How teens deal with stress may affect their blood pressure, immune system

December 13, 2018

Science Daily/Penn State

Most teens get stressed out by their families from time to time, but whether they bottle those emotions up or put a positive spin on things may affect certain processes in the body, including blood pressure and how immune cells respond to bacterial invaders, according to researchers.

The researchers explored whether the strategies adolescents used to deal with chronic family stress affected various metabolic and immune processes in the body. Strategies could include cognitive reappraisal -- trying to think of the stressor in a more positive way -- and suppression, or inhibiting the expression of emotions in reaction to a stressor.

The team found that when faced with greater chronic family stress, teens who used cognitive reappraisal had better metabolic measures, like blood pressure and waist-to-hip ratio. Teens who were more likely to use suppression tended to have more inflammation when their immune cells were exposed to a bacterial stimulus in the lab, even in the presence of anti-inflammatory signals.

Hannah Schreier, assistant professor of biobehavioral health at Penn State, said the results suggest that the coping skills teens develop by the time they are adolescents have the potential to impact their health later in life.

"These changes are not something that will detrimentally impact anyone's health within a week or two, but that over years or decades could make a difference," Schreier said. "That may be how small changes in metabolic or inflammatory outcomes may become associated with poorer health or a greater chance of developing a chronic disease later in life."

Emily Jones, graduate student in biobehavioral health at Penn State, said the results -- recently published in Psychosomatic Medicine -- help therapists and counselors better work with children and adolescents who live in stressful environments.

"Exposure to chronic stress doesn't always lead to poorer health outcomes, in part because of differences among people," Jones said. "As our study findings suggest, there may be ways to help someone be more resilient in the face of stress by encouraging certain emotion regulation strategies. For children in stressful living situations, we can't always stop the stressors from happening, but we may be able to help youth deal with that stress."

Although previous research has linked chronic stress during childhood with such conditions as depression, autoimmune disorders and cardiovascular disease, the researchers said less is known about why some people under chronic stress develop these conditions while others do not. While it was thought that emotional regulation may play a role, the researchers were not sure exactly how.

To better explore how different ways of regulating emotions can affect different aspects of physical health, the researchers gathered data from 261 adolescents between the ages of 13 and 16 years.

The researchers interviewed the participants about the relationships and chronic stress within their families, as well as measured the participants' waist-to-hip ratios and blood pressure. The adolescents also completed questionnaires about how they regulated their emotions.

To measure immune function, the researchers took blood samples from each participant and exposed the blood to a bacterial stimulus -- both with and without the anti-inflammatory substance hydrocortisone -- to see how the immune cells would respond.

The researchers found that under conditions of greater chronic family stress, the immune cells of adolescents who were more likely to use suppression also tended to produce more pro-inflammatory cytokines, molecules that signal to other cells that there is a threat present and that the body's immune system needs to kick into gear.

The cells of these teens produced more cytokines even in the presence of hydrocortisone, an anti-inflammatory substance that usually tells the body to slow down on producing cytokines.

"Cytokines are like messengers that communicate to the rest of the body that added support is needed," Jones said. "So when you have a high level of these pro-inflammatory cytokines, even in the presence of anti-inflammatory messages from cortisol, it may suggest that your body is mounting an excessive inflammatory response, more so than necessary. It suggests that the immune system may not be functioning as it should be."

Meanwhile, the researchers found that adolescents who tended to use cognitive reappraisal while under more family stress had smaller waist-to-hip ratios -- a measurement used as an indicator of health and chronic disease risk -- and lower blood pressure.

"While we would have to follow up with more studies, the results could lend support to the idea that reappraising a situation during times of stress could be beneficial," Jones said. "For a mild stressor, this could be as simple as reframing a bad situation by thinking about it as a challenge or an opportunity for growth."

The researchers added that opportunities for future studies could include looking at the effects of emotion regulation strategies on these metabolic and immune measures over time to tease apart how the family environment shapes emotion regulation, how emotion regulation may itself influence stress exposure, and how chronic family stress and emotion regulation together can affect chronic disease risk in the long run.

https://www.sciencedaily.com/releases/2018/12/181213131236.htm

Running helps brain stave off effects of chronic stress

Exercise protects vital memory and learning functions

February 14, 2018

Science Daily/Brigham Young University

The study finds that running mitigates the negative impacts chronic stress has on the hippocampus, the part of the brain responsible for learning and memory.

Most people agree that getting a little exercise helps when dealing with stress. A new BYU study discovers exercise -- particularly running -- while under stress also helps protect your memory.

The study, newly published in the journal of Neurobiology of Learning and Memory, finds that running mitigates the negative impacts chronic stress has on the hippocampus, the part of the brain responsible for learning and memory.

"Exercise is a simple and cost-effective way to eliminate the negative impacts on memory of chronic stress," said study lead author Jeff Edwards, associate professor of physiology and developmental biology at BYU.

Inside the hippocampus, memory formation and recall occur optimally when the synapses or connections between neurons are strengthened over time. That process of synaptic strengthening is called long-term potentiation (LTP). Chronic or prolonged stress weakens the synapses, which decreases LTP and ultimately impacts memory. Edwards' study found that when exercise co-occurs with stress, LTP levels are not decreased, but remain normal.

To learn this, Edwards carried out experiments with mice. One group of mice used running wheels over a 4-week period (averaging 5 km ran per day) while another set of mice was left sedentary. Half of each group was then exposed to stress-inducing situations, such as walking on an elevated platform or swimming in cold water. One hour after stress induction researchers carried out electrophysiology experiments on the animals' brains to measure the LTP.

Stressed mice who had exercised had significantly greater LTP than the stressed mice who did not run. Edwards and his colleagues also found that stressed mice who exercised performed just as well as non-stressed mice who exercised on a maze-running experiment testing their memory. Additionally, Edwards found exercising mice made significantly fewer memory errors in the maze than the sedentary mice.

The findings reveal exercise is a viable method to protect learning and memory mechanisms from the negative cognitive impacts of chronic stress on the brain.

"The ideal situation for improving learning and memory would be to experience no stress and to exercise," Edwards said. "Of course, we can't always control stress in our lives, but we can control how much we exercise. It's empowering to know that we can combat the negative impacts of stress on our brains just by getting out and running."

https://www.sciencedaily.com/releases/2018/02/180214093823.htm

Stress can lead to risky decisions

Neuroscientists find chronic stress skews decisions toward higher-risk options

November 16, 2017

Science Daily/Massachusetts Institute of Technology

Making decisions that require weighing pros and cons of two choices is dramatically affected by chronic stress, neuroscientists have discovered. In a study of rats and mice, they found stressed animals were far likelier to choose high-risk, high-payoff options. They also found that impairments of a specific brain circuit underlie this abnormal decision making.

MIT neuroscientists have now discovered that making decisions in this type of situation, known as a cost-benefit conflict, is dramatically affected by chronic stress. In a study of mice, they found that stressed animals were far likelier to choose high-risk, high-payoff options.

The researchers also found that impairments of a specific brain circuit underlie this abnormal decision making, and they showed that they could restore normal behavior by manipulating this circuit. If a method for tuning this circuit in humans were developed, it could help patients with disorders such as depression, addiction, and anxiety, which often feature poor decision-making.

"One exciting thing is that by doing this very basic science, we found a microcircuit of neurons in the striatum that we could manipulate to reverse the effects of stress on this type of decision making. This to us is extremely promising, but we are aware that so far these experiments are in rats and mice," says Ann Graybiel, an Institute Professor at MIT and member of the McGovern Institute for Brain Research.

Graybiel is the senior author of the paper, which appears in Cell on Nov. 16. The paper's lead author is Alexander Friedman, a McGovern Institute research scientist.

Hard decisions

In 2015, Graybiel, Friedman, and their colleagues first identified the brain circuit involved in decision making that involves cost-benefit conflict. The circuit begins in the medial prefrontal cortex, which is responsible for mood control, and extends into clusters of neurons called striosomes, which are located in the striatum, a region associated with habit formation, motivation, and reward reinforcement.

In that study, the researchers trained rodents to run a maze in which they had to choose between one option that included highly concentrated chocolate milk, which they like, along with bright light, which they don't, and an option with dimmer light but weaker chocolate milk. By inhibiting the connection between cortical neurons and striosomes, using a technique known as optogenetics, they found that they could transform the rodents' preference for lower-risk, lower-payoff choices to a preference for bigger payoffs despite their bigger costs.

In the new study, the researchers performed a similar experiment without optogenetic manipulations. Instead, they exposed the rodents to a short period of stress every day for two weeks.

Before experiencing stress, normal rats and mice would choose to run toward the maze arm with dimmer light and weaker chocolate milk about half the time. The researchers gradually increased the concentration of chocolate milk found in the dimmer side, and as they did so, the animals began choosing that side more frequently.

However, when chronically stressed rats and mice were put in the same situation, they continued to choose the bright light/better chocolate milk side even as the chocolate milk concentration greatly increased on the dimmer side. This was the same behavior the researchers saw in rodents that had the prefrontal cortex-striosome circuit disrupted optogenetically.

"The result is that the animal ignores the high cost and chooses the high reward," Friedman says.

Circuit dynamics

The researchers believe that this circuit integrates information about the good and bad aspects of possible choices, helping the brain to produce a decision. Normally, when the circuit is turned on, neurons of the prefrontal cortex activate certain neurons called high-firing interneurons, which then suppress striosome activity.

When the animals are stressed, these circuit dynamics shift and the cortical neurons fire too late to inhibit the striosomes, which then become overexcited. This results in abnormal decision making.

"Somehow this prior exposure to chronic stress controls the integration of good and bad," Graybiel says. "It's as though the animals had lost their ability to balance excitation and inhibition in order to settle on reasonable behavior."

Once this shift occurs, it remains in effect for months, the researchers found. However, they were able to restore normal decision making in the stressed mice by using optogenetics to stimulate the high-firing interneurons, thereby suppressing the striosomes. This suggests that the prefronto-striosome circuit remains intact following chronic stress and could potentially be susceptible to manipulations that would restore normal behavior in human patients whose disorders lead to abnormal decision making.

"This state change could be reversible, and it's possible in the future that you could target these interneurons and restore the excitation-inhibition balance," Friedman says.

https://www.sciencedaily.com/releases/2017/11/171116132746.htm

Depression and chronic stress accelerates aging

November 10, 2011

Science Daily/Umeå University

People with recurrent depressions or those exposed to chronic stress exhibits shorter telomeres in white blood cells.

The telomere is the outermost part of the chromosome. With increasing age, telomeres shorten, and studies have shown that oxidative stress and inflammation accelerates this shortening. On this basis it has been suggested that telomere length is a measure of biological aging, and telomere length has subsequently been linked to age-related diseases, unhealthy lifestyle, and longevity.

The research team shows that shorter telomere length is associated with both recurrent depression and cortisol levels indicative of exposure to chronic stress.

"The test revealed that cortisol levels indicative of chronic stress stress are associated with shorter telomeres in both depressed and healthy individuals," says Mikael Wikgren, a doctoral candidate in the research group.

The fact that depressed patients as a group have shorter telomere lengths compared to healthy individuals can be largely explained by the fact that more depressed people than healthy people have disturbed cortisol regulation, which underscores that cortisol regulation and stress play a major role in depressive disorders.

http://www.sciencedaily.com/releases/2011/11/111109093729.htm

Longevity hormone is lower in stressed, depressed women

June 16, 2015

Science Daily/University of California - San Francisco

Women under chronic stress have significantly lower levels of klotho, a hormone that regulates aging and enhances cognition, researchers have found in a study comparing mothers of children on the autism spectrum to low-stress controls.

The researchers found that the women in their study with clinically significant depressive symptoms had even lower levels of klotho in their blood than those who were under stress but not experiencing such symptoms.

The study, published June 16, in Translational Psychiatry, is the first to show a relationship between psychological influences and klotho, which performs a wide variety of functions in the body.

"Our findings suggest that klotho, which we now know is very important to health, could be a link between chronic stress and premature disease and death," said lead author, Aric Prather, PhD, an assistant professor of psychiatry at UCSF. "Since our study is observational, we cannot say that chronic stress directly caused lower klotho levels, but the new connection opens avenues of research that converge upon aging, mental health, and age-related diseases."

Scientists know from their work in mice and worms that, when klotho is disrupted, it promotes symptoms of aging, such as hardening of the arteries and the loss of muscle and bone, and when klotho is made more abundant, the animals live longer.

In previous work, senior author Dena Dubal, MD, PhD, showed that a genetic variant carried by one in five people is associated with having more klotho in the bloodstream, better cognitive function and a larger region of the prefrontal cortex. Carriers also tend to live longer and have lower rates of age-related disease. Dubal and colleagues found that increasing klotho in mice boosted their cognition and increased resilience to Alzheimer-related toxins, suggesting a therapeutic role for klotho in the brain.

The current study included 90 high-stress caregivers and 88 low-stress controls, most of whom were in their 30s and 40s and otherwise healthy. Klotho is known to decline with age, but in this cross-sectional study of relatively young women, this decline only happened among the high-stress women. The low-stress women did not show a significant reduction in klotho with aging.

"Chronic stress transmits risk for bad health outcomes in aging, including cardiovascular and Alzheimer's disease," said Dubal, an assistant professor in the UCSF Department of Neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease. "It will be important to figure out if higher levels of klotho can benefit mind and body health as we age. If so, therapeutics or lifestyle interventions that increase the longevity hormone could have a big impact on people's lives."

The researchers hypothesized that lower levels of klotho could contribute to stress and depression, since klotho acts on a variety of cellular, molecular and neural pathways that link to stress and depression.

http://www.sciencedaily.com/releases/2015/06/150616155903.htm

Early Childhood Trauma Takes Visible Toll On Brain

October 16, 2012

Science Daily/Society for Neuroscience

Trauma in infancy and childhood shapes the brain, learning, and behavior, and fuels changes that can last a lifetime, according to new human and animal research released today. The studies delve into the effects of early physical abuse, socioeconomic status (SES), and maternal treatment. Documenting the impact of early trauma on brain circuitry and volume, the activation of genes, and working memory, researchers suggest it increases the risk of mental disorders, as well as heart disease and stress-related conditions in adulthood.

Findings show:

·      Physical abuse in early childhood may realign communication between key "body-control" brain areas, possibly predisposing adults to cardiovascular disease and mental health problems (Layla Banihashemi, PhD, abstract 691.12).

·      Rodent studies provide insight into brain changes that allow tolerance of pain within mother-pup attachment (Regina Sullivan, PhD, abstract 399.19).

·      Childhood poverty is associated with changes in working memory and attention years later in adults; yet training in childhood is associated with improved cognitive functions (Eric Pakulak, PhD, abstract 908.04).

·      Chronic stress experienced by infant primates leads to fearful and aggressive behaviors; these are associated with changes in stress hormone production and in the development of the amygdala (Mar Sanchez, PhD, abstract 691.10).

Another recent finding discussed shows that:

·      Parent education and income is associated with children's brain size, including structures important for memory and emotion (Suzanne Houston, MA).

"While we are becoming fully aware, in general, of the devastating impact that early life adversity has on the developing brain, today's findings reveal specific changes in targeted brain regions and the long-lasting nature of these alterations," said press conference moderator Bruce McEwen, PhD, from The Rockefeller University, an expert on stress and its effects on early brain development.

"In doing so, this research points not only to new directions for the improved detection and treatment of resulting cognitive impairment, mental health disorders, and chronic diseases, but also emphasizes the importance of preventing early life abuse and neglect in the first place."

http://www.sciencedaily.com/releases/2012/10/121016132113.htm

Could PTSD involve immune cell response to stress?

- February 20, 2014

Science Daily/Ohio State University

Chronic stress that produces inflammation and anxiety in mice appears to prime their immune systems for a prolonged fight, causing the animals to have an excessive reaction to a single acute stressor weeks later, new research suggests.

After the mice recovered from the effects of chronic stress, a single stressful event 24 days later quickly returned them to a chronically stressed state in biological and behavioral terms. Mice that had not experienced the chronic stress were unaffected by the single acute stressor.

hese scientists previously determined that in mice with chronic stress, cells from the immune system were recruited to the brain and promoted symptoms of anxiety. The findings identified a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders – including, potentially, the recurrent anxiety initiated by stress that is a characteristic of PTSD.

The research reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery – the rest of the body – and back to the central nervous system that ultimately influences behavior.

“We haven’t proffered that there is a cellular component to PTSD, but there very well might be. And it’s very possible that it sits in the periphery as we’ve been describing in the mouse,” said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research.

“Our colleagues who study behavior talk about sensitization,” Sheridan said. “Clearly, the repeatedly stressed mice were sensitized. What we’re adding is that sensitization is associated with a specific cell type that resides in the spleen after the initial sensitization.

http://www.sciencedaily.com/releases/2014/02/140220193333.htm