptor, whose affinity for cortisol increases with moderate stress and decreases with intense or repeated stress.
Epigenetic changes in this gene were examined closely in a small number of Holocaust survivors and their children, and compared with two age-matched control groups. Rachel Yehuda’s team showed that the trauma of the concentration camp experience was a major factor in the methylation of the FKBP5 gene. But the real surprise was the discovery of the existence of an identical phenomenon (albeit to a lesser extent) in the children of these Holocaust survivors – children who were brought into the world long after the period of the holocaust!
Thus, it was shown that there is a link between the traumatic experience of the parents, prior to the conception of the child, and the presence of epigenetic changes in both the exposed parent and the offspring. Furthermore, it was found that in children whose parents had experienced the Holocaust, the methylation process was more significant when only the father suffered from post-traumatic stress.
Plasticity of epigenetic
All in all, epigenetics confirms the intuition of all clinicians: a patient’s psychopathological problems can only be understood by looking at them from a historical and developmental perspective. Past traumas are therefore risk factors, which may reinforce the subsequent development of psychological and also physical pathologies.
From this perspective, however, it should be noted that, at least in animals, epigenetic changes associated with early life stresses are potentially reversible. Contextual adaptation could mitigate or even correct them: for example, a rich and stimulating environment (affectively, cognitively, and relationally) at puberty could reverse the negative effects of a lack of maternal care during childhood in adults.
The great plasticity of epigenetic fingerprints and their sensitivity to environmental factors also provide a biological basis for the idea that nothing is ever permanently fixed. In this regard, human studies seem to show that psychotherapy is a beneficial form of environmental regulation.
Rachel Yehuda’s team offered exposure psychotherapy to a number of veterans suffering from post-traumatic stress disorder. Blood samples were taken before treatment and 12 weeks later to monitor the methylation status of the N3C1 and FKBP5 genes.
The results showed that psychotherapy helped not only in treating the patients in terms of perceived health but also in regulating and repairing the epigenetic changes that were caused by the trauma. These initial observations certainly need to be repeated and validated in more patients. However, they carry a message of hope, based on the possibility of using epigenetic to repair the damages caused by previous trauma.