The Icahn School of Medicine at Mount Sinai in Manhattan offered to check anyone who had been in the vicinity of the World Trade Center if they had been exposed to toxins. There were 186 pregnant women who came in for evaluation. A colleague asked if I could help diagnose and monitor the many people who were in shock. They were at risk of developing a mental illness called post-traumatic stress disorder. The fetus was at risk.
The trauma research team trained health professionals to treat the women. We kept an eye on them through their pregnancies. The first sign that the trauma of the World Trade Center attack had reached the uterus was when the babies were small. 38 women and their babies were examined nine months later when they came in for a checkup. Many of the mothers were found to have developed post traumatic stress disorder. Those with post-traumatic stress disorder had low levels of the stress hormone cortisol.
The saliva of the nine-month-old babies of women with post traumatic stress disorder showed low cortisol. Babies whose mothers had been in their third trimester were most affected. We assumed that low cortisol levels in adult children of Holocaust survivors was related to the long-term emotional consequences of being raised by their parents. It appeared that trauma left a trace in offspring even before they were born.
Research has shown that adverse experiences may affect the next generation through multiple pathways. Changes in eggs and sperm may play a role in the most apparent route. Epigenetics involves alterations in the way that genes function. Epigenetics may explain why the effects of trauma may last for a long time after the threat has passed.
The findings suggest that parental trauma can lead to mental health issues. The epigenetic response may be able to help the children of parents who have been through trauma. Is either outcome true?
In the 1990s, my team documented high rates of Post-Traumatic Stress Disorder among Holocaust survivors in my hometown of Cleveland. The first study of its kind, it gained a lot of publicity, and within weeks I was heading a new Holocaust research center at Mount Sinai. The phone was busy. Most of the children of Holocaust survivors called. I studied people like Joseph when I was persistent caller. He said he was a casualty of the Holocaust.
Joseph did not look like a casualty when he arrived for the interview. He could've walked away from the pages of a magazine. Joseph had a vague sense that something bad was going to happen and that he might need to fight for his life. He kept cash and jewelry at hand and became proficient in boxing and martial arts since he was in his 20s. Reports of ethnic cleansing in Bosnia may have triggered his panic attacks.
Joseph's father worked 14 hours a day and never mentioned the war while he was in the U.S. He would wake the family with shrieks of terror from his nightmares. His mother talked about how relatives had been killed in the war. Her son's decision to remain childless enraged her. She said that she didn't survive Auschwitz so that her child wouldn't end the family line. You have a duty to me and history.
Joseph is an adult child of a Holocaust survivor who suffered from anxiety, grief, guilt, and other issues. I need to study people like him. We decided to evaluate the offspring of Holocaust survivors because those who were calling were self-selecting. There was no confusion about the results. Adult children of survivors were more likely to suffer from mood and anxiety disorders. Many Holocaust offspring had low cortisol levels like their parents did.
What do you think it all means? Cortisol and post-traumatic stress disorder have occupied me and many other researchers for decades. The fight-or-flight response was identified in the 1920s as a way for stress hormones to be released. The hormones prompt a cascade of changes, such as quickening the pulse and sharpening the senses to allow the threatened person or animal to focus on and react to the immediate danger. Once the danger subsided, these effects were thought to disappear.
Post-traumatic stress was included in the third edition of the Diagnostic and Statistical Manual of Mental Disorders. It was the first time that trauma had long-term effects. The diagnoses was controversial. Many psychologists believed that its inclusion in the DSM-III had been politically driven and that there were no scientific explanations for how a threat could continue to affect the body after it is removed.
The studies of Vietnam veterans were difficult to understand. According to research done in the 1980's by Earl Giller and John Mason of Yale University, veterans with post-traumatic stress disorder had higher levels of cortisol than patients with other mental illnesses. Many researchers were skeptical of the observations because stress usually causes stress hormones to rise. A year after joining the Yale laboratory, I studied a different group of veterans using other methods to measure cortisol. I replicated the find to my amazement.
I was not sure if the low cortisol levels had anything to do with trauma. Growing up as a rabbi's daughter in a community full of Holocaust survivors, I assumed that the Holocaust was just as bad as the Vietnam War. I told Giller that I was certain that they didn't have any of those things. He said that the hypothesis was a testable one. You should study that instead ofjecturing.
A group of people and equipment landed in Cleveland. We stayed in my parents' house and went door to door interviewing people and taking blood and urine samples at night. Half of the Holocaust survivors had post-traumatic stress disorder, and those with low cortisol. Even if the traumatic experience was a long time ago, it was still a problem.
Why? Which was the first to come? An important clue was found in a 1984 review by Allan Munck and others. Cortisol played a regulatory role in stress hormones. If stress hormones are high for a long time, they can harm the body in a number of ways. Cortisol may have a protective effect in a situation of trauma. It reduces the risk of damage to the brain and organs by shutting down stress hormones. The cortisol might be reset to a lower level.
I placed one of the pieces of the puzzle. Vietnam veterans were more likely to develop post traumatic stress disorder if they had been abused as a child. There was a shape that connected childhood adversity with low cortisol and the possibility of future post traumatic stress disorder. We found that people with lowerCortisol levels were more likely to develop Post-Traumatic Stress Disorder after an attack or accident.
The event that brought them to the emergency room could have caused low cortisol levels. I didn't know what to think. If a person with low cortisol had a traumatic experience, they might not have enough cortisol in their body to deal with the stress reaction. Adrenaline levels might shoot way up, burning the memory of the trauma into the brain, from where it could later surface as nightmares. Low cortisol could be a sign of a vulnerability to developing post traumatic stress disorder.
This was supported by the study of Holocaust children. Even if they did not have their own post traumatic stress disorder, children of Holocaust survivors had low cortisol. Low cortisol seemed to be related to vulnerability to post-traumatic stress disorder.
What is the cause of trauma exposure to low Cortisol? We started a series of studies. Significantly, we found that Vietnam veterans with post-traumatic stress disorder had more of the same substance in their system. cortisol binding to these is what exerts its different influences. A small increase in the cortisol concentration would cause a disproportionate reaction in the body. It wasn't until we looked more closely at the genetics of cortisol functioning that we were able to understand how trauma might affect it.
Scientists realized in the 1990s that the output of our genes is sensitive to factors other than our genes. The templates are provided by genes Like cakes baked using the same ingredients, how much of them get produced depends on the environment. Epigenetics is the study of how genes are expressed. It was important to understand the effects of trauma on the brain and body.
The switches that turn genes on and off are explored by Epigeneticists. A methane molecule that is missing one of its four hydrogen atoms leaves a chemical bond free to attach to another molecule. In the presence of specific enzymes, the methyl groups attach to key sites on a strand of DNA. By occupying these sites like roadblock on a highway, methyl groups can alter transcription, a basic step ingene expression where a piece ofRNA is made from a DNA template Less and increased epigenetics affect the amount of transcription. These changes survive normal cell division and need specificidases to be removed.
One of the first to identify epigenetic changes on stress-related genes of veterans with post-traumatic stress disorder was our group. The effects of trauma were so persistent that alterations were made to explain why. We found that there was a reduction in the amount of methylation in an important region of the genes.
The epigenetic modification suggests that trauma may reset cortisol levels. The stress response is regulated by the body. A rise in cortisol levels may cause the body to produce less of the hormone. The feedback loop might be changed due to the epigenetic changes that occur with trauma. In people who have already been through trauma, their stress systems may be sensitized and their cortisol levels may be low, which could lead to post traumatic stress disorder.
The children of trauma survivors may have some of the same epigenetic changes as trauma survivors. We were told in 2002 that we'd been thinking about some things that weren't right. We assumed that Joseph's problems were caused by the stress in his home. The environment of the uterus appeared to be a factor. The sex of the parent was also affected by the trauma.
We only studied people with two parents who survived the Holocaust. To find out if the sex of the parent mattered, we redid the studies. People who have a mother or father with post-traumatic stress disorder tend to have lower levels of the stress hormone cortisol and more sensitivity to the stress hormone corticosterone. The opposite effect was shown by those whose fathers did not have the disorder.
Holocaust offspring whose mothers or both parents had post-traumatic stress disorder were found to have lower levels of the glucocorticoid receptor genes. The changes mirrored what we'd seen in the survivors themselves. The opposite effect was observed in offspring with only their father's post traumatic stress disorder. There is a chance that stress in mothers and fathers could lead to different epigenetic changes in children.
In a second series of studies beginning in 2016 we looked at the epigenetics of another gene, which is involved in regulating the ability of the cortisol binding factor. The findings showed that both Holocaust parents and their children had the same pattern of epigenetics. It was difficult to find Holocaust survivors who could take part in the study because of the small number.
We were able to extend this work in a much larger sample of Holocaust offspring. Adult children whose mothers were exposed to the Holocaust were found to have lower levels of the epigenetic marker. The effect was not dependent on the mother's post-traumatic stress disorder. She was a child when trauma may have affected her mother's eggs.
Animal studies are often used to explore epigenetic transmission because of the difficulties in studying generations of people. A pathway that ran through sperm was reported by Brian Dias and Kerry Ressler. A male mouse was given an electric shock as it smelled a cherry blossom scent, which caused it to fear the smell. There were changes in the brain and sperm. The male offspring of the shocked mice showed the same fear of cherry blossoms as their female counterparts, but without being exposed to the shock. The effects were passed down. The grandfather mouse taught his son and grandson that the scent of cherry blossom means danger.
In a recent study, my colleagues and I used genome-wide gene expression to identify links between specific conditions and the expression of certain genes. There are distinct patterns of gene expression associated with maternal and paternal trauma exposure.
Trauma, along with altering the eggs and sperm that are part of our genetic inheritance, affects the uterus. The offspring of women who were pregnant during the Dutch Famine, a six-month period during World War II when the Nazis blocked the food supply to the Netherlands, provided an early indicator of in utero effects. The researchers found that the effects of stress and deprivation on metabolism and susceptibility to cardiovascular illness were dependent on the trimester of exposure.
The babies who were born after 9/11 had lower cortisol levels in the womb. I didn't know what this condition meant for their development. The mothers with low cortisol were more likely to say that their nine-month-olds were anxious and afraid of strangers. We didn't have the funds to follow the babies into adulthood.
The uterus may leave a trauma trace in the offspring. Some clues came from our work on Holocaust survivors and their children. The story is complicated again, and this time it involves anidase called 11-beta-hydroxysteroid dehydrogenase type 2. Those who were the youngest during World War II had lower levels of the enzyme than those who had survived the Holocaust. The enzyme is usually found in the body's organs. In the interest of promoting survival, the body can reduce levels of 11-HSD2 under certain conditions. When there is no more food, the level will return in adults, but in children it will remain low. When Holocaust survivors were exposed to long periods of malnourishment, 11-HSD2 levels may have been altered.
The children of Holocaust survivors had higher levels of 11-HSD2 than the control subjects. There is a logic to the results. 11-HSD2 protects the fetus from the effects of maternal cortisol, which can be harmful to the developing brain. Maternal cortisol is converted into an inactive form by the enzyme in the third trimester, creating a protective shield for the fetus from the harmful effects of the hormone. The high levels of this enzyme in the offspring of Holocaust survivors may be an attempt to protect the fetus from the lower levels of 11-HSD2 in their mothers.
The fact that offspring are not always passive recipients of their parents' scars is a result of this. It is possible for offspring to adapt to the impact of their parents' trauma.
Children's development is influenced by how traumatised parents interact with them. One of the most powerful nonfiction accounts of growing up with Holocaust survivor parents was Art Spiegelman's graphic novel, which broke through a cultural barrier and helped others to open up about their suffering. The traumatized family has been examined by many psychologists and neuroscientists, who have found more and more nuances in the story.
Epigenetic alterations in stress-related genes, particularly those reflected in the offspring of traumatised parents, may be markers of vulnerability or a mechanism through which offspring become better equipped to cope with adversity. We're looking at this area.
It's tempting to see epigenetic inheritance as a story of how trauma can lead to permanent damage. The body tries to prepare offspring for challenges similar to those faced by their parents. Changes in circumstances may result in the emergence of novel vulnerabilities. This form of intergenerational transmission depends on the environment encountered by the offspring.
Some of these stress related and intergenerational changes can be reversed. Epigenetic change is reflected in healing. The offspring conceived after the treatment did not have the cherry blossom epigenetic alterations and did not fear the scent. The findings are preliminary and may suggest new avenues for treatment.
As we learn more about how catastrophic experiences have shaped those who lived through them and their descendants, we will be better equipped to face them with resolution and resilience.
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