Posts tagged stress
Posts tagged stress
Overworked and stressed out? Look on the bright side. Some stress is good for you.
“You always think about stress as a really bad thing, but it’s not,” said Daniela Kaufer, associate professor of integrative biology at the University of California, Berkeley. “Some amounts of stress are good to push you just to the level of optimal alertness, behavioral and cognitive performance.”
New research by Kaufer and UC Berkeley post-doctoral fellow Elizabeth Kirby has uncovered exactly how acute stress – short-lived, not chronic – primes the brain for improved performance.
In studies on rats, they found that significant, but brief stressful events caused stem cells in their brains to proliferate into new nerve cells that, when mature two weeks later, improved the rats’ mental performance.
“I think intermittent stressful events are probably what keeps the brain more alert, and you perform better when you are alert,” she said.
Kaufer, Kirby and their colleagues in UC Berkeley’s Helen Wills Neuroscience Institute describe their results in a paper published April 16 in the new open access online journal eLife.
The UC Berkeley researchers’ findings, “in general, reinforce the notion that stress hormones help an animal adapt – after all, remembering the place where something stressful happened is beneficial to deal with future situations in the same place,” said Bruce McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at The Rockefeller University, who was not involved in the study.
Kaufer is especially interested in how both acute and chronic stress affect memory, and since the brain’s hippocampus is critical to memory, she and her colleagues focused on the effects of stress on neural stem cells in the hippocampus of the adult rat brain. Neural stem cells are a sort of generic or progenitor brain cell that, depending on chemical triggers, can mature into neurons, astrocytes or other cells in the brain. The dentate gyrus of the hippocampus is one of only two areas in the brain that generate new brain cells in adults, and is highly sensitive to glucocorticoid stress hormones, Kaufer said.
Much research has demonstrated that chronic stress elevates levels of glucocorticoid stress hormones, which suppresses the production of new neurons in the hippocampus, impairing memory. This is in addition to the effect that chronically elevated levels of stress hormones have on the entire body, such as increasing the risk of chronic obesity, heart disease and depression.
Less is known about the effects of acute stress, Kaufer said, and studies have been conflicting.
To clear up the confusion, Kirby subjected rats to what, to them, is acute but short-lived stress – immobilization in their cages for a few hours. This led to stress hormone (corticosterone) levels as high as those from chronic stress, though for only a few hours. The stress doubled the proliferation of new brain cells in the hippocampus, specifically in the dorsal dentate gyrus.
Kirby discovered that the stressed rats performed better on a memory test two weeks after the stressful event, but not two days after the event. Using special cell labeling techniques, the researchers established that the new nerve cells triggered by the acute stress were the same ones involved in learning new tasks two weeks later.
“In terms of survival, the nerve cell proliferation doesn’t help you immediately after the stress, because it takes time for the cells to become mature, functioning neurons,” Kaufer said. “But in the natural environment, where acute stress happens on a regular basis, it will keep the animal more alert, more attuned to the environment and to what actually is a threat or not a threat.”
They also found that nerve cell proliferation after acute stress was triggered by the release of a protein, fibroblast growth factor 2 (FGF2), by astrocytes — brain cells formerly thought of as support cells, but that now appear to play a more critical role in regulating neurons.
“The FGF2 involvement is interesting, because FGF2 deficiency is associated with depressive-like behaviors in animals and is linked to depression in humans,” McEwen said.
Kaufer noted that exposure to acute, intense stress can sometimes be harmful, leading, for example, to post-traumatic stress disorder. Further research could help to identify the factors that determine whether a response to stress is good or bad.
“I think the ultimate message is an optimistic one,” she concluded. “Stress can be something that makes you better, but it is a question of how much, how long and how you interpret or perceive it.”
Fear of public speaking tops death and spiders as the nation’s number one phobia. But new research shows that learning to rethink the way we view our shaky hands, pounding heart, and sweaty palms can help people perform better both mentally and physically.
Before a stressful speaking task, simply encouraging people to reframe the meaning of these signs of stress as natural and helpful was a surprisingly effective way of handling stage fright, found the study to be published online April 8 in Clinical Psychological Science.
“The problem is that we think all stress is bad,” explains Jeremy Jamieson, the lead author on the study and an assistant professor of psychology at the University of Rochester. “We see headlines about ‘Killer Stress’ and talk about being ‘stressed out.’” Before speaking in public, people often interpret stress sensations, like butterflies in the stomach, as a warning that something bad is about to happen, he says.
“But those feelings just mean that our body is preparing to address a demanding situation,” explains Jamieson. “The body is marshaling resources, pumping more blood to our major muscle groups and delivering more oxygen to our brains.” Our body’s reaction to social stress is the same flight or fight response we produce when confronting physical danger. These physiological responses help us perform, whether we’re facing a bear in the forest or a critical audience.
For many people, especially those suffering from social anxiety disorder, the natural uneasiness experienced before giving a speech can quickly tip over into panic. “If we think we can’t cope with stress, we will experience threat. When threatened, the body enacts changes to concentrate blood in the core and restricts flow to the arms, legs, and brain,” he explains. So, “cold feet” is a real physiological response to threat, not just a colorful expression.
“Lots of current advice for anxious people focuses on learning to ‘relax,’—you know, deep, even breathing and similar tips,” says Jamieson. Such calming techniques, write the authors, may be helpful in situations that do not require peak performance. But when gearing up for a high-stakes exam, a job interview, or, yes, a speaking engagement, reframing how we think about stress may be a better strategy.
Then how can people reap the benefits of being stressed without being overwhelmed by dread? To answer that question, Jamieson and co-authors Matthew Nock, of Harvard University and Wendy Berry Mendes of the University of California in San Francisco, turned to the Trier Social Stress Test. Developed in 1993 by Clemens Kirschbaum and colleagues, this experiment relies on fear of public speaking and has become one of the most reliable laboratory methods for eliciting threat responses.
In the study, 69 adults were asked to give a five-minute talk about their strengths and weaknesses with only three minutes to prepare. Roughly half of the participants had a history of social anxiety and all participants were randomly assigned to two groups. The first group was presented information about the advantages of the body’s stress response and encouraged to “reinterpret your bodily signals during the upcoming public speaking task as beneficial.” That group also was asked to read summaries of three psychology studies that showed the benefits of stress. The second group received no information about reframing stress.
Participants delivered their speech to two judges. On purpose, the judges provided negative nonverbal feedback throughout the entire five-minute presentations, shaking their heads in disapproval, tapping on their clipboards, and staring stone-faced ahead. If study subjects ran out of things to say, the judges insisted that they continue speaking for the full five minutes. Following the speech, participants were asked to count backwards for five minutes in steps of seven beginning with the number 996. The evaluators again provided negative feedback throughout and insisted that participants start over if they made any mistakes.
Confronted with scowling judges, participants who received no stress preparation experienced a threat response, as captured by cardiovascular measures. But the group that was prepped about the benefits of stress weathered the trial better. That group reported feeling that they had more resources to cope with the public speaking task and, perhaps more tellingly, their physiological responses confirmed those perceptions. The prepped group pumped more blood through the body per minute compared to the group that did not receive instruction.
Surprisingly, this study also found that individuals who suffer from social anxiety disorder actually experienced no greater increase in physiological arousal while under scrutiny than their non-anxious counterparts, despite reporting more intense feelings of apprehension. This disconnect, argue the authors, supports the theory that our experience of acute or short-term stress is shaped by how we interpret physical cues. “We construct our own emotions,” says Jamieson.
Exposure of the developing foetus to excessive levels of stress hormones in the womb can cause mood disorders in later life and now, for the first time, researchers have found a mechanism that may underpin this process, according to research presented today (Sunday) at the British Neuroscience Association Festival of Neuroscience (BNA2013) in London.
The concept of foetal programming of adult disease, whereby the environment experienced in the womb can have profound long-lasting consequences on health and risk of disease in later life, is well known; however, the process that drives this is unclear. Professor Megan Holmes, a neuroendocrinologist from the University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science in Scotland (UK), will say: “During our research we have identified the enzyme 11ß-HSD2 which we believe plays a key role in the process of foetal programming.”
Adverse environments experienced while in the womb, such as in cases of stress, bereavement or abuse, will increase levels of glucocorticoids in the mother, which may harm the growing baby. Glucocorticoids are naturally produced hormones and they are also known as stress hormones because of their role in the stress response.
“The stress hormone cortisol may be a key factor in programming the foetus, baby or child to be at risk of disease in later life. Cortisol causes reduced growth and modifies the timing of tissue development as well as having long lasting effects on gene expression,” she will say.
Prof Holmes will describe how her research has identified an enzyme called 11ß-HSD2 (11beta-hydroxysteroid dehydrogenase type 2) that breaks down the stress hormone cortisol to an inactive form, before it can cause any harm to the developing foetus. The enzyme 11ß-HSD2 is present in the placenta and the developing foetal brain where it is thought to act as a shield to protect against the harmful actions of cortisol.
Prof Holmes and her colleagues developed genetically modified mice that lacked 11ß-HSD2 in order to determine the role of the enzyme in the placenta and foetal brain. “In mice lacking the enzyme 11ß-HSD2, foetuses were exposed to high levels of stress hormones and, as a consequence, these mice exhibited reduced foetal growth and went on to show programmed mood disorders in later life. We also found that the placentas from these mice were smaller and did not transport nutrients efficiently across to the developing foetus. This too could contribute to the harmful consequences of increased stress hormone exposure on the foetus and suggests that the placental 11ß-HSD2 shield is the most important barrier.
“However, preliminary new data show that with the loss of the 11ß-HSD2 protective barrier solely in the brain, programming of the developing foetus still occurs, and, therefore, this raises questions about how dominant a role is played by the placental 11ß-HSD2 barrier. This research is currently ongoing and we cannot draw any firm conclusions yet.
“Determining the exact molecular and cellular mechanisms that drive foetal programming will help us identify potential therapeutic targets that can be used to reverse the deleterious consequences on mood disorders. In the future, we hope to explore the potential of these targets in studies in humans,” she will say.
Prof Holmes hopes that her research will make healthcare workers more aware of the fact that children exposed to an adverse environment, be it abuse, malnutrition, or bereavement, are at an increased risk of mood disorders in later life and the children should be carefully monitored and supported to prevent this from happening.
In addition, the potential effects of excessive levels of stress hormones on the developing foetus are also of relevance to individuals involved in antenatal care. Within the past 20 years, the majority of women at risk of premature delivery have been given synthetic glucocorticoids to accelerate foetal lung development to allow the premature babies to survive early birth.
“While this glucocorticoid treatment is essential, the dose, number of treatments and the drug used, have to be carefully monitored to ensure that the minimum effective therapy is used, as it may set the stage for effects later in the child’s life,” Prof Holmes will say.
Puberty is another sensitive time of development and stress experienced at this time can also be involved in programming adult mood disorders. Prof Holmes and her colleagues have found evidence from imaging studies in rats that stress in early teenage years could affect mood and emotional behaviour via changes in the brain’s neural networks associated with emotional processing.
The researchers used fMRI (Functional Magnetic Resonance Imaging) to see which pathways in the brain were affected when stressed, peripubertal rats responded to a specific learned task.
Prof Holmes will say: “We showed that in stressed ‘teenage’ rats, the part of the brain region involved in emotion and fear (known as amygdala) was activated in an exaggerated fashion when compared to controls. The results from this study clearly showed that altered emotional processing occurs in the amygdala in response to stress during this crucial period of development.”
Researchers at the University of Calgary’s Hotchkiss Brain Institute have discovered that stress circuits in the brain undergo profound learning early in life. Using a number of cutting edge approaches, including optogenetics, Jaideep Bains, PhD, and colleagues have shown stress circuits are capable of self-tuning following a single stress. These findings demonstrate that the brain uses stress experience during early life to prepare and optimize for subsequent challenges.
The team was able to show the existence of unique time windows following brief stress challenges during which learning is either increased or decreased. By manipulating specific cellular pathways, they uncovered the key players responsible for learning in stress circuits in an animal model. These discoveries culminated in the publication of two back-to-back studies in the April 7 online edition of Nature Neuroscience [1, 2], one of the world’s top neuroscience journals.
“These new findings demonstrate that systems thought to be ‘hardwired’ in the brain, are in fact flexible, particularly early in life,” says Bains, a professor in the Department of Physiology and Pharmacology. “Using this information, researchers can now ask questions about the precise cellular and molecular links between early life stress and stress vulnerability or resilience later in life.”
Stress vulnerability, or increased sensitivity to stress, has been implicated in numerous health conditions including cardiovascular disease, obesity, diabetes and depression. Although these studies used animal models, similar mechanisms mediate disease progression in humans.
“Our observations provide an important foundation for designing more effective preventative and therapeutic strategies that mitigate the effects of stress and meet society’s health challenges,” he says.
Scientists have known for some time that the human brain’s ability to stay calm and focused is limited and can be overwhelmed by the constant noise and hectic, jangling demands of city living, sometimes resulting in a condition informally known as brain fatigue.
With brain fatigue, you are easily distracted, forgetful and mentally flighty — or, in other words, me.
But an innovative new study from Scotland suggests that you can ease brain fatigue simply by strolling through a leafy park.
The idea that visiting green spaces like parks or tree-filled plazas lessens stress and improves concentration is not new. Researchers have long theorized that green spaces are calming, requiring less of our so-called directed mental attention than busy, urban streets do. Instead, natural settings invoke “soft fascination,” a beguiling term for quiet contemplation, during which directed attention is barely called upon and the brain can reset those overstretched resources and reduce mental fatigue.
But this theory, while agreeable, has been difficult to put to the test. Previous studies have found that people who live near trees and parks have lower levels of cortisol, a stress hormone, in their saliva than those who live primarily amid concrete, and that children with attention deficits tend to concentrate and perform better on cognitive tests after walking through parks or arboretums. More directly, scientists have brought volunteers into a lab, attached electrodes to their heads and shown them photographs of natural or urban scenes, and found that the brain wave readouts show that the volunteers are more calm and meditative when they view the natural scenes.
But it had not been possible to study the brains of people while they were actually outside, moving through the city and the parks. Or it wasn’t, until the recent development of a lightweight, portable version of the electroencephalogram, a technology that studies brain wave patterns.
For the new study, published this month in The British Journal of Sports Medicine, researchers at Heriot-Watt University in Edinburgh and the University of Edinburgh attached these new, portable EEGs to the scalps of 12 healthy young adults. The electrodes, hidden unobtrusively beneath an ordinary looking fabric cap, sent brain wave readings wirelessly to a laptop carried in a backpack by each volunteer.
The researchers, who had been studying the cognitive impacts of green spaces for some time, then sent each volunteer out on a short walk of about a mile and half that wound through three different sections of Edinburgh.
The first half mile or so took walkers through an older, historic shopping district, with fine, old buildings and plenty of pedestrians on the sidewalk, but only light vehicle traffic.
The walkers then moved onto a path that led through a park-like setting for another half mile.
Finally, they ended their walk strolling through a busy, commercial district, with heavy automobile traffic and concrete buildings.
The walkers had been told to move at their own speed, not to rush or dawdle. Most finished the walk in about 25 minutes.
Throughout that time, the portable EEGs on their heads continued to feed information about brain wave patterns to the laptops they carried.
Afterward, the researchers compared the read-outs, looking for wave patterns that they felt were related to measures of frustration, directed attention (which they called “engagement”), mental arousal and meditativeness or calm.
What they found confirmed the idea that green spaces lessen brain fatigue.
When the volunteers made their way through the urbanized, busy areas, particularly the heavily trafficked commercial district at the end of their walk, their brain wave patterns consistently showed that they were more aroused, attentive and frustrated than when they walked through the parkland, where brain-wave readings became more meditative.
While traveling through the park, the walkers were mentally quieter.
Which is not to say that they weren’t paying attention, said Jenny Roe, a professor in the School of the Built Environment at Heriot-Watt University, who oversaw the study. “Natural environments still engage” the brain, she said, but the attention demanded “is effortless. It’s called involuntary attention in psychology. It holds our attention while at the same time allowing scope for reflection,” and providing a palliative to the nonstop attentional demands of typical, city streets.
Of course, her study was small, more of a pilot study of the nifty new, portable EEG technology than a definitive examination of the cognitive effects of seeing green.
But even so, she said, the findings were consistent and strong and, from the viewpoint of those of us over-engaged in attention-hogging urban lives, valuable. The study suggests that, right about now, you should consider “taking a break from work,” Dr. Roe said, and “going for a walk in a green space or just sitting, or even viewing green spaces from your office window.” This is not unproductive lollygagging, Dr. Roe helpfully assured us. “It is likely to have a restorative effect and help with attention fatigue and stress recovery.”
-by Gretchen Reynolds, The New York Times
Focusing on the present rather than letting the mind drift may help to lower levels of the stress hormone cortisol, suggests new research from the Shamatha Project at the University of California, Davis.
The ability to focus mental resources on immediate experience is an aspect of mindfulness, which can be improved by meditation training.
“This is the first study to show a direct relation between resting cortisol and scores on any type of mindfulness scale,” said Tonya Jacobs, a postdoctoral researcher at the UC Davis Center for Mind and Brain and first author of a paper describing the work, published this week in the journal Health Psychology.
High levels of cortisol, a hormone produced by the adrenal gland, are associated with physical or emotional stress. Prolonged release of the hormone contributes to wide-ranging, adverse effects on a number of physiological systems.
The new findings are the latest to come from the Shamatha Project, a comprehensive long-term, control-group study of the effects of meditation training on mind and body.
Led by Clifford Saron, associate research scientist at the UC Davis Center for Mind and Brain, the Shamatha Project has drawn the attention of both scientists and Buddhist scholars including the Dalai Lama, who has endorsed the project.
In the new study, Jacobs, Saron and their colleagues used a questionnaire to measure aspects of mindfulness among a group of volunteers before and after an intensive, three-month meditation retreat. They also measured cortisol levels in the volunteers’ saliva.
During the retreat, Buddhist scholar and teacher B. Alan Wallace of the Santa Barbara Institute for Consciousness Studies trained participants in such attentional skills as mindfulness of breathing, observing mental events, and observing the nature of consciousness. Participants also practiced cultivating benevolent mental states, including loving kindness, compassion, empathic joy and equanimity.
At an individual level, there was a correlation between a high score for mindfulness and a low score in cortisol both before and after the retreat. Individuals whose mindfulness score increased after the retreat showed a decrease in cortisol.
“The more a person reported directing their cognitive resources to immediate sensory experience and the task at hand, the lower their resting cortisol,” Jacobs said.
The research did not show a direct cause and effect, Jacobs emphasized. Indeed, she noted that the effect could run either way — reduced levels of cortisol could lead to improved mindfulness, rather than the other way around. Scores on the mindfulness questionnaire increased from pre- to post-retreat, while levels of cortisol did not change overall.
According to Jacobs, training the mind to focus on immediate experience may reduce the propensity to ruminate about the past or worry about the future, thought processes that have been linked to cortisol release.
“The idea that we can train our minds in a way that fosters healthy mental habits and that these habits may be reflected in mind-body relations is not new; it’s been around for thousands of years across various cultures and ideologies,” Jacobs said. “However, this idea is just beginning to be integrated into Western medicine as objective evidence accumulates. Hopefully, studies like this one will contribute to that effort.”
Saron noted that in this study, the authors used the term “mindfulness” to refer to behaviors that are reflected in a particular mindfulness scale, which was the measure used in the study.
“The scale measured the participants’ propensity to let go of distressing thoughts and attend to different sensory domains, daily tasks, and the current contents of their minds. However, this scale may only reflect a subset of qualities that comprise the greater quality of mindfulness, as it is conceived across various contemplative traditions,” he said.
Previous studies from the Shamatha Project have shown that the meditation retreat had positive effects on visual perception, sustained attention, socio-emotional well-being, resting brain activity and on the activity of telomerase, an enzyme important for the long-term health of body cells.
All too often, stress turns addiction recovery into relapse, but years of basic brain research have provided scientists with insight that might allow them develop a medicine to help. A new study in the journal Neuron pinpoints the neural basis for stress-related relapse in rat models to an unprecedented degree. The advance could accelerate progress toward a medicine that prevents stress from undermining addiction recovery.
In the paper published March 6, researchers at Brown University and the University of Pennsylvania demonstrated specific steps in the sequence of neural events underlying stress-related drug relapse and showed that they take place within a brain region called the ventral tegmental area (VTA), which helps reinforce behaviors related to fulfilling basic needs. They also showed that a closely related neural process believed to be crucial to stress-related relapse may not be involved after all.
Moreover, this new understanding allowed the researchers to prevent relapse to drug seeking in the animal model. When they treated rats that had recovered from cocaine addiction with a chemical that blocks the “kappa opioid receptors” that stress activates in the VTA, the rats did not relapse to cocaine use under stress. Untreated rats who had also recovered from addiction did relapse after the same stress.
The chemical that helped the rats, “nor-BNI,” may be one that would someday be tried in humans, said study senior author Julie Kauer, professor of biology in Brown’s Department of Molecular Pharmacology, Physiology, and Biotechnology. By deepening scientists’ understanding of the stress-related relapse mechanism, she and her co-authors hope to identify multiple possible targets for eventual patient treatments.
“If we understand how kappa opioid receptor antagonists are interfering with the reinstatement of drug seeking we can target that process,” Kauer said. “We’re at the point of coming to understand the processes and possible therapeutic targets. Remarkably, this has worked.”
The neural crux of relapse
Exactly how stress acts in the brain to trigger relapse is a complicated sequence that is still not fully understood, but the new study focuses on and elucidates three key players at the crux of the phenomenon in the VTA: GABA-releasing neurons, dopamine-releasing neurons, and the kappa opioid receptors that affect their connections.
Fulfilling natural needs such as hunger or thirst results in a rewarding release of dopamine from the VTA’s dopamine neurons, Kauer said. Unfortunately, so does using drugs of abuse.
In normal brain function, GABA applies the brakes on the rewarding dopamine release, slowing it back to a normal level. It achieves this by forging and then strengthening the connections, called synapses, with the dopamine neuron. The strengthening process is called long-term potentiation (LTP).
In the first of their experiments, the team at Brown, including lead author Nicholas Graziane, showed that stress interrupts the LTP process, hindering GABA’s ability to slam the brakes on dopamine release.
Previous research implicated kappa opioid receptors as one of many neural entities that could have a role in stress-related relapse. Kauer, Graziane, and co-author Abigail Polter investigated that directly by blocking the receptors in some rats with a treatment of nor-BNI in the VTA and leaving others untreated. Then they subjected the rats to a standardized five-minute stress exercise. After 24 hours they looked at the cells in the VTA and found that LTP was hindered in the untreated rats but still present and underway in the rats whose receptors had been blocked with nor-BNI.
With the role of stress and the receptors in the GABA-dopamine dynamic both confirmed and then mitigated, the question remained: Could this knowledge be used to prevent relapse?
To answer that, Penn co-authors Lisa Briand and Christopher Pierce performed the experiment demonstrating that nor-BNI delivered directly to the VTA prevented stressed rats from relapsing to cocaine seeking, while untreated rats subjected to the same stress did relapse.
“Our results indicate that the kappa receptors within the VTA critically control stress-induced drug seeking in animals,” the authors wrote in Neuron.
Along the way, the team also discovered evidence that another stress-affected synapse in the VTA – one that excites dopamine release rather than inhibits it – does not play a role in the stress-related relapse as many researchers have thought. The nor-BNI treatment that prevented stress-related relapse, for example, did not affect those synapses.
Kauer emphasized that her lab’s findings of therapeutic potential are the product of more than a decade of essential basic research on the importance of how changes in synapses relate to behaviors including addiction.
“If we can figure out how not only stress, but the whole system works, then we’ll potentially have a way to tune it down in a person who needs that,” she said.
According to a new pilot study, published in IOP Publishing’s Journal of Breath Research, there are six markers in the breath that could be candidates for use as indicators of stress.
The researchers hope that findings such as these could lead to a quick, simple and non-invasive test for measuring stress; however, the study, which involved just 22 subjects, would need to be scaled-up to include more people, over a wider range of ages and in more “normal” settings, before any concrete conclusions can be made, they state.
Lead-author of the study, Professor Paul Thomas, said: “If we can measure stress objectively in a non-invasive way, then it may benefit patients and vulnerable people in long-term care who find it difficult to disclose stress responses to their carers, such as those suffering from Alzheimer’s.”
The study, undertaken by researchers at Loughborough University and Imperial College London, involved 22 young adults (10 male and 12 female) who each took part in two sessions: in the first, they were asked to sit comfortably and listen to non-stressful music; in the second, they were asked to perform a common mental arithmetic test that has been designed to induce stress.
A breath test was taken before and after each session, whilst heart-rates and blood pressures were recorded throughout. The breath samples were examined using a technique known as gas chromatography-mass spectrometry, and then statistically analysed and compared to a library of compounds.
Two compounds in the breath – 2-methyl, pentadecane and indole – increased following the stress exercise which, if confirmed, the researchers believe could form the basis of a rapid test.
A further four compounds were shown to decrease with stress, which could be due to changes in breathing patterns.
“What is clear from this study is that we were not able to discount stress. It seems sensible and prudent to test this work with more people over a range of ages in more normal settings.
“We will need to think carefully about experimental design in order to explore this potential relationship further as there are ethical issues to consider when deliberately placing volunteers under stress. Any follow up study would need to be led by experts in stress,” Professor Thomas continued.
Breath profiling has become an attractive diagnostic method for clinicians, and recently researchers have found biomarkers associated with tuberculosis, multiple cancers, pulmonary disease and asthma. It is still unclear how to best manage external factors, such as diet, environment and exercise, which can affect a person’s breath sample.
“It is possible that stress markers in the breath could mask or confound other key compounds that are used to diagnose a certain disease or condition, so it is important that these are accounted for,” said Professor Thomas.
The researcher’s initial assumptions are that stressed people breathe faster and have increased pulse rates and an elevated blood-pressure, which is likely to change their breath profile. They emphasise, however, that it is too soon to postulate the biological origins and the roles of the compounds as part of a stress-sensitive response.
When people or animals are thrust into threatening situations such as combat or attack by a predator, stress hormones are released to help prepare the organism to defend itself or to rapidly escape from danger—the so-called fight-or-flight response.
Now University of Michigan researchers have demonstrated for the first time that stress hormones are also responsible for altering the body shape of developing animals, in this case the humble tadpole, so they are better equipped to survive predator attacks.
Through a series of experiments conducted at field sites and in the laboratory, U-M researchers demonstrated that prolonged exposure to a stress hormone enabled tadpoles to increase the size of their tails, which improved their ability to avoid lethal predator attacks.
“This is the first clear demonstration that a stress hormone produced by the animal can actually cause a morphological change, a change in body shape, that improves their survival in the presence of lethal predators. It’s a survival response,” said Robert Denver, a professor of molecular, cellular and developmental biology and of ecology and evolutionary biology.
The team’s surprising findings are detailed in a paper to be published online March 5 in the journal Proceedings of the Royal Society B. First author of the paper is Jessica Middlemis Maher, a former U-M doctoral student, now at Michigan State University, who conducted the work for her dissertation.
Scientists have long known that environmental changes can prompt animals and plants to alter their morphology and physiology, as well as the timing of developmental events. For example, tadpoles can accelerate metamorphosis into frogs in response to a drying pond, a high density of predators or a lack of food.
The term “phenotypic plasticity” is used to describe modifications by animals and plants in response to a changing environment.
“There’s been a lot of interest in phenotypic plasticity among developmental biologists and evolutionary ecologists for more than 70 years, but there’s been relatively little focus on the mechanisms by which the environmental signal is translated into a functional response,” Denver said.
“We’ve known, for example, that tadpoles can change their body shape in response to predation risk. But until now, nobody knew the basic physiological mechanisms mediating that response. That’s what’s novel about this study.”
(Image: Wikimedia Commons)
Reducing fear and stress following a traumatic event could be as simple as providing a protein synthesis blocker to the brain, report a team of researchers from McLean Hospital, Harvard Medical School, McGill University, and Massachusetts General Hospital in a paper published in the March 4 issue of Proceedings of the National Academy of Sciences.
“This is an important basic neuroscience finding that has the potential to have clinical implications for the way individuals with posttraumatic stress disorder are treated,” said Vadim Bolshakov, PhD, director of the Cellular Neurobiology Laboratory at McLean Hospital. “We used a well-known behavioral paradigm that we think models PTSD, fear conditioning, to explore how fearful memories are formed. In our study, the level of fear exhibited by experimental subjects was significantly reduced as a result of decreased signal transfer between cells in the amygdala, a key brain region in fear-related behaviors.”
Influenced by the original findings of Karim Nader, PhD, professor of Psychology at McGill University, whose pioneering work showed that old memories should be un-stored in their brain after their recollection in order to last, Bolshakov’s team exposed rats to auditory stimulus that the animals learned to associate with a mildly traumatic event. After a single exposure to the training procedures, the rats exhibited fear during subsequent exposures to auditory stimuli. The researchers then provided the animals with rapamycin, a protein synthesis blocker, immediately after memory was retrieved in order to control bonding between the cells in the brain. The animals exhibited significantly less fear in response to the fear-invoking stimulus when retested the next day.
“The animals showed stereotypical signs of fear after the initial exposure to the auditory stimulus,” explained Nader, a co-author on the paper. “Following the administration of rapamycin, we show a significant decrease in fear, but not a complete elimination. We were surprised to note that activity between cells was significantly affected by postsynaptic mechanisms.”
The findings of this study, which was funded by a grant from the United States Department of Defense spearheaded by Roger Pitman, suggest that different plasticity rules within cells in the brain are recruited during the formation of the original fear memory and after fear memory was reactivated.
“Although further work at the molecular level needs to be completed, we are hopeful that this unexpected discovery is the foundation needed to identify ways in which we can better treat anxiety disorders in which fear condition plays a role, such as post-traumatic stress disorder,” said Bolshakov.