Posts tagged cortisol

About a dozen years ago, scientists discovered that a hormone called ghrelin enhances appetite. Dubbed the “hunger hormone,” ghrelin was quickly targeted by drug companies seeking treatments for obesity — none of which have yet panned out.

MIT neuroscientists have now discovered that ghrelin’s role goes far beyond controlling hunger. The researchers found that ghrelin released during chronic stress makes the brain more vulnerable to traumatic events, suggesting that it may predispose people to posttraumatic stress disorder (PTSD).

Drugs that reduce ghrelin levels, originally developed to try to combat obesity, could help protect people who are at high risk for PTSD, such as soldiers serving in war, says Ki Goosens, an assistant professor of brain and cognitive sciences at MIT, and senior author of a paper describing the findings in the Oct. 15 online edition of Molecular Psychiatry.

“Perhaps we could give people who are going to be deployed into an active combat zone a ghrelin vaccine before they go, so they will have a lower incidence of PTSD. That’s exciting because right now there’s nothing given to people to prevent PTSD,” says Goosens, who is also a member of MIT’s McGovern Institute for Brain Research.

Lead author of the paper is Retsina Meyer, a recent MIT PhD recipient. Other authors are McGovern postdoc Anthony Burgos-Robles, graduate student Elizabeth Liu, and McGovern research scientist Susana Correia.

Stress and fear

Stress is a useful response to dangerous situations because it provokes action to escape or fight back. However, when stress is chronic, it can produce anxiety, depression and other mental illnesses.

At MIT, Goosens discovered that one brain structure that is especially critical for generating fear, the amygdala, has a special response to chronic stress. The amygdala produces large amounts of growth hormone during stress, a change that seems not to occur in other brain regions.

In the new paper, Goosens and her colleagues found that the release of the growth hormone in the amygdala is controlled by ghrelin, which is produced primarily in the stomach and travels throughout the body, including the brain.

Ghrelin levels are elevated by chronic stress. In humans, this might be produced by factors such as unemployment, bullying, or loss of a family member. Ghrelin stimulates the secretion of growth hormone from the brain; the effects of growth hormone from the pituitary gland in organs such as the liver and bones have been extensively studied. However, the role of growth hormone in the brain, particularly the amygdala, is not well known.

The researchers found that when rats were given either a drug to stimulate the ghrelin receptor or gene therapy to overexpress growth hormone over a prolonged period, they became much more susceptible to fear than normal rats. Fear was measured by training all of the rats to fear an innocuous, novel tone. While all rats learned to fear the tone, the rats with prolonged increased activity of the ghrelin receptor or overexpression of growth hormone were the most fearful, assessed by how long they froze after hearing the tone. Blocking the cell receptors that interact with ghrelin or growth hormone reduced fear to normal levels in chronically stressed rats.

When rats were exposed to chronic stress over a prolonged period, their circulating ghrelin and amygdalar growth hormone levels also went up, and fearful memories were encoded more strongly. This is similar to what the researchers believe happens in people who suffer from PTSD.

“When you have people with a history of stress who encounter a traumatic event, they are more likely to develop PTSD because that history of stress has altered something about their biology. They have an excessively strong memory of the traumatic event, and that is one of the things that drives their PTSD symptoms,” Goosens says.

New drugs, new targets

Over the last century, scientists have described the hypothalamic-pituitary-adrenal (HPA) axis, which produces adrenaline, cortisol (corticosterone in rats), and other hormones that stimulate “fight or flight” behavior. Since then, stress research has focused almost exclusively on the HPA axis.

After discovering ghrelin’s role in stress, the MIT researchers suspected that ghrelin was also linked to the HPA axis. However, they were surprised to find that when the rats’ adrenal glands — the source of corticosterone, adrenaline, and noradrenaline — were removed, the animals still became overly fearful when chronically stressed. The authors also showed that repeated ghrelin-receptor stimulation did not trigger release of HPA hormones, and that blockade of the ghrelin receptor did not blunt release of HPA stress hormones. Therefore, the ghrelin-initiated stress pathway appears to act independently of the HPA axis. “That’s important because it gives us a whole new target for stress therapies,” Goosens says.

Pharmaceutical companies have developed at least a dozen possible drug compounds that interfere with ghrelin. Many of these drugs have been found safe for humans, but have not been shown to help people lose weight. The researchers believe these drugs could offer a way to vaccinate people entering stressful situations, or even to treat people who already suffer from PTSD, because ghrelin levels remain high long after the chronic stress ends.

PTSD affects about 7.7 million American adults, including soldiers and victims of crimes, accidents, or natural disasters. About 40 to 50 percent of patients recover within five years, Meyer says, but the rest never get better.

The researchers hypothesize that the persistent elevation of ghrelin following trauma exposure could be one of the factors that maintain PTSD. “So, could you immediately reverse PTSD? Maybe not, but maybe the ghrelin could get damped down and these people could go through cognitive behavioral therapy, and over time, maybe we can reverse it,” Meyer says.

Working with researchers at Massachusetts General Hospital, Goosens’ lab is now planning to study ghrelin levels in human patients suffering from anxiety and fear disorders. They are also planning a clinical trial of a drug that blocks ghrelin to see if it can prevent relapse of depression.

(Source: web.mit.edu)

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.

(Source: news.ucdavis.edu)