Dissecting connections between chronic stress, inflammation and depression

November 21, 2019

Science Daily/Medical College of Georgia at Augusta University

Chronic stress can inflame our brain, destroy the connections between our neurons and result in depression, scientists say.

Now they are working to better understand how the destructive cycle happens and how best to intervene.

Even powerful, prescription anti-inflammatory drugs that should help break the connectivity between chronic stress and inflammation don't help many patients with depression, says Dr. Anilkumar Pillai, neuroscientist in the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University.

Two new grants totaling about $2.4 million from the National Institute of Mental Health are helping Pillai further explore his increasing evidence that the problem may start with the impact stress has on our bodies and the body's fundamental, frontline and nonspecific immune response called innate immunity.

The complement system, named because it was first found to help the immune system fight invaders, is part of this innate immune response, and Pillai has found elevated levels of C3 -- which he calls the hub of all complement activation pathways -- in both the brains of people with depression and animal models.

The complement system also has the important job during development of removing bad connections between neurons, and there is good evidence the same thing happens in a developed brain in problems like major depressive disorder and Alzheimer's, when losing these important connections, called synapses, is problematic rather than helpful.

"You have to have a functioning complement system during development," says Pillai. But he and his research colleagues have put together some of the first evidence that in depression, the complement also is active, causing inflammation and synaptic loss in the prefrontal cortex, an area of the brain important to working memory, personality and executive function. "Under chronic stress you are losing your synapses," he says.

C3 is known to play a key role in inflammation in the brain, and microglia, the resident immune cells in the brain, are known to use C3 during brain development to eliminate synapses.

"We expect that chronic stress increases C3," Pillai says as he continues to put the complex puzzle together. Now he and his colleagues want to know where the high C3 is coming from, whether it's the immune cells called monocytes, circulating in the body in response to stress, or the microglia. It may turn out that microglia are the direct source but changes chronic stress makes to the body are the instigators in this vicious, destructive circle.

Studies have shown that chronic stress is a major factor in depression, says Pillai. In fact, people with physical health problems like cancer or heart disease where inflammation also is a major factor, often develop depression, and at least one reason is that high levels of inflammation that are impacting the body also may be affecting the brain, Pillai says.

"They are basically bidirectionally fueling each other," he says. "It's not everyone; it's a subset of individuals with these conditions."

In a paper published in March 2018 in the journal Brain, Behavior and Immunity, Pillai's lab reported significant increases in C3 expression in the prefrontal cortex of depressed individuals who had committed suicide. They also found increased C3 expression in the prefrontal cortex of mice in response to chronic stress but that mice lacking C3 did not get depressive-like behavior in response. In fact, just causing overexpression of C3 in certain areas of the prefrontal cortex caused depression-like behavior, even without the stress.

Their early findings indicate that when NF-kappa B, a transcription factor that regulates both innate and adaptive immunity and is implicated as a key regulator of inflammation in depression, is inhibited, stress-induced increases of C3 in a mouse's prefrontal cortex are reduced. Depleting microglia appears to do essentially the same thing.

This time they are bringing down both levels of C3 and its receptors in microglia as well as peripheral monocytes to further parse the role of the complement system and the source of C3.

Pillai's collaborators include Dr. Stephen Tomlinson, an expert in the complement system and central nervous system inflammation, who is interim chair of the Department of Microbiology and Immunology at the Medical University of South Carolina College of Medicine. One of the many things Tomlinson's lab does is generate complement inhibitors, including drugs that block C3's activation through different pathways, which Pillai is using for these studies and will give additional insight into how activation is happening.

If the complement inhibitors work in animal models, some iteration of these research drugs may also one day help people with depression based on their level of inflammation, Pillai says.

The second NIMH grant is enabling additional studies of how microglia get activated and Pillai suspects it's interferon alpha circulating in the body that get the microglia and C3 going.

Interferon alpha is a drug used to treat maladies like cancer and hepatitis, but it's also a natural protein that stimulates the immune system to kill things like melanoma and viral infections.

High levels of interferon alpha have been found in the blood of people with depression, and long-term interferon alpha treatment for problems like cancer or chronic hepatitis B can trigger depression or other mental health problems. Even healthy lab animals injected with interferon alpha exhibit depressive symptoms.

The MCG scientists have seen treatment with an interferon receptor antibody reduce social-deficient and depression-like behavior in mice exposed to chronic stress.

The new studies will enable further exploration of their hypothesis that increased interferon alpha activation in the body by stress activates microglia and their C3 production in the brain, which leads to loss of neuron connections and depressed behavior. These studies include use of an interferon receptor antibody to block its action. The fact that interferon alpha goes up in the face of chronic stress is another indicator the body doesn't like stress, Pillai notes.

Immune cells in the brain are typically not as reactive as those circulating in the rest of the body, but stress definitely gets their attention, Pillai says. The major immune function of C3 is mediated through microglia in the brain and monocytes throughout the body, another reason he wants to knock out C3 in both cell types to see the effect.

Current anti-inflammatory therapies have focused on inflammation generated by adaptive immunity, an immune response specific to some invader like a bacterium, rather than less specific innate immunity. But innate immunity is becoming a target in other conditions like cancer and cardiovascular disease, and its role in both inflammation and synapse regulation peaked Pillai's interest in its role in depression.

https://www.sciencedaily.com/releases/2019/11/191121163326.htm

A new link between migraines, opioid overuse may be key to treating pain

November 20, 2019

Science Daily/University of Illinois at Chicago

Researchers have discovered that a peptide links together migraine pain and pain induced by opioid overuse.

About 10% of the world population suffers from migraine headaches, according to the National Institute of Neurological Disorders and Stroke. To alleviate migraine pain, people are commonly treated with opioids. But, while opioid treatment can provide temporary pain relief for episodic migraines, prolonged use can increase the frequency and severity of painful migraines.

Researchers have tried to understand how opioids cause this paradoxical increase in pain for a decade, but the mechanism remained elusive -- until now.

Researchers at the University of Illinois at Chicago and colleagues discovered that a peptide -- small chains of amino acids that can regulate many behaviors and brain signaling pathways -- links together migraine pain and pain induced by opioid overuse.

Their findings are published in the journal Molecular and Cellular Proteomics.

Amynah Pradhan, senior author and UIC associate professor of psychiatry at the College of Medicine said, "Endorphin is an example of a peptide that signals the brain to give a 'runner's high.' However, not all peptides signal for pleasant outcomes. Pituitary adenylate cyclase-activating peptide, or PACAP, is a peptide that can induce migraines in migraine-prone individuals. Because the overuse of opioids can lead to worse migraines, we wanted to determine whether opioid-induced pain changed the amounts of peptides in the brain and understand if pain from migraines and opioid overuse shared any peptides in common."

To study these peptides, Pradhan and her colleagues, including researchers at the University of Illinois at Urbana-Champaign, developed two animal models: migraine pain and opioid overuse pain, both in mouse models. Using mass spectrometry to identify peptides and their quantities in the animal samples, they found only a few peptides were altered in both models. PACAP was one of them.

"We were amazed to find PACAP in both models," Pradhan said. "This study validates prior work on PACAP's role in migraine pain and, more importantly, is the first to identify PACAP as a factor in opioid-induced pain. It is also significant that the PACAP increase was seen in major pain processing sites of the brain, in both models.

"These findings provide strong evidence that PACAP is involved in both migraine and opioid-overuse pain. We finally understand a mechanism through which opioids may exacerbate migraines -- through PACAP."

Pradhan said these findings can inform the development of real-world treatments.

"Companies are developing therapies for migraine pain right now," Pradhan said. "There are clinical trials underway to test antibodies targeting PACAP and a PACAP-binding receptor. Based on our data, these therapies may be extremely effective for people that have used opioids to treat their migraines."

This research may benefit people suffering from non-migraine pain as well, she said, as people with chronic pain also experience opioid-induced pain after overuse.

https://www.sciencedaily.com/releases/2019/11/191120131307.htm

Earthquake-like brain-wave bursts found to be essential for healthy sleep

Findings link healthy sleep to brain-wave bursts that mathematically mimic earthquakes

November 14, 2019

Science Daily/PLOS

New research in rats shows that cortical arousals and brief awakenings during sleep exhibit non-equilibrium dynamics and complex organization across time scales necessary for spontaneous sleep-stage transitions and for maintaining healthy sleep. Prof. Plamen Ch. Ivanov of Boston University and colleagues present these findings in PLOS Computational Biology.

Sleep is traditionally considered to be a homeostatic process that resists deviation from equilibrium. In that regard, brief episodes of waking are viewed as perturbations that lead to sleep fragmentation and related sleep disorders. While addressing aspects of sleep regulation related to consolidated sleep and wake and the sleep-wake cycle, the homeostatic paradigm does not account for the dozens of abrupt sleep-stage transitions and micro-states within sleep stages throughout the night. Ivanov and colleagues hypothesized that, while sleep is indeed homeostatic at time scales of hours and days, non-equilibrium dynamics and criticality underlie sleep micro-architecture at shorter time scales.

To test this hypothesis, the researchers collected electroencephalogram (EEG) recordings of brain activity over multiple days in normal rats and in rats with injuries to the parafacial zone, a brain region that helps regulate sleep. They analyzed the bursting dynamics of brain activity patterns known as theta waves and delta waves, which are seen in both sleeping rats and humans.

Their empirical findings and modeling indicate that arousals from sleep are a manifestation of an intrinsic non-equilibrium sleep regulatory mechanism related to self-organization of neuronal assemblies. This mechanism acts at time scales of seconds and minutes and stays on track via continuous bursts in brain wave rhythms.

The study also suggests that maintaining a non-equilibrium critical state is essential for the sleep-regulation system's flexibility to spontaneously activate multiple transitions between different sleep stages and between sleep and brief wakefulness throughout the sleep period. Such critical state is also necessary for the complex sleep micro-architecture that is increasingly recognized to be characteristic of healthy sleep. The observed critical behavior in sleep draws parallels to other non-equilibrium systems at criticality, such as earthquakes.

"Paradoxically, we find that the 'resting' state of healthy sleep is maintained through bursts in cortical rhythm activity that obey similar temporal organization, statistics, and mathematical laws as earthquakes," Ivanov says. "Our findings serve as building blocks to better understand sleep, and could help improve detection and treatment of sleep disorders."

https://www.sciencedaily.com/releases/2019/11/191114141237.htm

Consensus report shows burnout prevalent in health care community

October 23, 2019

Science Daily/Vanderbilt University Medical Center

Clinician burnout is affecting between one-third and one-half of all of U.S. nurses and physicians, and 45 to 60% of medical students and residents, according to a National Academy of Medicine (NAM) report released today.

Vanderbilt University Medical Center is among 32 institutions and foundations that sponsored the 296-page report, "Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being," which investigates the causes of widespread clinician burnout and offers solutions to address the problem at its source.

"There's an all too direct connection between clinician burnout and health care safety and quality. While clinician burnout isn't a new problem, its worsening prevalence and impact are due to system factors inherent in the modern health care system," said Matthew Weinger, MD, professor of Anesthesiology and Norman Ty Smith Chair in Patient Safety and Medical Simulation at VUMC, and a member of the NAM authoring committee for the new report.

"The Committee came to realize that addressing clinician burnout will require a deliberate and substantive health care system redesign with a focus on those activities that deliver the most value to patients while enabling and empowering clinicians to deliver high-quality care," he said.

The report discusses key issues that need to be addressed:

·      Clinician burnout needs to be tackled early in professional development and special stressors in the learning environment need to be recognized. Leaders in health care and health professions education have a responsibility to foster, monitor and continuously improve work and learning environments.

·      While some health care technologies appear to contribute to clinician burnout (poorly designed electronic health record systems, for example), there is real potential for well-designed and implemented technologies to help reduce burnout.

·      Federal and state governments, other payors and regulators and the health care industry itself have important roles to play in preventing clinician burnout. Increasing administrative burdens and distracting clinicians from the care of their patients can directly affect burnout.

·      Medical societies, state licensing boards, specialty certification boards, medical education and health care organizations all need to take concrete steps to reduce the stigma for clinicians seeking help for psychological distress and make assistance more easily available.

The report concludes with goals and recommendations centered on creating more positive work and learning environments, reducing administrative burden, enabling technology solutions, providing more support to clinicians and learners, and investing in research to address clinician burnout.

The new report is the latest in a series that includes the landmark volumes, "To Err Is Human: Building a Safer Health System" (2000) and "Crossing the Quality Chasm: A New Health System for the 21st Century" (2001).

Report: https://www.nap.edu/catalog/25521/taking-action-against-clinician-burnout-a-systems-approach-to-professional

https://www.sciencedaily.com/releases/2019/10/191023172121.htm

Science demonstrates that what doesn't kill you makes you stronger

Researchers find that early-career failure promotes future professional success

October 1, 2019

Science Daily/Northwestern University

Through advanced data analysis, researchers have established a causal relationship between failure and future success.

Scientists at Northwestern University's Kellogg School of Management have established a causal relationship between failure and future success, proving German philosopher Friedrich Nietzsche's adage that "what does not kill me makes me stronger."

The researchers utilized advanced analytics to assess the relationship between professional failure and success for young scientists. They found, in contrast to their initial expectations, that failure early in one's career leads to greater success in the long term for those who try again.

"The attrition rate does increase for those who fail early in their careers," lead author Yang Wang said. "But those who stick it out, on average, perform much better in the long term, suggesting that if it doesn't kill you, it really does make you stronger."

The study, "Early-career setback and future career impact," will be published Oct. 1, in Nature Communications.

The findings provide a counter-narrative to the Matthew Effect, which posits a "rich get richer" theory that success begets more success.

"It turns out that, historically, while we have been relatively successful in pinpointing the benefits of success, we have failed to understand the impact of failure," said Dashun Wang, corresponding author and associate professor of management and organizations at Kellogg.

Methodology and findings

Researchers analyzed records of scientists who, early in their careers, applied for R01 grants from the National Institutes of Health (NIH) between 1990 and 2005. They utilized the NIH's evaluation scores to separate individuals into two groups: (1) the "near-misses" whose scores were just below the threshold that received funding and (2) the "just-made-its" whose scores were just above that threshold.

Researchers then considered how many papers each group published, on average, over the next 10 years and how many of those papers turned out to be hits, as determined by the number of citations those papers received.

Analysis revealed that individuals in the near-miss group received less funding, but published just as many papers, and more hit papers, than individuals in the just-made-it group.

The researchers found that individuals in the near-miss funding group were 6.1% more likely to publish a hit paper over the next 10 years compared to scientists in the just-made-it group.

"The fact that the near-miss group published more hit papers than the just-made-it group is even more surprising when you consider that the just-made-it group received money to further their work, while the near-miss group did not," said Benjamin Jones, study co-author and the Gordon and Llura Gund Family Professor of Entrepreneurship at Kellogg.

Researchers wondered whether the effect could be attributed to a "weed-out" phenomenon -- that the early-career failure caused some scientists in the near-miss group to exit the field, leaving only the most-determined members. Further analysis revealed that while the attrition rate after failure was 10 percent higher for the near-miss group, that alone could not account for the greater success later in their careers.

After testing a number of other possible explanations for the long-term success of the near-miss group, researchers could not find any supporting evidence for any of their hypotheses, suggesting other unobservable factors, such as grit or lessons learned, might be at play.

The research does not contradict the Matthew Effect, but rather suggests a complementary path for those who fail.

"There is value in failure," Dashun Wang said. "We have just begun expanding this research into a broader domain and are seeing promising signals of similar effects in other fields."

All three researchers involved in the study are faculty in Northwestern's Center for the Science of Science and Innovation, which is dedicated to understanding the conditions that lead to scientific success and failure.

https://www.sciencedaily.com/releases/2019/10/191001084008.htm

Heterogeneity in the workplace: 'Diversity is very important to us -- but not in my team'

September 12, 2019

Science Daily/University of Basel

Diversity in the workplace is highly sought in theory, but often still lacking in practice. A new study shows that people tend to favor diversity for others, but prefer to work with people who are as similar to themselves as possible. A team of researchers from the universities of Basel and Koblenz-Landau published their report in the Journal of Experimental Social Psychology.

Today, many large corporations tout the importance of diversity on their websites, but current statistics show that the typical manager still tends to be white and male. Obviously, there is a dissonance between the desire to bring about diversity and corporate reality.

A team of researchers led by Dr. Mariela Jaffé from the Department of Psychology at the University of Basel studied this discrepancy from a social psychology perspective. This involved conducting four studies with a sampling of 605 people in total. The results showed a significant difference in how people select colleagues for themselves versus for other people.

How do people value diversity?

People have a wide spectrum of opinions concerning diversity. On the one hand, people see value in diversity, which can contribute a variety of perspectives, new ideas and innovative solutions. On the other hand, they assume that it might be difficult to work with someone who has completely different views, speaks a different language, or has a different style of work.

The actual value they attribute to diversity depends on the decision-making perspective. Building on current theories, the researchers have shown that doubts about the practicability of diversity have a greater weight if a person is directly affected. In other words, when a person's own work group is involved, they tend to prefer team members who are similar to themselves, whereas when people make decisions for other people, these reservations play a lesser role. Typically, a person will then put together a more diverse team.

Consequences of differing preferences

This leads to the conclusion that organizations could become more diverse if hiring and team decisions were not (only) made by those directly affected, but (also) by other people who are not directly involved in the group's daily work later.

"Research shows that people's perception of and the importance they attach to diversity have key implications for people's decision making," explains lead author Dr. Jaffé. "In a next step it would be important to gain a better understanding of the evaluation of diversity to discuss and resolve concerns about potential disadvantages. This way, people may then be more willing to include dissimilar people in their own teams."

https://www.sciencedaily.com/releases/2019/09/190912120539.htm

A little kindness goes a long way for worker performance and health

September 10, 2019

Science Daily/Penn State

Small gestures of kindness by employers can have big impacts on employees' health and work performance, according to an international team of researchers. The team specifically examined the effects of employers enhancing the lunches of bus drivers in China with fresh fruit and found that it reduced depression among the drivers and increased their confidence in their own work performance.

"An ultimate solution to improve worker performance and health could be big pay raises or reduced workloads, but when those solutions aren't feasible, we found that even small offerings can make a big difference," said Bu Zhong, associate professor of journalism at Penn State.

According to Zhong, bus drivers are vulnerable to specific health problems due in large part to their stressful working environment, which often includes irregular shift schedules, unpredictable traffic conditions and random meal times. In addition, the sedentary nature of driving and continuous whole-body vibration contributes to fatigue, musculoskeletal problems such as lower-back pain, cardiovascular diseases and gastrointestinal issues.

Zhong and his colleagues conducted an experiment with 86 Shenzen bus drivers. During the experiment, on-duty bus drivers were given, in addition to their typical box lunch which includes no fruit, a serving of fresh fruit -- either an apple or a banana -- for three weeks. The cost of the fruit was 73 cents per meal.

The team distributed surveys to the bus drivers at three time intervals -- one week before the experiment began, once in the middle of the three-week-long experiment and one week following the end of the experiment. The findings appear today in the International Journal of Occupational Safety and Ergonomics.

The researchers assessed depression with a personal health questionnaire that is recommended by the U.S. Centers for Disease Control and Prevention. The scale consisted of eight items, asking the participants to rate, for example, how often during the past two weeks they felt down, depressed or hopeless, and had trouble falling or staying asleep.

"Bus drivers reported significantly decreased depression levels one week after the experiments ended compared to one week before it began," said Zhong.

The team measured self-efficacy -- perceived confidence and ability to implement the necessary actions and tasks so as to achieve specific goals -- using the 10-item General Self-Efficacy Scale. Items on this scale included, "I can always manage to solve difficult problems if I try hard enough" and "I can usually handle whatever comes my way."

"We found that self-efficacy was significantly higher in the middle of the experiment week than in the week after the experiment ended," said Zhong.

Zhong concluded that while eating an extra apple at lunchtime may seem trivial, its impact can be large.

"This research suggests that employees can be sensitive to any improvement at the workplace," he said. "Before an ultimate solution is possible, some small steps can make a difference -- one apple at a time."

https://www.sciencedaily.com/releases/2019/09/190910154708.htm

Hiring committees that don't believe in gender bias promote fewer women

August 26, 2019

Science Daily/University of British Columbia

Is gender bias in hiring really a thing?

Opinions vary, but a new study by a UBC psychologist and researchers in France reveals that hiring committees who denied it's a problem were less likely to promote women.

"Our evidence suggests that when people recognize women might face barriers, they are more able to put aside their own biases," said Toni Schmader, a UBC psychology professor and Canada Research Chair in social psychology. "We don't see any favourability for or against male or female candidates among those committees who believe they need to be vigilant to the possibility that biases could be creeping in to their decision-making."

The study was unique in that findings were based on actual decisions made by 40 hiring committees in France, charged with filling elite research positions with the National Committee for Scientific Research (CNRS) for two consecutive years. Past research in this area has relied mostly on hypothetical scenarios, such as presenting a large sample of participants with identical resumés bearing either male or female names and asking who they would hire. By contrast, the decisions made during this study had real impact on scientists' careers.

With cooperation from the CNRS, the researchers were able to first measure how strongly hiring committee members associated men with science. They did this using an "implicit association test" that flashes words on a computer screen and measures how quickly participants are able to assign those words to a particular category. People who make a strong association between men and science have to think a bit longer, and react more slowly, when challenged to pair female-related words with science concepts.

Both men and women on the hiring committees tended to show the science = male association, which is difficult to hide in such a test.

"There's research suggesting that you can document a 'think science, think male' implicit association showing up with kids as early as elementary school," Schmader said. "We learn associations from what we see in our environment. If we don't see a lot of women who are role models in science, then we learn to associate science more with men than women."

These implicit associations are distinct from people's explicit beliefs about women in science. In a separate survey that asked panellists directly whether women in science careers are impacted by such things as discrimination and family constraints, some hiring committees minimized those issues. Others acknowledged them.

When the researchers compared these implicit and explicit beliefs with the actual hiring outcomes, they learned that committees attuned to the barriers women face were more likely to overcome their implicit science/male associations when selecting candidates for the job. Among committees that believed "science isn't sexist," those which implicitly associated science more with men promoted fewer women. The difference was especially pronounced in Year 2 of the study, when committee members would have been less conscious of the fact that their selections were being studied.

The findings show that awareness and acknowledgement of the barriers women face might be key to making sure implicit biases don't affect hiring decisions. They also point to the importance of educating hiring committees about gender bias and how to guard against it, Schmader said.

https://www.sciencedaily.com/releases/2019/08/190826112653.htm

Maximizing alertness and productivity on the nightshift

August 9, 2019

Science Daily/University of South Australia

If you're one of Australia's 1.4 million shiftworkers, eating at irregular times is just par for the course -- but have you ever stopped to think about the impact this might have on your body?

In a new research study by the University of South Australia, researchers have investigated whether altering food intake during the nightshift could optimise how shiftworkers feel during the night and reduce their sleepiness.

Testing the impact of either a snack, a meal, or no food at all, the study found that a simple snack was the best choice for maximising alertness and productivity.

Lead researcher and UniSA PhD candidate Charlotte Gupta says the finding has the potential to help thousands of shiftworkers who work during the night.

"In today's 24/7 economy, working the nightshift is increasingly common, with many industries -- health care, aviation, transport and mining -- requiring employees to work around the clock," Gupta says.

"As a nightshift worker, finding ways to manage your alertness when your body is naturally primed for sleep can be really challenging.

"We know that many nightshift workers eat on-shift to help them stay awake, but until now, no research has shown whether this is good or bad for their health and performance.

"This is the first study to investigate how workers feel and perform after eating different amounts of food.

"The findings will inform the most strategic eating patterns on-shift and can hopefully contribute to more alert and better performing workers."

In Australia, of the 1.4 million shiftworkers, 15 per cent (or over 200,000) regularly work a night or evening shift. Working at night-time conflicts with a person's internal circadian clock, making it harder to stay focused and awake. Managing fatigue is therefore critical for workplace health and safety.

Over a 7-day simulated shiftwork protocol, the study assessed the impact of three eating conditions (a meal comprising 30 per cent of energy intake over a 24-hour period (for example, a sandwich, muesli bar, and apple); a snack comprising 10 percent of energy intake (for example, just the muesli bar and apple); and no food intake at all) each consumed at 12:30 am. The 44 participants were randomly split into the three test-conditions and were asked to report on their levels of hunger, gut reaction and sleepiness.

The results showed that while all participants reported increased sleepiness and fatigue, and decreased vigour across the nightshift, consuming a snack reduces the impact of these feelings more so than a meal or no food at all. The snack group also reported having no uncomfortable feelings of fullness as noted by the meal group.

Gupta says the next step in the research is to investigate the different types of snacks and how they affect shiftworkers differently.

"Now that we know that consuming a snack on nightshift will optimise your alertness and performance without any adverse effects, we're keen to delve more into the types of snacks shiftworkers are eating," Gupta says.

"Lots of shiftworkers snack multiple times over a nightshift, and understanding the different macronutrient balances is important, especially as many report consuming foods high in fat, such as chips, chocolate and fast foods.

"We're keen to assess how people feel and perform after a healthy snack versus a less-healthy, but potentially more satisfying snack like chocolate or lollies.

"Ultimately, the goal is to help Australian shiftworkers on the nightshift to stay alert, be safe, and feel healthy."

https://www.sciencedaily.com/releases/2019/08/190809104947.htm

Concussion alters how information is transmitted within the brain

December 3, 2019

Science Daily/Radiological Society of North America

Damage from concussion alters the way information is transmitted between the two halves of the brain, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA).

Research has shown that the corpus callosum, a bundle of nerve fibers that carries signals between the brain's left and right hemispheres, is vulnerable to damage from mild traumatic brain injury, commonly known as concussion. Less is known about the impact of this damage on cognitive function.

To learn more, researchers at New York University (NYU) School of Medicine in New York City compared the condition of the corpus callosum in 36 patients with recent concussion to that of 27 healthy controls. They studied the participants' brains with two innovative advances, including an MRI technique that uses measures of water diffusion to provide a microscopic view of the brain's signal-carrying white matter.

"Looking at how water molecules are diffusing in the nerve fibers in the corpus callosum and within the microenvironment around the nerve fibers allows us to better understand the white matter microstructural injury that occurs," said study co-author Melanie Wegener, M.D., resident physician at NYU Langone Health in New York City.

Dr. Wegener and colleagues combined the MRI findings with results from the study's second innovative advance, called an Interhemispheric Speed of Processing Task, a test developed at NYU Langone that evaluates how well the two hemispheres in the brain communicate with each other.

For the test, the participants were told to sit in a chair and focus their gaze on the letter X that was displayed on a screen directly in front of them. The researchers then flashed three-letter words to the right or the left of the X and asked the participants to say those words as quickly as possible. When the researchers evaluated this reaction time in both patients with concussion and healthy controls, they noticed an interesting phenomenon.

"There is a definite and reproducible delay in reaction time to the words presented to the left of the X compared with words presented to the right visual field," Dr. Wegener said. "This shows it takes time for information to cross the corpus callosum from one hemisphere to the other, which is measured by the difference in response time between words presented to different sides of our visual field."

This delay is likely due to the fact that language function is most often located in the brain's left hemisphere. This means that information presented to the left visual field is first transmitted to the right visual cortex in the brain and then has to cross over the corpus callosum to get to the left language center. In contrast, words that are presented to the right visual field do not need to cross the corpus callosum.

Performance on the test correlated with brain findings on MRI. In the healthy controls, reaction time corresponded with several diffusion measures in the splenium, an area of the corpus callosum located between the right visual cortex and the left language center. No such correlation was found in the concussion patients, suggesting microstructural changes relating to injury.

"We saw a correlation between white matter microstructure injury and the clinical status of the patient," Dr. Wegener said. "This information could ultimately help with treatment in patients who have mild traumatic brain injury."

For instance, Dr. Wegener said, patients could undergo MRI immediately after a concussion to see if they experienced any clinically important white matter injury and thus may benefit from early intervention.

"Another thing we can do is use MRI to look at patients' brains during treatment and monitor the microstructure to see if there is a treatment-related response," she said.

https://www.sciencedaily.com/releases/2019/12/191203082910.htm

Concussion recovery not clear cut for children

December 2, 2019

Science Daily/University of Queensland

Sleep problems, fatigue and attention difficulties in the weeks after a child's concussion injury could be a sign of reduced brain function and decreased grey matter.

Researchers from The University of Queensland have studied persistent concussion symptoms and their link to poorer recovery outcomes in children.

UQ Child Health Research Centre Research Fellow Dr Kartik Iyer said information from the study could help parents and doctors assess the risk of long-term disability.

"In the MRI scans of children with persistent concussion symptoms, poor sleep was linked to decreases in brain grey matter and reduced brain function," Dr Iyer said.

"Identifying decreases in brain function can allow us to predict if a child will recover properly.

"This knowledge can help clinicians ensure a child receives targeted rehabilitation such as cognitive behaviour therapy, medication to improve sleep, or safe and new emerging therapies such as non-invasive brain stimulation to potentially reduce symptoms."

Researchers were able to predict with 86 per cent accuracy how decreases in brain function impacted recovery two months post-concussion.

"Generally, children with persistent concussion symptoms will have alterations to their visual, motor and cognitive brain regions but we don't have a clear understanding of how this develops and how it relates to future recovery," Dr Iyer said.

"It can have a serious impact on their return to normal activities, including time away from school, difficulties with memory and attentiveness, disturbances to sleeping habits and changes to mood -- all of which affect healthy brain development."

Most children recover fully after a concussion, but one in 10 has persistent symptoms.

"It is critical that children who receive a head injury see a doctor and get professional medical advice soon after their injury has occurred," he said.

"While playing sports or riding bicycles or scooters, children should wear proper protective head gear to minimise the impact of a head injury."

For children with persistent concussion symptoms, a child-friendly non-invasive brain stimulation therapy is being trialled at UQ's KidStim laboratory.

Families interested in contacting the study team and registering their interest can contact the Acquired Brain Injury team.

https://www.sciencedaily.com/releases/2019/12/191202102046.htm

Concussions in high school athletes may be a risk factor for suicide

November 25, 2019

Science Daily/University of Texas Health Science Center at Houston

Concussion, the most common form of traumatic brain injury, has been linked to an increased risk of depression and suicide in adults. Now new research published by The University of Texas Health Science Center at Houston (UTHealth) suggests high school students with a history of sports-related concussions might be at an increased risk for suicide completion.

The research, which recently appeared in the November issue of the Journal of Affective Disorders, examined the link between self-reported history of concussion and risk factors for suicide completion. It was the first study to include a nationally representative sample of high school students. According to the Centers for Disease Control and Prevention, suicide is the second-leading cause of death in Americans ages 10 to 34.

"It's important to remember that when it comes to concussions, there's no visual test to confirm them. Unfortunately, you can't take your child to have a lab test done to diagnose one," said Dale Mantey, the study's lead author, a doctoral student at UTHealth School of Public Health in Austin.

Common symptoms of a concussion include loss of consciousness, headache, confusion, and change in mood.

The study examined survey data collected from more than 13,000 high school students in the United States. Participants were asked if they had received a concussion related to sports or physical activity in the last year, as well as a range of questions to measure potential suicidal behaviors. Approximately 15% of students surveyed reported having suffered a concussion.

Researchers discovered that teenagers who reported having a concussion in the last year were more likely to report feelings of depression, suicidal ideations, and planned or previous suicide attempts. Of the portion of students who reported a history of concussions, approximately 36% reported they had felt sad or hopeless (compared to 31.1% of all teens) and around 21% had thoughts of suicide (compared to 17%).

Male participants with a reported concussion in the last year were twice as likely to report having attempted suicide and three times more likely to report a history of receiving medical treatment for an attempted suicide than those who did not have a recent concussion.

The study also revealed female students with a history of concussions had greater odds to report all risk factors of suicide. They were more likely to have reported feeling sad or hopeless, having suicidal ideations, a planned suicide attempt, having attempted suicide, and were twice as likely to indicate a history of receiving medical treatment for an attempted suicide compared to females who did not report a concussion in the last year. A recently published article in the journal Pediatrics revealed female high school athletes have higher concussion rates than their male counterparts.

The researchers noted that while the study did control for commonly associated suicide risk factors like sexual orientation and a history of being bullied, it did not account for other risk factors like drug or alcohol use. There were no measures of preconcussion mental health for survey participants.

"Concussions are a traumatic brain injury and they are even worse for young people with developing brains," said Steven H. Kelder, PhD, MPH, senior author and Beth Toby Grossman Distinguished Professor in Spirituality and Healing at UTHealth School of Public Health in Austin. "These injuries can have long-term effects such as memory issues and sleep disturbances."

According to the National Suicide Prevention Lifeline, warning signs of suicide can include talking about feeling hopeless, withdrawing or social isolation, extreme mood swings, and reckless or anxious behavior.

"Everyone needs to be aware of the warning signs and the risks that come with concussions -- parents, teachers, coaches, but also the students themselves," Mantey said. "If there is any concern that a child may have suffered a concussion, it is critical to seek medical attention. If a child is diagnosed with a concussion, everyone in their support network should look for changes in mood or behavior that may be warning signs of reduced mental well-being."

https://www.sciencedaily.com/releases/2019/11/191125145546.htm

How brain injury can lead to post-traumatic stress disorder

UCLA team finds that the brain processes fear differently after injury

November 4, 2019

Science Daily/University of California - Los Angeles

Post-traumatic stress disorder in U.S. military members frequently follows a concussion-like brain injury. Until now, it has been unclear why. A UCLA team of psychologists and neurologists reports that a traumatic brain injury causes changes in a brain region called the amygdala; and the brain processes fear differently after such an injury.

"Is one causing the other, and how does that occur?" asked senior author Michael Fanselow, who holds the Staglin Family Chair in Psychology at UCLA and is the director of UCLA's Staglin Music Festival Center for Brain and Behavioral Health. "We're learning."

Two groups of rats were studied. Through surgery, a concussion-like brain injury was produced in 19 of the rats. Sixteen other rats -- a control group -- also had the surgery, but did not sustain a brain injury. All of the rats were then exposed to a low level of noise, followed by a series of moderate, brief foot shocks. The foot shocks were frightening to the rats, but not very painful, Fanselow said. Because the rats learned to associate the noise with the shock, they became afraid of the noise.

Rats tend to stand still when they experience fear. When they recall a frightening memory, they freeze. Their heart rate and blood pressure go up -- and the stronger the memory, the more they freeze, Fanselow said. On the experiment's third day, the researchers again exposed the rats to the same place where they had been shocked, but did not give them any additional shocks, and studied their reactions.

The rats in the control group did freeze, but the rats that received the brain injury froze for a much longer time. The researchers discovered that even without receiving a foot shock, the rats that had a brain injury showed a fear response to the noise.

"Sensitivity to noise is a common symptom after concussion, which suggested to us that this might partly explain why fear reactions to certain stimuli are increased after brain injury," said Ann Hoffman, a UCLA researcher in psychology and lead author of the research, which is published in the journal Scientific Reports.

"It's almost as if the white noise acted like the shock," Fanselow said. "The noise itself became scary to them, even though it wasn't much noise. They treated it almost like a shock."

The researchers studied the amygdala, which is known to be crucial in learning fear. People with anxiety disorders have increased activity in the amygdala, and PTSD has been linked to increased activity in the amygdala.

The amygdala is made up of neurons, and a rat's amygdala has about 60,000. The researchers discovered that five times as many neurons in the amygdala were active during the white noise in the rats with the brain injury than in the control group, Hoffman said.

The amygdala listens to other brain areas that provide it with information. "The amygdala makes a decision whether a situation is frightening, and when it decides a situation is frightening, it generates a fear response," Fanselow said.

Another new discovery the researchers report is that after the traumatic brain injury, the brain processes sounds from a more primitive part of the brain -- the thalamus -- than from a more sophisticated, highly evolved area of the brain -- the auditory cortex. The thalamus provides a more simplistic, crude representation of sound than the auditory cortex. About four times as many neurons were active in a network from the thalamus to the amygdala in the rats with the injury than in the control group rats, Hoffman said.

The study raises the question of whether it is possible to get the brain's amygdala back to normal following a concussion-like injury, perhaps through behavioral therapy or a pharmaceutical. If so, that could benefit members of the military, as well as civilians who have had serious brain injuries, Fanselow said. He and his team will continue their research in an effort to answer this question.

https://www.sciencedaily.com/releases/2019/11/191104130446.htm

Young adults with PTSD may have a higher risk of stroke in middle age

October 18, 2019

Science Daily/American Heart Association

Young adults who suffer from posttraumatic stress disorder (PTSD) may be more likely to experience a transient ischemic attack (TIA) or major stroke event by middle age, raising the risk as much as other better-known risk factors, according to new research published in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

"Stroke has a devastating impact on young patients and their families, many of whom struggle to cope with long-term disability, depression and economic loss during their most productive years," said Lindsey Rosman, Ph.D., lead author of the study and assistant professor of medicine in the division of cardiology at the University of North Carolina School of Medicine in Chapel Hill. "Ten to 14% of ischemic strokes occur in adults ages 18 to 45, and we don't really have a good understanding of the risk factors for stroke in this age group."

While PTSD has previously been shown to increase the risk of heart disease and stroke in older adults, this is the first study to demonstrate a link between trauma-induced stress disorders and the risk of TIA and stroke in young and middle-aged adults, an age group that has experienced a striking increase in stroke events over the past decade.

Although this study was conducted solely in veterans, PTSD is a debilitating mental condition that affects nearly 8 million adults in the U.S. and about 30 percent of veterans. People who observe or directly experience a traumatic event such as sexual assault, gun violence/mass shooting, military combat or a natural disaster may develop long-lasting symptoms of anxiety, avoidance, hypervigilance, anger/irritability, flashbacks and nightmares. "PTSD is not just a veteran issue, it's a serious public health problem," Rosman said.

Researchers analyzed medical data from more than one million young and middle-aged veterans enrolled in healthcare services provided by the Veterans Health Administration (mostly males, age 18-60, average age of 30, 2 out of 3 white) and had served in recent conflicts in Iraq and Afghanistan. None had previously experienced a TIA or stroke.

During 13 years of follow-up, 766 veterans had a TIA, and 1,877 had an ischemic stroke. Researchers also found:

·      29% were diagnosed with PTSD, and veterans with PTSD were twice as likely to have a TIA, raising the risk more than established risk factors such as diabetes and sleep apnea.

·      Veterans with PTSD were 62% more likely to have a stroke, raising the risk more than lifestyle factors such as obesity and smoking.

·      Veterans with PTSD were more likely to engage in unhealthy behaviors, such as smoking and getting little exercise, that raise the rise for stroke.

·      Even after adjusting for multiple stroke risk factors, co-existing psychiatric disorders, such as depression and anxiety, as well as drug and alcohol abuse, veterans with PTSD were still 61% more likely to have a TIA and 36% more likely to have a stroke than veterans without PTSD.

·      There was a stronger link between PTSD and stroke in men than in women.

"Clinicians should be aware that mental health conditions such as PTSD are increasingly prevalent among young people and may have major implications for their risk of stroke," Rosman said. "Our findings raise important questions about whether early recognition and successful treatment of PTSD can prevent or decrease the likelihood of developing stroke in those exposed to violence, trauma and severe adversity."

Although the study showed a strong relationship between PTSD and early TIA and stroke, it wasn't designed to prove that PTSD causes either condition. Additionally, because the analysis was conducted in younger veterans, the results may not be generalizable to non-veterans or older adults who may have more conventional stroke risk factors, such as atrial fibrillation and heart failure.

"We need to improve stroke prevention in young adults by developing targeted screening programs and age-appropriate interventions. Addressing mental health issues including PTSD may be an important part of a broader public health initiative to reduce the growing burden of stroke in young people," Rosman said.

https://www.sciencedaily.com/releases/2019/10/191018181023.htm

Widely available drug reduces head injury deaths

Early treatment with tranexamic acid could save 'hundreds of thousands of lives worldwide'

October 15, 2019

Science Daily/London School of Hygiene & Tropical Medicine

A low cost and widely available drug could reduce deaths in traumatic brain injury patients by as much as 20%, depending on the severity of injury, according to a major study published in The Lancet. [1] The researchers say that tranexamic acid (TXA), a drug that prevents bleeding into the brain by inhibiting blood clot breakdown, has the potential to save hundreds of thousands of lives.

Led by the London School of Hygiene & Tropical Medicine, the global randomised trial included more than 12,000 head injury patients who were given either intravenous tranexamic acid or a placebo. [2] It found that administration of TXA within three hours of injury reduced the number of deaths. This effect was greatest in patients with mild and moderate traumatic brain injury (20% reduction in deaths), while no clear benefit was seen in the most severely injured patients. The trial found no evidence of adverse effects and there was no increase in disability in survivors when the drug was used. [3,4,5]

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year. [6] The CRASH-3 (Clinical Randomisation of an Antifbrinolytic in Significant Head Injury) trial is one of the largest clinical trials ever conducted into head injury. Patients were recruited from 175 hospitals across 29 countries.

Bleeding in or around the brain due to tearing of blood vessels is a common complication of TBI and can lead to brain compression and death. Although patients with very severe head injuries are unlikely to benefit from tranexamic acid treatment because they often have extensive brain bleeding prior to hospital admission and treatment, the study found a substantial benefit in patients with less severe injuries who comprise the majority (over 90%) of TBI cases. [7]

Ian Roberts, Professor of Clinical Trials at the London School of Hygiene & Tropical Medicine, who co-led the study, said: "We already know that rapid administration of tranexamic acid can save lives in patients with life threatening bleeding in the chest or abdomen such as we often see in victims of traffic crashes, shootings or stabbings. This hugely exciting new result shows that early treatment with TXA also cuts deaths from head injury. It's an important breakthrough and the first neuroprotective drug for patients with head injury.

"Traumatic brain injury can happen to anyone at any time, whether it's through an incident like a car crash or simply falling down the stairs. We believe that if our findings are widely implemented they will boost the chances of people surviving head injuries in both high income and low income countries around the world."

Because TXA prevents bleeds from getting worse, but cannot undo damage already done, early treatment is critical. The trial data showed a 10% reduction in treatment effectiveness for every 20-minute delay, suggesting that patients should be treated with TXA as soon as possible after head injury. [8,9]

Antoni Belli, Neurosurgeon and Professor of Trauma Neurosurgery at the University of Birmingham and co-investigator for trial, said: "This is a landmark study. After decades of research and many unsuccessful attempts, this is the first ever clinical trial to show that a drug can reduce mortality after traumatic brain injury. Not only do we think this could save hundreds of thousands of lives worldwide, but it will no doubt renew the enthusiasm for drug discovery research for this devastating condition."

Dr Ben Bloom, Consultant in Emergency Medicine at Barts Health NHS Trust, the UK's largest recruiter into the trial with more than 500 patients enrolled, said: "Treating traumatic brain injury is extremely challenging with very few treatment options available for patients. Thanks to these latest results, which are applicable to patients with head injuries of any cause and of all demographics, clinicians now have a potentially powerful new treatment available to them."

The most common causes of TBI worldwide are road traffic crashes (which predominantly affect young adults) or falls (which are a major problem in older adults), and the incidence is increasing. In both cases, patients can experience permanent disability or death. Representatives from the charity that supports roach crash victims in the UK, Roadpeace, were involved in the design of the trial.

Amy Aeron-Thomas, Justice and Advocacy Manager from Roadpeace and co-author on the paper said: "It's always better to prevent road crashes in the first place, but these results show that if a crash can't be prevented, death can still be avoided. Given the time to treatment implications, it's more important than ever that the post-crash response is as efficient as possible."

CRASH-3 follows successful previous research involving 20,000 trauma patients, which showed that TXA reduced deaths due to bleeding outside of the skull by almost a third if given within three hours. Based on those trial results, tranexamic acid was included in guidelines for the pre-hospital care of trauma patients. However, patients with isolated traumatic brain injury were specifically excluded. [10]

The authors noted some limitations of the trial, including wide confidence intervals despite the large trial size, and the fact that more patients with un-survivable head injuries were included in the trial than anticipated, which diluted the treatment effect.

The trial was jointly funded by the Department for International Development (DFID), the Medical Research Council (MRC), the National Institute for Health Research (NIHR), (through the Department of Health and Social Care), and Wellcome. The early phase of the trial was funded was funded by The JP Moulton Charitable Foundation. [11]

Notes to Editors

1. Tranexamic acid is a low cost and widely available drug as many different companies sell it. Costs vary slightly per country. In the UK, 500mg is roughly £1.55, so the total dose used in CRASH-3 is about £6.20 (https://bnf.nice.org.uk/medicinal-forms/tranexamic-acid.html). In Malaysia, 500mg is 3.30 Malaysian Ringitt (64p) so around £2.50 for the CRASH-3 dose https://www.pharmacy.gov.my/v2/en/apps/drug-price

2. Patients were randomly allocated to receive a loading dose of 1 g of tranexamic acid infused over 10 minutes, started immediately after randomisation, followed by an intravenous infusion of 1 g over 8 hours, or matching placebo.

3. Among patients treated within 3 hours of injury, there was a reduction in the risk of head injury death with tranexamic acid in mild to moderate head injury (RR=0·78 95%CI 0·64-0·95), numbers of deaths can be seen in figure 3 of the paper (TXA group = 166 / 2846 (5.8%), placebo group = 207 / 2769 (7.5%). In severe head injury (RR=0·99, 95%CI 0·91-1·07) there was no clear evidence of a reduction (p-value for heterogeneity 0·030). The impact of baseline GCS in a regression analysis showed evidence (p=0·007) that tranexamic acid is more effective in less severely injured patients.

4. The most common classification system for TBI severity is based on the Glasgow Coma Scale (GCS) score determined at the time of injury. A total score of 3-8 indicates severe TBI, a score of 9-12 indicates moderate TBI, and a score of 13-15 indicates mild TBI.

5. The risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction was similar in the tranexamic acid and placebo groups. There was no evidence that tranexamic acid increased fatal or non-fatal stroke (RR=1.08). The risk of seizures was similar between groups (RR=1.09).

6. Sixty-nine million (95% CI 64-74 million) individuals are estimated to suffer TBI from all causes each year (https://www.ncbi.nlm.nih.gov/pubmed/29701556).

7. Mild TBI occurs with far greater frequency than moderate or severe TBI -- nearly 10-fold the burden of both moderate and severe injury. Of the estimated 69 million TBIs that occur each year, 81% will be mild, 11% will be moderate, and 8% will be severe (https://www.ncbi.nlm.nih.gov/pubmed/29701556).

8. Early treatment was more effective in patients with mild and moderate head injury (p=0·005) but there was no obvious impact of time to treatment in severe head injury (p=0·73). This is consistent with the hypothesis that tranexamic acid improves outcome by reducing intracranial bleeding.

9. The left hand graph of Figure 4 marked "Mild and Moderate GCS score" shows how treatment benefit is related to time on the risk ratio scale. When the treatment effect for mild and moderate patients is modelled using logistic regression with a time treatment interaction term adjusting for GCS, age and systolic blood pressure, the odds ratio is reduced by approximately 10% for every 20 minute delay.

10. A previous trial (CRASH-2) of 20,211 bleeding trauma patients from hospitals in 40 countries showed that TXA reduces bleeding deaths by a third if given soon after injury (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60835-5/fulltext)

11. Funds to support the drug and placebo costs in the run-in phase of the trial were provided by Pfizer.

https://www.sciencedaily.com/releases/2019/10/191015113316.htm

PTSD nearly doubles infection risk

October 15, 2019

Science Daily/Boston University School of Medicine

A new study is the first to examine the relationship between post-traumatic stress disorder (PTSD) and dozens of infection types in a nationwide cohort. Researchers found that PTSD affects infection risks for men and women differently, having, for example, more of an effect on a woman's risk of urinary tract infection and a man's risk of skin infection

First-of-its-kind study finds people with PTSD were 1.8 times as likely to have any infection as those without PTSD, ranging from being 1.3 times as likely to have meningitis, to 1.7 times as likely to have influenza, to 2.7 times as likely to have viral hepatitis.

A new Boston University School of Public Health (BUSPH) study is the first to examine the relationship between post-traumatic stress disorder (PTSD) and dozens of infection types in a nationwide cohort. Published in the journal Epidemiology, it is also the first to find that PTSD affects infection risks for men and women differently, having, for example, more of an effect on a woman's risk of urinary tract infection and a man's risk of skin infection.

"Our study adds to the growing evidence suggesting that PTSD and chronic severe stress are damaging for physical health," says BUSPH doctoral candidate Ms. Tammy Jiang, who led the study. This underscores the public health importance of PTSD prevention and treatment interventions, she says.

Ms. Jiang and colleagues from BUSPH, Aarhus University Hospital in Denmark, the University of Vermont, and the Emory University Rollins School of Public Health used Danish national records to look at the health histories of every Danish-born Danish citizen who received a PTSD diagnosis from 1995 through 2011, and matched each person with a comparison group of Danes of the same sex and age. The researchers then compared the Danes' histories of hospital care for 28 different kinds of infections. After adjusting for other physical and mental health diagnoses and for marriage/registered partnership, the researchers found that people with PTSD were 1.8 times as likely to have any infection than those without PTSD, as well as calculating the increased risk for each of the 28 kinds of infection.

Next, the researchers compared men and women with PTSD. They found that having PTSD had more of an effect on a woman's risk for several kinds of infection -- most notably urinary tract infection -- than on a man's risk. Having PTSD also had more of an effect on a man's risk of certain other kinds of infection, most notably skin infection.

https://www.sciencedaily.com/releases/2019/10/191015131421.htm

Rare sleep disorder common among veterans with PTSD

Findings may provide insight about development of neurodegenerative conditions like Parkinson's disease

October 11, 2019

Science Daily/Oregon Health & Science University

Military veterans with post-traumatic stress disorder or concussion suffer from a thrashing form of sleep behavior at a rate that is far higher than the general population, according to a new study by researchers at the VA Portland Health Care System and Oregon Health & Science University. The finding was published online this week in the journal SLEEP.

Researchers next want to probe whether the disorder, known as REM sleep behavior disorder, or RBD, might provide an early signal of the development of neurodegenerative conditions such as Parkinson's disease.

Normally during sleep that coincides with rapid eye movement, or REM sleep, muscles are effectively paralyzed. In cases of RBD, brain control of muscle paralysis is impaired, resulting in people acting out dreams during REM sleep, sometimes causing injuries to themselves or their partners. It is estimated to effect less than 1% of the general population.

That proportion rose to 9% of the 394 veterans in this study, and further swelled to 21% among those with PTSD.

"This is important because, in the general population, RBD has been linked to Parkinson's disease, and RBD often precedes classic symptoms of Parkinson's by years," said senior author Miranda Lim, M.D., Ph.D., a staff physician at the VA and assistant professor of neurology, medicine and behavioral neuroscience in the OHSU School of Medicine. "We don't know whether veterans who have PTSD and higher rates of RBD will go on to develop Parkinson's, but it is an important question we need to answer."

Researchers suspect chronic stress on the brain may play a role in causing the sleep disorder in veterans with PTSD, as many veterans have been exposed to concussion which potentially accelerates neurodegenerative processes.

Each study participant underwent an overnight sleep study at the VA Portland Health Care System between 2015 and 2017 to determine the presence of dream enactment during episodes of REM sleep. Muscle activity was monitored continuously during the 8 hours of the study in order to diagnose RBD. The study found that those with PTSD had over 2-fold increased odds of RBD compared to veterans without PTSD.

"RBD seems to be highly prevalent in veterans with a history of trauma," said lead author Jonathan Elliott, Ph.D., a research physiologist at the Portland VA and assistant professor of neurology in the OHSU School of Medicine.

Doctors involved in the study, including co-authors Kristianna Weymann, Ph.D., R.N., a clinical assistant professor in OHSU School of Nursing, and Dennis Pleshakov, a student at the OHSU School of Medicine, will continue to track research participants with RBD, looking for early signs of Parkinson's or other neurodegenerative conditions.

Although there are several therapies to ease some of the symptoms of Parkinson's, including tremor and fatigue, so far there has been no definitive therapy to prevent it.

Clinical trials for promising therapies are usually conducted well after patients have been diagnosed with Parkinson's, at a stage which may be too late to reverse the symptoms. Lim said that identifying patients with RBD presents an opportunity to identify people earlier in the disease course, and potentially provides a more viable window to test promising interventions.

"By the time a patient shows classic symptoms of Parkinson's, it may be too late," Lim said. "If you could intervene when people first start to show RBD, maybe you could prevent later symptoms of Parkinson's."

https://www.sciencedaily.com/releases/2019/10/191011095919.htm

Blood-brain barrier damage occurs even with mild head trauma

September 25, 2019

Science Daily/American Associates, Ben-Gurion University of the Negev

In a new study of adolescent and adult athletes, researchers at Ben-Gurion University of the Negev, Stanford University and Trinity College in Dublin have found evidence of damage to the brain's protective barrier, without a reported concussion.

For the first time, the researchers were able to detect damage to the blood-brain barrier (BBB), which protects the brain from pathogens and toxins, caused by mild traumatic brain injury (mTBI). The results were published this month in the Journal of Neurotrauma.

The researchers studied high-risk populations, specifically professional mixed martial arts (MMA) fighters and adolescent rugby players, to investigate whether the integrity of the blood-brain barrier (BBB) is altered and to develop a technique to better diagnose mild brain trauma.

"While the diagnosis of moderate and severe TBI is visible through magnetic resonance imaging [MRI] and computer-aided tomography scanning [CT], it is far more challenging to diagnose and treat mild traumatic brain injury, especially a concussion which doesn't show up on a normal CT," explains Prof. Alon Friedman, M.D., Ph.D. Dr. Friedman is a groundbreaking neuroscientist and surgeon, who established the Inter-Faculty Brain Sciences School at BGU.

The study shows that mild impact in professional MMA and adolescent rugby can still lead to a leaky BBB. If in a larger study the results are similar, the brain imaging techniques being developed could be used to monitor athletes to better determine safer guidelines for "return to play."

In this study, MMA fighters were examined pre-fight for a baseline and again within 120 hours following competitive fight. The rugby players were examined pre-season and again post-season or post-match in a subset of cases. Both groups were evaluated using advanced MRI protocol developed at BGU, analysis of BBB biomarkers in the blood and a mouthguard developed at Stanford with sensors that track speed, acceleration and force at nearly 10,000 measurements per second.

Ten out of 19 adolescent rugby players showed signs of a leaky blood-brain barrier by the end of the season. Eight rugby players were scanned post-match and two had barrier disruptions. The injuries detected were lower than the current threshold for mild head trauma. The researchers were also able to correlate the level of blood-brain barrier damage seen on an MRI with measurements from the mouthguard sensors.

"The current theory today is that it is the outer surface of the brain that is damaged in a concussion since, during an impact, the brain ricochets off of skull surfaces like Jell-O," Dr. Friedman says. "However, we can see now that the trauma's effects are evident much deeper in the brain and that the current model of concussion is too simplistic."

In the next phase of research, the group plans to conduct a similar study in a larger cohort to determine whether BBB disruptions heal on their own and how long that takes.

"It is likely that kids are experiencing these injuries during the season but aren't aware of them or are asymptomatic," Dr. Friedman says. "We hope our research using MRI and other biomarkers can help better detect a significant brain injury that may occur after what seems to be a 'mild TBI' among amateur and professional athletes."

https://www.sciencedaily.com/releases/2019/09/190925133626.htm

Female athletes seek specialty care for concussion later than males

September 17, 2019

Science Daily/Children's Hospital of Philadelphia

Female athletes seek specialty medical treatment later than male athletes for sports-related concussions (SRC), and this delay may cause them to experience more symptoms and longer recoveries. Researchers from the Sports Medicine Program at Children's Hospital of Philadelphia (CHOP), reported these findings after analyzing electronic health records of sports participants aged 7 to 18.

The study raises the question of whether, in youth and high school sports, inequities in medical and athletic trainer coverage on the sidelines are contributing to delayed identification and specialized treatment of concussion for female athletes, leading to more symptoms and longer recovery trajectories. The study was published in the Clinical Journal of Sports Medicine.

"There is speculation in the scientific community that the reasons adolescent female athletes might suffer more symptoms and prolonged recoveries than their male counterparts include weaker neck musculature and hormonal differences," says senior author Christina Master, MD, a pediatric and adolescent primary care sports medicine specialist and Senior Fellow at CHOP's Center for Injury Research and Prevention. "We now see that delayed presentation to specialty care for concussion is associated with prolonged recovery, and that is something we can potentially address."

Dr. Master and her team analyzed a dataset containing records of 192 children between 7 and 18 who were diagnosed with an SRC and seen by a sports medicine specialist. Females took longer to present to specialist care and had longer recovery trajectories than males. The median days to presentation for a subspecialty evaluation was 15 for females with SRC and 9 for males. This delay is important since time to presentation to specialized care greater than 1 week has been described as a factor associated with prolonged recovery.

Five distinct outcomes indicating return to preinjury function were measured to determine "recovery" in this group of athletes. By looking at average-days-to-recovery for female and male patients across these outcomes, researchers found that females returned to school later (4 vs. 3 days), returned to exercise later (13 vs. 7 days), had neurocognitive recovery later (68 vs. 40 days), had later vision and vestibular (balance) recovery (77 vs. 34 days) and returned to full sport far later (119 vs. 45 days).

Importantly, when researchers limited the analysis to those female and male patients that presented to the specialty practice for evaluation within the first 7 days of injury, the differences between males and females on all outcomes disappeared.

In sports where females sustain the highest rates of concussion- -- including those in this cohort of patients -- specifically soccer, basketball, and cheerleading, there is generally less sideline medical coverage for games and inconsistent athletic training coverage for practice because they are categorized as "moderate-risk sports" based on all-cause injury. In stark contrast, many high school leagues require athletic training coverage at all football, ice hockey and men's basketball practices and games.

"It is possible that the lack of athletic training coverage at the time of injury may affect the time to concussion recognition during the first critical hours and days after injury," says Dr. Master. "This period is a window of opportunity where specific clinical management, such as immediate removal from play, activity modification and sub-symptom threshold exercise is correlated with more rapid recovery."

Those who study pediatric concussion have been investigating why some concussions take longer to resolve than others so that they can identify those concussions early and implement appropriate concussion management plans to hopefully prevent persistent post-concussion symptoms. This study builds on that knowledge and suggests a tangible cause and solution: close the gap in athletic training and medical coverage between female and male sports.

https://www.sciencedaily.com/releases/2019/09/190917075828.htm

Routine sparring in boxing can affect brain performance

September 12, 2019

Science Daily/University of Stirling

Routine sparring in boxing can cause short-term impairments in brain-to-muscle communication and decreased memory performance, according to new research.

The findings emerged from a University of Stirling study that assessed boxers before and after a nine-minute sparring session -- where athletes trade punches without the aim of incapacitating each other.

This study, alongside the team's 2016 research into the impact of heading footballs, is one of the first to show that routine impact in sport -- thought to be innocuous -- results in measurable changes in the brain. Experts believe the findings raise further questions around the safety of other sports, where similar routine impacts occur, and say further research is required.

Dr Thomas Di Virgilio, a Lecturer in Sport, led the latest study alongside colleagues in the Stirling Brains multi-disciplinary research team. He said: "There are still questions surrounding the relationship between repetitive routine head impacts -- such as heading in football or sparring in boxing -- and brain health. The truth is that we do not currently know how much impact is safe.

"For many years, a debate has taken place around the safety of boxing, however, these discussions often focus on heavy blows inflicted during competitive fights. In contrast, we looked at subconcussive impacts -- those that are below the concussion threshold -- inflicted during training sessions.

"Our findings are important because they show that routine practices may have immediate effects on the brain. Furthermore, athletes may be at greater risk of injury if the communications between the brain and muscles are impaired."

The team assessed the motor control and cognitive function of 20 boxers and Muay Thai (Thai boxing) athletes before and after a nine-minute sparring session (three rounds of three minutes). Measurements were taken immediately after the session, and then one-hour and 24 hours later.

Motor control was measured using transcranial magnetic stimulation -- which uses magnetic fields to stimulate the nerve cells in the brains of participants -- to understand how it communicates with the muscles. The participants also completed a series of tests (the Cambridge Neuropsychological Test Automated Battery), providing objective measures of cognitive function.

The team found that, one hour after sparring, the participants showed impaired brain-to-muscle communications and decreased memory performance, relative to controls. After 24 hours, these effects returned to baseline.

Dr Di Virgilio added: "We have previously shown that the repetitive heading of footballs results in short-term changes to brain function and this latest study sought to understand whether similar effects were observed in training practices in other sports. Although transient, we found that brain changes observed after sparring are reminiscent of effects seen following brain injury.

"As with our previous research into heading footballs, it is not possible to say whether there is a 'safe' threshold when it comes to the level of impact in sparring. Further research is required to help sportspeople -- and the academic community -- fully understand the dangers posed by subconcussive impacts, routine in sport, and any measures that can be taken to mitigate against these risks."

Dr Di Virgilio worked alongside Stirling colleagues Dr Angus Hunter, Dr Magdalena Ietswaart, Professor Lindsay Wilson and Professor David Donaldson.

Dr Hunter said: "Importantly, this is a breakthrough study using pioneering techniques enabling us to understand how impaired brain to muscle signalling alters electrical recruitment patterns of leg muscle. In the short-term this may negatively affect fine motor control and thus athletic performance."

https://www.sciencedaily.com/releases/2019/09/190912100941.htm