Posts Tagged ‘cortisol’

18 Jun

Part six: Epigenetic inheritances may represent the body’s attempts to prepare offspring for challenges similar to those encountered by their parents.

Posted by Marty in Assorted. Tagged: , , , .

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“How traumatized parents interact with their children, of course, also influences their development. One of the most powerful nonfiction accounts of growing up with Holocaust survivor parents was Art Spiegelman’s serialized graphic novel Maus; it broke through a cultural barrier, helping others to open up about their suffering. Many psychologists and neuroscientists have examined the traumatized family, finding ever more subtleties, and the story will continue to unfold for decades to come.

An important question is whether epigenetic alterations in stress-related genes, particularly those reflected in the offspring of traumatized parents, are necessarily markers of vulnerability or whether they may reflect a mechanism through which offspring become better equipped to cope with adversity. This is an area we’re actively exploring.

It is tempting to interpret epigenetic inheritance as a story of how trauma results in permanent damage. Epigenetic influences might nonetheless represent the body’s attempts to prepare offspring for challenges similar to those encountered by their parents. As circumstances change, however, the benefits conferred by such alterations may wane or even result in the emergence of novel vulnerabilities. Thus, the survival advantage of this form of intergenerational transmission depends in large part on the environment encountered by the offspring themselves.

Moreover, some of these stress-related and intergenerational changes may be reversible. Several years ago we discovered that combat veterans with PTSD who benefited from cognitive-behavioral psychotherapy showed treatment-induced changes in FKBP5 methylation. The finding confirmed that healing is also reflected in epigenetic change. And Dias and Ressler reconditioned their mice to lose their fear of cherry blossoms; the offspring conceived after this “treatment” did not have the cherry blossom epigenetic alteration, nor did they fear the scent. Preliminary as they are, such findings represent an important frontier in psychiatry and may suggest new avenues for treatment.

The hope is that as we learn more about the ways catastrophic experiences have shaped both those who lived through those horrors and their descendants, we will become better equipped to deal with dangers now and in the future, facing them with resolution and resilience.

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17 Jun

Part five: IN THE WOMB

Posted by Marty in Assorted. Tagged: , , .

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Apart from altering the eggs and sperm that encapsulate our genetic inheritance, sometimes decades before conception, trauma also seems to influence the uterine environment. Meticulous studies of 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, causing widespread starvation—provided an early indication of in utero effects. Researchers discovered that the combined effects of extreme stress and nutritional deprivation, such as deficits in metabolism and susceptibility to cardiovascular illness, depended on the trimester of exposure.

The 9/11 babies were also impacted in the womb, with those in the third trimester having significantly lower cortisol levels. What this condition meant for their future development I sadly never found out. At the wellness visit, mothers who had PTSD (and low cortisol) were more likely to report that their nine-month-olds were unusually anxious and afraid of strangers. But we didn’t get the funding to follow the babies into adulthood.

How might the uterine environment leave a trauma trace in the offspring? Our work on Holocaust survivors and their adult children provided some clues. The story is again complicated, and it involves an enzyme known as 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Holocaust survivors had lower levels of the enzyme than those who hadn’t lived through the Holocaust—and such effects were particularly pronounced in those who were the youngest during World War II. The enzyme is normally concentrated in the liver, kidneys and brain. Under conditions of food deprivation, however, the body can lower levels of 11β-HSD2 to increase metabolic fuel in the interest of promoting survival. In adults, the enzyme level will return to what it was when there is no more starvation, but in children, the level may remain low. Our findings suggested that 11β-HSD2 levels might have been altered during childhood when Holocaust survivors were exposed to long periods of malnourishment; the change persisted well into old age.

In the children of women who were Holocaust survivors, however, we saw quite the opposite: 11β-HSD2 levels were higher than in Jewish control subjects. The result might seem contradictory, but there is a logic to it. During pregnancy, 11β-HSD2 also acts in the placenta, protecting the fetus from exposure to circulating maternal cortisol, which can be toxic to the developing brain. The enzyme, which is particularly active in the third trimester, converts maternal cortisol into an inactive form, creating a kind of chemical shield in the placenta that protects the fetus from the hormone’s harmful effects. The high levels of this enzyme in the offspring of Holocaust survivors may thus reflect an adaptation, an effort to protect the fetus from the lowered 11β-HSD2 levels in their mothers.

All of this means that offspring are not always passive recipients of their parents’ scars. Just as a parent was able to survive trauma by means of biological adaptations, offspring can sometimes adapt to the biological impact of their parents’ trauma.

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16 Jun

Part three: THE FEEDBACK LOOP

Posted by Marty in Assorted. Tagged: , , , , .

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“But what mechanism connected trauma exposure to low cortisol to future PTSD? We began a series of studies to answer this question. Significantly, we found that Vietnam veterans with PTSD had a greater number of glucocorticoid receptors. These are proteins to which cortisol binds to exert its diverse influences. That suggested a greater sensitivity to cortisol: a small increase in the hormone’s concentration would precipitate a disproportionate physiological reaction. But it wasn’t until we looked more closely at the molecular underpinnings of cortisol functioning—in part by examining epigenetics—that we understood how exposure to trauma might reset the cortisol feedback loop.

In the 1990s scientists were realizing that the output of our genes is sensitive to factors not written directly into our genetic code. Genes provide the templates for producing proteins. But much like cakes baked using the same ingredients may turn out differently depending on variations in the oven’s temperature, how much of those proteins gets produced, or “expressed,” depends on the environment. The discovery gave rise to epigenetics, the study of what influences gene expression and how. It proved crucial to understanding both the neurobiology of PTSD and the intergenerational effects of trauma.

Epigeneticists explore the switches that turn gene expression on and off. One such mechanism, called methylation, involves a methyl group—a methane molecule that is missing one of its four hydrogen atoms, leaving a chemical bond free to attach to another atom or molecule. Methylation is a process by which, in the presence of specific enzymes, methyl groups attach to key sites on a strand of DNA or within the complex of DNA and proteins known as chromatin. By occupying these sites like roadblocks on a highway, methyl groups can alter transcription, a basic step in gene expression where a piece of RNA is made from a DNA template. Increased methylation generally impedes RNA transcription, whereas less methylation enhances transcription. These changes are enduring in that they survive normal cell division and require specific enzymes for their removal.

In 2015 our group became one of the first to pinpoint epigenetic changes on stress-related genes of veterans with PTSD. These alterations partially explained why trauma’s effects were so persistent, lasting for decades. Specifically we observed reduced methylation in an important region of NR3C1, a gene that encodes the glucocorticoid receptor, likely increasing the sensitivity of these receptors.

This epigenetic modification suggests a potential explanation for how trauma might reset cortisol levels. The body regulates the stress response through a complicated feedback mechanism. A rise in cortisol levels will prompt the body to produce less of the hormone, which may drive up the numbers and responsiveness of glucocorticoid receptors. Given the epigenetic and other changes occurring with sustained responses to trauma, the feedback loop might become recalibrated. In people who have already endured trauma, their stress systems might be sensitized and their cortisol levels diminished—increasing their adrenaline response to further trauma and leading to PTSD.”

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16 Jun

Part two: Low Cortisol levels linked to PTSD

Posted by Marty in Assorted. Tagged: , , , , , .

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This is groundbreaking. Low cortisol levels have never been linked to PTSD before. This explains why we behave as we do.

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“A shape was emerging that connected childhood adversity with low cortisol and the possibility of future PTSD.

So my team of five people landed in Cleveland, along with a centrifuge and other equipment. We stayed in my parents’ home, walking door to door to interview people by day and returning to test blood and urine samples in the evening. When the results came in, they were clear: half the Holocaust survivors had PTSD, and those with PTSD had low cortisol. There was no question about it—even if the traumatic experience was long ago, PTSD went hand in hand with low cortisol.

But why? And which came first? An important clue came from a 1984 review by Allan Munck and other researchers at the Geisel School of Medicine at Dartmouth. They noted that among stress hormones, cortisol played a special, regulatory role. High levels of stress hormones, if sustained for a long time, harm the body in multiple ways—weakening the immune system and increasing susceptibility to problems such as hypertension. But in a context of acute trauma, cortisol may paradoxically also have a protective effect. It shuts down the release of stress hormones—including itself—reducing the potential damage to organs and the brain. Such a trauma-induced feedback loop could conceivably reset the cortisol “thermostat” to a lower level.

I picked up another piece of the puzzle and placed it. In the early 1990s we’d shown that Vietnam veterans were more likely to develop PTSD if they’d been abused as children. Slowly a shape was emerging that connected intense childhood adversity—a period of “freeze” because a child usually cannot fight or flee—with low cortisol and the possibility of future PTSD. We studied people who’d been raped or who’d been in auto accidents when they came into emergency rooms, finding that those with lower cortisol levels were more likely to develop PTSD after the attack or accident.

Could low cortisol levels have been present before the event that brought them into the emergency room? I wondered. If someone with low cortisol was subjected to a traumatic experience, we reasoned, the cortisol levels in their bodies might be too low to tamp down the stress reaction. Adrenaline levels might then shoot way up, searing the memory of the new trauma into the brain—from where it might later surface as flashbacks or nightmares. Perhaps low cortisol marked a vulnerability to developing PTSD.

The study of Holocaust offspring supported this conjecture. Children of Holocaust survivors with PTSD tended to have low cortisol even if they did not have their own PTSD. As we’d suspected, low cortisol seemed related to vulnerability to PTSD.”

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16 Jun

Part One: IN THE FAMILY TREE Parents’ adverse experiences leave biological traces in children By Rachel Yehuda

Posted by Marty in Assorted. Tagged: , , , , , , .

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FIGHT, FLIGHT—OR FREEZE

“What did it all mean? Unraveling the tangle of trauma, cortisol and PTSD has occupied me and many other researchers for the decades since. In the classic fight-or-flight response, identified in the 1920s, a threatening encounter triggers the release of stress hormones such as adrenaline and cortisol. The hormones prompt a cascade of changes, such as quickening the pulse and sharpening the senses to enable the threatened person or animal to focus on and react to the immediate danger. These acute effects were believed to dissipate once the danger receded.

In 1980, however, psychiatrists and other advocates for Vietnam War veterans won a prolonged struggle to get post-traumatic stress included in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). It was the first official recognition that trauma could have long-lasting effects. But the diagnosis was controversial. Many psychologists believed that its inclusion in the DSM-III had been politically, rather than scientifically, driven—in part because there were no scientific explanations for how a threat could continue to influence the body long after it was removed.

Complicating matters, studies of Vietnam veterans were generating perplexing results. In the mid-1980s neuroscientists John Mason, Earl Giller and Thomas Kosten of Yale University reported that veterans with PTSD had high levels of adrenaline but lower levels of cortisol than patients with other psychiatric diagnoses. Because stress usually causes stress hormones, including cortisol, to rise, many researchers, including myself, were skeptical of these observations. When I joined the Yale laboratory as a postdoctoral fellow a year later, I studied a different group of veterans using other methods for measuring cortisol. To my astonishment, I replicated the finding.

I still couldn’t believe that the low cortisol levels had anything to do with trauma. Surely the Holocaust was as terrible as the Vietnam War, I reasoned—and growing up as a rabbi’s daughter in a community full of Holocaust survivors, many of them my friends’ parents, I’d noticed nothing out of the ordinary about them. I was sure that they didn’t have either PTSD or low cortisol, I told my mentor, Giller. “That’s a testable hypothesis,” he responded. “Why don’t you study that, instead of conjecturing?”

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17 Mar

For those habituated to high levels of internal stress since early childhood, it is the absence of stress that creates unease, evoking boredom and a sense of meaninglessness

Posted by Marty in Assorted. Tagged: , , , , , , , , , , , , , , , .

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“Adult Children of Alcoholics”: The Bridge in the Problem:

“We were dependent personalities, terrified of abandonment, willing to do almost anything to hold on to a relationship in order to not to be abandoned emotionally.

Yet we kept choosing insecure relationships because they matched our childhood relationship with alcoholic or dysfunctional parents.”

These two sentences seem disjointed. We are terrified of something, yet we seek it out.

Perhaps it is our Addiction to Excitement that creates the bridge between those two lines.

You could almost cross out the word “Yet” and replace it with “And so.”

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My two cents: I was terrified of abandonment and maybe with good reason, now my family has abandoned me.

What rings true is the drama in life I have experienced.

Now, I am searching out my connection to this behavior.

At 68, I am getting closer to being happier, less controlled by trauma and fear.

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