Posts tagged stress

July 18, 2012

Sleep deprivation in the first few hours after exposure to a significantly stressful threat actually reduces the risk of Post-Traumatic Stress Disorder (PTSD), according to a study by researchers from Ben-Gurion University of the Negev (BGU) and Tel Aviv University.

The new study was published in the international scientific journal, Neuropsychopharmacology. It revealed in a series of experiments that sleep deprivation of approximately six hours immediately after exposure to a traumatic event reduces the development of post trauma-like behavioral responses. As a result, sleep deprivation the first hours after stress exposure might represent a simple, yet effective, intervention for PTSD.

The research was conducted by Prof. Hagit Cohen, director of the Anxiety and Stress Research Unit at BGU’s Faculty of Health Sciences, in collaboration with Prof. Joseph Zohar of Tel Aviv University.

Approximately 20 percent of people exposed to a severe traumatic event, such as a car or work accident, terrorist attack or war, cannot normally carry on their lives. These people retain the memory of the event for many years. It causes considerable difficulties in the person’s functioning in daily life and, in extreme cases, may render the individual completely dysfunctional.

"Often those close to someone exposed to a traumatic event, including medical teams, seek to relieve the distress and assume that it would be best if they could rest and "sleep on it," says Prof. Cohen. "Since memory is a significant component in the development of post-traumatic symptoms, we decided to examine the various effects of sleep deprivation immediately after exposure to trauma."

In the experiments, rats that underwent sleep deprivation after exposure to trauma (predator scent stress exposure), later did not exhibit behavior indicating memory of the event, while a control group of rats that was allowed to sleep after the stress exposure did remember, as shown by their post trauma-like behavior.

"As is the case for human populations exposed to severe stress, 15 to 20 percent of the animals develop long-term disruptions in their behavior," says Cohen. "Our research method for this study is, we believe, a breakthrough in biomedical research."

A pilot study in humans is currently being planned. The studies were funded by a Israel Academy of Science and Humanities grant and the Israel Ministry of Health.

Provided by American Associates, Ben-Gurion University of the Negev

Source: medicalxpress.com

June 27, 2012 by Bob Yirka

(Medical Xpress) — Research teams from the US and Korea have together been studying depression and other mood disorders and have found that chronic stress can block a gene whose job it is to maintain healthy neuron connections in the brain, which in turn can lead to mental ailments. In lab experiments they have found that rats show lowered levels of neuritin gene activity when driven to depression, and that rats with depression tended to do better when given treatment that boosted neuritin activity, suggesting that another means of treating people with mood disorders might be on the horizon. The team has published a paper describing their experiments and results in the Proceedings of the National Academy of Sciences.

Prior research has shown that people who suffer from chronic depression tend to lose plasticity, or the ability to organize new information in their brains, specifically in the hippocampus, leading to a degree of atrophy, a condition that makes it difficult for such people to recover from their disorder even when given drugs to help treat the symptoms. Until now however, most drugs that are used to treat mood disorders work by blocking the re-absorption of the brain chemical serotonin. In this new research, the team looked at the role of neuritin gene activity instead.

In lab experiments they first caused rats to become depressed by exposing them to a constantly stressful environment, e.g. putting them alone in a sterile environment, limiting food and alternating their night/day cycle. After about three weeks the rats became lethargic and unresponsive to normal stimuli. Once that was done, they tested them for the degree of neuritin gene activity, and found that such levels had dropped in all of them. They then treated some of the rates with standard mood stabilizers which helped reduced symptoms as it has in previous research. But then, they treated some of the other rats by infecting them with a virus that causes an increase in neuritin gene activity and found doing so helped the rats just as much as standard therapies and also served to protect their brains from atrophy.

In another experiment the team forced lowered neuritin gene activity in a group of rats but didn’t subject them to stress and found the rats became just as depressed as had those in the first experiment.

The team notes that while their results look very promising on paper, assuming the same results would occur with people is premature as there are differences in biology. Their results do however support the notion that stress itself contributes to mood disorders, which is information people can use to help them live more mentally healthy lives right now.

More information: Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress, PNAS, Published online before print June 25, 2012, doi: 10.1073/pnas.1201191109

Source: medicalxpress.com

June 27th, 2012

Researchers from the Huck Institutes’ Center for Cellular Dynamics, led by Center director Melissa Rolls, have found that a neuroprotective pathway initiated in response to injured or stressed neural axons serves to stabilize and protect the nerve cell against further degeneration.

Neurons, or nerve cells, typically have a single axon that transmits signals to other neurons or to output cells such as muscle tissue, and as these axons extend for long distances within the cell, they are thus at risk for injury.

Furthermore, if an axon is damaged, its parent neuron can no longer function; and since many animals develop only one set of neurons, those neurons will mount major responses to axon injury.

“Neurons are quite remarkable cells,” says Dr. Rolls. “Most of them need to survive and function for your entire lifetime. Maybe then it shouldn’t be a surprise that they do not give up easily when damaged or stressed, but it is amazing to be able to watch them fight back and stabilize themselves.”

Neurons expressing a toxic form of spinocerebellar ataxia type 3 (SCA3) with protective pathway enabled (left) and blocked (right). Image adapted from Penn State press release image with credit to Melissa Rolls. Click for larger view and original image from Penn State.

Dissecting Drosophila

Dr. Rolls and her team set out to understand these cellular responses to axon injury by observing the effects of severing fruit fly axons with a laser.

What they found was that the neurons responded to the injury by increasing production of microtubules — cytoskeletal components responsible for maintaining cell structure and providing platforms for intracellular transport — in order to stabilize the neural dendrites, which are the branched structures responsible for transmitting signals to the nerve cell body.

In addition to acute injury response, the team also investigated neurons’ response to long-term axon stress — and found similar results.

Accumulation of misfolded proteins or protein aggregates — responsible for neurodegenerative diseases such as Huntington’s disease and spinocerebellar ataxia — induced the same type of cytoskeletal changes as acute axon injury.

Dr. Rolls elaborates: “The assays that we use are all in vivo, so we can literally watch what the neurons do in different scenarios, including cutting of their axon. Being able to observe the cellular responses gave us some ideas we would not have come up with otherwise. For example, it is not intuitive that expressing a protein that causes degeneration would trigger the cell to turn on a pathway that delays degeneration.”

The neuroprotective pathway

The video below shows the difference in microtubule dynamics between cells expressing a non-toxic form of the huntingtin protein (left) and cells expressing a disease-causing form (right).

[Video: Axon injury and stress trigger a microtubule-based neuroprotective pathway]
Credit: Melissa Rolls, Director, Center for Cellular Dynamics

Conclusions and implications

Based on their observations, the authors suggest that this pathway represents an endogenous neuroprotective response to axon stress — and could potentially be developed into a diagnostic tool for the detection of early stages of neurodegenerative disease, or even utilized in novel therapies for such illnesses.

“We don’t yet know if all types of neurodegenerative disease trigger this type of stabilization pathway; but if there are some diseases in which it is off, then it may be beneficial to try to turn it on to help the neurons resist degeneration,” says Dr. Rolls.

The results of the study have been published in Proceedings of the National Academy of Sciences.

Source: Neuroscience News

June 25, 2012 By Rick Nauert

A new study involving children with Williams syndrome (WS) suggests that improved regulation of oxytocin and vasopressin may someday improve care for autism, anxiety, post-traumatic stress disorder and WS.

WS results when certain genes are absent because of a faulty recombination event during the development of sperm or egg cells. Virtually everyone with WS has exactly the same set of genes missing (25 to 28 genes are missing from one of two copies of chromosome 7).

“The genetic deficiencies allow researchers to examine the genetic and neuronal basis of social behavior,” said Ursula Bellugi, Ph.D., a co-author on the paper.

“This study provides us with crucial information about genes and brain regions involved in the control of oxytocin and vasopressin, hormones that may play important roles in other disorders.”

In the study, scientists at the Salk Institute for Biological Studies and the University of Utah, found that people with WS flushed with the hormones oxytocin and arginine vasopressin (AVP) when exposed to emotional triggers.

Children with WS love people, despite being challenged with numerous health problems. WS kids are extremely gregarious, irresistibly drawn to strangers, and insist on making eye contact.

They have an affinity for music. But they also experience heightened anxiety, have an average IQ of 60, experience severe spatial-visual problems, and suffer from cardiovascular and other health issues.

Yet despite their desire to befriend people, WS kids have difficulty creating and maintaining social relationships — an issue that obviously affects many people without WS.

In the new study, led by Julie R. Korenberg, M.D., 21 participants, 13 who have WS and a control group of eight people without the disorder were evaluated at the Cedars-Sinai Medical Center in Los Angeles. Because music is a known strong emotional stimulus, the researchers asked participants to listen to music.

Before the music was played, the participants’ blood was drawn to determine a baseline level for oxytocin. Remarkably, those with WS had three times as much of the hormone as those without the syndrome.

Blood also was drawn at regular intervals while the music played and was analyzed afterward to check for real-time, rapid changes in the levels of oxytocin and AVP.

While other studies have examined how oxytocin affects emotion when artificially introduced into people, such as through nasal sprays, this is one of the first significant studies to measure naturally occurring changes in oxytocin levels in rapid, real time as people undergo an emotional response.

Although the WS participants displayed little outward response to the music, an analyses of blood samples showed that the oxytocin levels, and to a lesser degree AVP, had increased sharply while they had listened to the music.

In contrast, among those without WS, both the oxytocin and AVP levels remained largely unchanged as they listened to music.

Korenberg believes the blood analyses strongly indicate that oxytocin and AVP are not regulated correctly in people with WS, and that the behavioral characteristics unique to people with WS are related to this problem. “This shows that oxytocin quite likely is very involved in emotional response,” she said.

In addition to listening to music, study participants already had taken three social behavior tests that evaluate willingness to approach and speak to strangers, emotional states, and various areas of adaptive and problem behavior.

Those test results suggest that increased levels of oxytocin are linked to both increased desire to seek social interaction and decreased ability to process social cues, a double-edged message that may be very useful at times, for example, during courtship, but damaging at others, as in WS.

“The association between abnormal levels of oxytocin and AVP and altered social behaviors found in people with Williams Syndrome points to surprising, entirely unsuspected deleted genes involved in regulation of these hormones and human sociability,” Korenberg said.

“It also suggests that the simple characterization of oxytocin as ‘the love hormone’ may be an overreach. The data paint a far more complicated picture.”

Overall, the researchers say, their findings paint a hopeful picture, and the study holds promise for speeding progress in treating WS, and perhaps autism and anxiety through regulation of these key players in human brain and emotion, oxytocin and vasopressin.

Source: PsychCentral

June 12, 2012

Financial loss can lead to irrational behavior. Now, research by Weizmann Institute scientists reveals that the effects of loss go even deeper: Loss can compromise our early perception and interfere with our grasp of the true situation. The findings, which recently appeared in the Journal of Neuroscience, may also have implications for our understanding of the neurological mechanisms underlying post-traumatic stress disorder.

The experiment was conducted by Dr. Rony Paz and research student Offir Laufer of the Neurobiology Department. Subjects underwent a learning process based on classic conditioning and involving money. They were asked to listen to a series of tones composed of three different notes. After hearing one note, they were told they had earned a certain sum; after a second note, they were informed that they had lost some of their money; and a third note was followed by the message that their bankroll would remain the same. According to the findings, when a note was tied to gain, or at least to no loss, the subjects improved over time in a learned task – distinguishing that note from other, similar notes. But when they heard the “lose money” note, they actually got worse at telling one from the other.

Functional MRI (fMRI) scans of the brain areas involved in the learning process revealed an emotional aspect: The amygdala, which is tied to emotions and reward, was strongly involved. The researchers also noted activity in another area in the front of the brain, which functions to moderate the emotional response. Subjects who exhibited stronger activity in this area showed less of a drop in their abilities to distinguish between tones.

Paz: “The evolutionary origins of that blurring of our ability to discriminate are positive: If the best response to the growl of a lion is to run quickly, it would be counterproductive to distinguish between different pitches of growl. Any similar sound should make us flee without thinking. Unfortunately, that same blurring mechanism can be activated today in stress-inducing situations that are not life-threatening – like losing money – and this can harm us.”

That harm may even be quite serious: For instance, it may be involved in post-traumatic stress disorder. If sufferers are unable to distinguish between a stimulus that should cause a panic response and similar, but non-threatening, stimuli, they may experience strong emotional reactions in inappropriate situations.

This perceptional blurring may even expand over time to encompass a larger range of stimuli. Paz intends to investigate this possibility in future research.

Provided by Weizmann Institute of Science

Source: medicalxpress.com

June 6, 2012 by Chris Barncard

Stress may affect brain development in children — altering growth of a specific piece of the brain and abilities associated with it — according to researchers at the University of Wisconsin–Madison.

"There has been a lot of work in animals linking both acute and chronic stress to changes in a part of the brain called the prefrontal cortex, which is involved in complex cognitive abilities like holding on to important information for quick recall and use,” says Jamie Hanson, a UW–Madison psychology graduate student. “We have now found similar associations in humans, and found that more exposure to stress is related to more issues with certain kinds of cognitive processes.”

Children who had experienced more intense and lasting stressful events in their lives posted lower scores on tests of what the researchers refer to as spatial working memory. They had more trouble navigating tests of short-term memory such as finding a token in a series of boxes, according to the study, which will be published in the June 6 issue of the Journal of Neuroscience.

Brain scans revealed that the anterior cingulate, a portion of the prefrontal cortex believed to play key roles in spatial working memory, takes up less space in children with greater exposure to very stressful situations.

"These are subtle differences, but differences related to important cognitive abilities" Hanson says.

But they maybe not irreversible differences.

"We’re not trying to argue that stress permanently scars your brain. We don’t know if and how it is that stress affects the brain," Hanson says. "We only have a snapshot — one MRI scan of each subject — and at this point we don’t understand whether this is just a delay in development or a lasting difference. It could be that, because the brains is very plastic, very able to change, that children who have experienced a great deal of stress catch up in these areas."

The researchers determined stress levels through interviews with children ages 9 to 14 and their parents. The research team, which included UW–Madison psychology professors Richard Davidson and Seth Pollak and their labs, collected expansive biographies of stressful events from slight to severe.

"Instead of focusing in on one specific type of stress, we tried to look at a range of stressors," Hanson says. "We wanted to know as much as we could, and then use all this information to later to get an idea of how challenging and chronic and intense each experience was for the child."

Interestingly, there was little correlation between cumulative life stress and age. That is, children who had several more years of life in which to experience stressful episodes were no more likely than their younger peers to have accumulated a length stress resume. Puberty, on the other hand, typically went hand-in-hand with heavier doses of stress.

The researchers, whose work was funded by the National Institutes of Health, also took note of changes in brain tissue known as white matter and gray matter. In the important brain areas that varied in volume with stress, the white and gray matter volumes were lower in tandem.

White matter, Hanson explained, is like the long-distance wiring of the brain. It connects separated parts of the brain so that they can share information. Gray matter “does the math,” Hanson says. “It takes care of the processing, using the information that gets shared along the white matter connections.”

Gray matter early in development appears to enable flexibility; children can play and excel at many different activities. But as kids age and specialize, gray matter thins. It begins to be “pruned” after puberty, while the amount of white matter grows into adulthood.

"For both gray and white matter, we actually see smaller volumes associated with high stress," Hanson says. "Those kinds of effects across different kinds of tissue, those are the things we would like to study over longer periods of time. Understanding how these areas change can give you a better picture of whether this is just a delay in development or more lasting."

More study could also show the researchers how to help children who have experienced an inordinate amount of stress.

"There are groups around the country doing working memory interventions to try to train or retrain people on this particular cognitive ability and improve performance," Hanson says. "Understanding if and how stress affects these processes could help us know whether there may be similar interventions that could aid children living in stressful conditions, and how this may affect the brain.”

Provided by University of Wisconsin-Madison

Source: medicalxpress.com

ScienceDaily (Apr. 2, 2012) — Why do some persons succumb to post-traumatic stress disorder (PTSD) while others who suffered the same ordeal do not? A new UCLA study sheds light on the answer.

UCLA scientists have linked two genes involved in serotonin production to a higher risk of developing PTSD. Published in the April 3 online edition of the Journal of Affective Disorders, the findings suggest that susceptibility to PTSD is inherited, pointing to new ways of screening for and treating the disorder.

"People can develop post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster," explained lead author Dr. Armen Goenjian, a research professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. "If confirmed, our findings could eventually lead to new ways to screen people at risk for PTSD and target specific medicines for preventing and treating the disorder."

PTSD can arise following child abuse, terrorist attacks, sexual or physical assault, major accidents, natural disasters or exposure to war or combat. Symptoms include flashbacks, feeling emotionally numb or hyper-alert to danger, and avoiding situations that remind one of the original trauma.

Goenjian and his colleagues extracted the DNA of 200 adults from several generations of 12 extended families who suffered PTSD symptoms after surviving the devastating 1988 earthquake in Armenia.

In studying the families’ genes, the researchers found that persons who possessed specific variants of two genes were more likely to develop PTSD symptoms. Called TPH1 and TPH2, these genes control the production of serotonin, a brain chemical that regulates mood, sleep and alertness — all of which are disrupted in PTSD.

"We suspect that the gene variants produce less serotonin, predisposing these family members to PTSD after exposure to violence or disaster," said Goenjian. "Our next step will be to try and replicate the findings in a larger, more heterogeneous population."

Affecting about 7 percent of Americans, PTSD has become a pressing health issue for a large percentage of war veterans returning from Iraq and Afghanistan. The UCLA team’s discovery could be used to help screen persons who may be at risk for developing PTSD.

"A diagnostic tool based upon TPH1 and TPH2 could enable military leaders to identify soldiers who are at higher risk of developing PTSD, and reassign their combat duties accordingly," observed Goenjian. "Our findings may also help scientists uncover alternative treatments for the disorder, such as gene therapy or new drugs that regulate the chemicals responsible for PTSD symptoms."

According to Goenjian, pinpointing genes connected with PTSD symptoms will help neuroscientists classify the disorder based on brain biology instead of clinical observation. Psychiatrists currently rely on a trial and error approach to identify the best medication for controlling an individual patient’s symptoms.

Serotonin is the target of the popular antidepressants known as SSRIs, or selective serotonin re-uptake inhibitors, which prolong the effect of serotonin in the brain by slowing its absorption by brain cells. More physicians are prescribing SSRIs to treat psychiatric disease beyond depression, including PTSD and obsessive compulsive disorder.

Source: Science Daily