Depression after traumatic brain injury could represent a new, distinct disease

July 5, 2023

Science Daily/Brigham and Women's Hospital

A new study led by Shan Siddiqi, MD, from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, suggests that depression after traumatic brain injury (TBI) could be a clinically distinct disorder rather than traditional major depressive disorder, with implications for patient treatment. The findings are published in Science Translational Medicine.

"Our findings help explain how the physical trauma to specific brain circuits can lead to development of depression. If we're right, it means that we should be treating depression after TBI like a distinct disease," said corresponding author Shan Siddiqi, MD, of the Brigham's Department of Psychiatry and Center for Brain Circuit Therapeutics. "Many clinicians have suspected that this is a clinically distinct disorder with a unique pattern of symptoms and unique treatment response, including poor response to conventional antidepressants -- but until now, we didn't have clear physiological evidence to prove this."

Siddiqi collaborated with researchers from Washington University in St. Louis, Duke University School of Medicine, the University of Padua, and the Uniformed Services University of the Health Sciences on the study. The work started as a side project seven years ago when Siddiqi was motivated by a patient he shared with David Brody, MD, PhD, a co-author on the study and a neurologist at Uniformed Services University. The two started a small clinical trial that used personalized brain mapping to target brain stimulation as a treatment for TBI patients with depression. In the process, they noticed a specific pattern of abnormalities in these patients' brain maps.

The current study included 273 adults with TBI, usually from sports injuries, military injuries, or car accidents. People in this group were compared to other groups who did not have a TBI or depression, people with depression without TBI, and people with posttraumatic stress disorder. Study participants went through a resting-state functional connectivity MRI, a brain scan that looks at how oxygen is moving in the brain. These scans gave information about oxygenation in up to 200,000 points in the brain at about 1,000 different points in time, leading to about 200 million data points in each person. Based on this information, a machine learning algorithm was used to generate an individualized map of each person's brain.

The location of the brain circuit involved in depression was the same among people with TBI as people without TBI, but the nature of the abnormalities was different. Connectivity in this circuit was decreased in depression without TBI and was increased in TBI-associated depression. This implies that TBI-associated depression may be a different disease process, leading the study authors to propose a new name: "TBI affective syndrome."

"I've always suspected it isn't the same as regular major depressive disorder or other mental health conditions that are not related to traumatic brain injury," said Brody. "There's still a lot we don't understand, but we're starting to make progress."

One limitation of the trial is that with so much data, the researchers were not able to do detailed assessments of each patient beyond brain mapping. As a future step, investigators would like to assess participants' behavior in a more sophisticated way and potentially define different kinds of TBI-associated neuropsychiatric syndromes.

Siddiqi and Brody are also using this approach to develop personalized treatments. Originally, they set out to design a new treatment in which they used this brain mapping technology to target a specific brain region for people with TBI and depression, using transcranial magnetic stimulation (TMS). They enrolled 15 people in the pilot and saw success with the treatment. Since then, they have received funding to replicate the study in a multicenter military trial.

"We hope our discovery guides a precision medicineapproach to managing depression and mild TBI, and perhaps even intervene in neuro-vulnerable trauma survivors before the onset of chronic symptoms," said Rajendra Morey, MD, a professor of psychiatry at Duke University School of Medicine, and co-author on the study.

https://www.sciencedaily.com/releases/2023/07/230705142946.htm

Is TBI a chronic condition?

Study finds function may improve, decline up to seven years after injury

June 21, 2023

Science Daily/American Academy of Neurology

People with TBI may continue to improve or decline years after their injury, making it a more chronic illness, according to a study published in the June 21, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Our results dispute the notion that TBI is a one-time event with a stagnant outcome after a short period of recovery," said study author Benjamin L. Brett, PhD, of the Medical College of Wisconsin in Milwaukee. "Rather, people with TBI continue to show improvement and decline across a range of areas including their ability to function and their thinking skills."

The study involved people at 18 level 1 trauma center hospitals with an average age of 41. A total of 917 people had mild TBI and 193 people had moderate to severe TBI. They were matched to 154 people with orthopedic injuries but no head injuries. Participants were followed for up to seven years.

Participants took three tests on thinking, memory, mental health and ability to function with daily activities annually from two to seven years post-injury. They also completed an interview on their abilities and symptoms, including headache, fatigue, and sleep disturbances.

When researchers looked at all test scores combined, 21% of people with mild TBI experienced decline, compared to 26% of people with moderate to severe TBI and 15% of people with orthopedic injuries with no head injury.

Among the three tests, researchers saw the most decline over the years in the ability to function with daily activities. On average, over the course of 2 to 7 years post-injury, a total of 29% of those with mild TBI declined in their abilities and 23% of those with moderate to severe TBI.

Yet some people showed improvement in the same area, with 22% of those with mild TBI improving over time and 36% of those with moderate to severe TBI.

"These findings point out the need to recognize TBI as a chronic condition in order to establish adequate care that supports the evolving needs of people with this condition," Brett said. "This type of care should place a greater emphasis on helping people who have shown improvement continue to improve and implementing greater levels of support for those who have shown decline."

A limitation of the study was that all participants were seen at a level 1 trauma center hospital within 24 hours of their injury, so the findings may not apply to other populations.

The study was funded by the National Institute of Neurological Disorders and Stroke, National Institute on Aging, the National Football League Scientific Advisory Board and the U.S. Department of Defense.

https://www.sciencedaily.com/releases/2023/06/230621164720.htm

Sports concussions increase injury risk

June 16, 2023

Science Daily/University of South Australia

Concussions are an unfortunate reality of contact sports at junior and senior levels. Now, sports experts at the University of South Australia are suggesting extended recovery times may be needed for youth athletes suffering from head trauma as new research shows a concussion can increase future injury risk by 50%.

Published in the Journal of Science and Medicine in Sport,the world-first study tracked and evaluated the long-term impact of concussion and subsequent injury risk of 1455 sub-elite junior Australian rules football players.

This builds on previous UniSA research that found an approximate 1.5-fold increased risk of injury of sub-elite Australian rules football players returning from an injury, compared to those with no injury.

Tracking injuries over a seven-season period, researchers found that football players who suffered a concussion were also about 1.5 times more likely to be reinjured in the future when compared to players who had never been injured. This increased risk was the same as players returning from upper and lower limb injuries.

The finding comes ahead of the Australian Senate's report into concussion injuries, and follows the AFL's announcement for a $25 million study into the long-term effects of concussions and head knocks.

In the AFL, concussions are one of the most common injuries, with an average of six concussions every 1000 hours played, which involve around 70 to 80 male players every year.

In junior elite football as well as AFL and AFLW, the guidelines for concussion say that the earliest a player can return to play post-concussion is 12 days after the injury, after following the graded progression through a return-to-play program.

Lead researcher, UniSA's Dr Hunter Bennett, says the significant and elevated risk of injury after a concussion may suggest a longer recovery time is required for some players to better recover before returning to play.

"The current recommendation of 12 days post-concussion may not be sufficient to allow full recovery in elite under-18 footballers," Dr Bennett says.

It may also indicate that the physical qualities impacted by concussion should be assessed more thoroughly before an athlete is cleared to return to the sport.

"Concussion is a common injury in Australian rules football that can lead to impairments in balance, coordination, reaction time, and decision making -- and these impairments can increase the risk of other injuries if an athlete returns to play before being fully recovered."

A recent consensus statement on concussion in sport also indicates that children and teenagers may take up to four-weeks to recover from a sport related concussion.

"Concussions are a unique injury that occur without muscle tissue damage, instead impacting aspects of motor control," Dr Bennett says.

"Recurrent injuries can significantly impact team success, player health, and career longevity.

"In elite sports, there is the potential for young athletes to overplay their readiness to return to sport after an injury, as they worry that missing games can exclude them from senior drafting or competition.

"When we know that athletes have a greater risk of another injury post a concussion, it suggests we need unique and careful rehabilitation strategies to monitor when an athlete is fully recovered and ready to return to play."

Researchers say that future research should seek to identify optimal rehabilitation and injury prevention strategies for athletes who suffer from concussions.

https://www.sciencedaily.com/releases/2023/06/230616161943.htm

Researchers comprehensively assess the safety of using your head in youth soccer

May 24, 2023

Science Daily/Children's Hospital of Philadelphia

Repeatedly heading a soccer ball has been previously associated with negative long-term brain health for professional players. However, in a new study from researchers at the Minds Matter Concussion Program at Children's Hospital of Philadelphia (CHOP), a small number of repeated soccer headers equivalent to a throw-in did not cause immediate neurophysiological deficits for teens, suggesting that limited soccer heading exposure in youth sports may not result in irreversible harm if players are properly trained.

The findings, which represent the most comprehensive real-time study of soccer headers in adolescent athletes, were published in the Journal of Biomechanical Engineering.

For some professional athletes, repeated head loading in sports -- using your head as part of the game -- is associated with negative long-term brain health even when there are no initial clinical symptoms. Despite the awareness of long-term consequences, short-term neurophysiological issues after repeated head impacts like soccer heading are poorly understood in youth athletes. Some studies have identified potential issues across an entire sports season. This study examined the consequences of repeated head impacts shortly after the heading exposure with a battery of six different tests to examine a wider variety of potential clinical implications.

In 2015, the US Soccer Federation implemented limits on soccer headers for teens during practice -- no more than 30 minutes of header practice time and no more than 15 to 20 headers per week. The English Premier League also passed guidelines restricting the number of high-force headers to 10 in a single practice per week. This lab-based study simulated these limits conducting 10 repeated soccer headers within a single session with experienced teenage players. Based on their findings, researchers determined that this practice did not result in acute neurophysiological issues, as assessed by a comprehensive exam. The study did not assess the safety of regular soccer headers over the course of a season or scholastic career.

"Soccer is a sport where intentionally using your head to hit the ball is an integral part of the game, and concern over its long-term effects has parents, caregivers and coaches understandably concerned," said first study author Colin Huber, PhD, a postdoctoral research fellow at Emory University who conducted this research while with the Center for Injury Research and Prevention (CIRP) at CHOP. "We wanted to simulate these effects in a controlled laboratory setting and build upon the work of prior studies to quantitatively assess the neurophysiological effects of repeated soccer heading."

In this study, 19 participants (17 male, 2 female) between 13 and 18 years old were assigned to either a frontal heading group (directing the ball back to where it came from), an oblique heading group (directing the ball to the right) or a kicking control group. These participants completed neurophysiological assessments immediately prior to, immediately after and approximately 24 hours after completing 10 headers or kicks. These assessments included multiple eye movement tracking, pupil response and balance tests.

The study ultimately found no neurophysiological issues in either group when compared with the kicking control group, even when taking the six different assessments into account. However, oblique headers resulted in higher levels of angular head motion. Angular motion is associated with concussions and other brain injuries, suggesting that players should be properly trained to head the ball in a frontal fashion to reduce the risk of injury.

"This study represents the most comprehensive examination of the acute neurophysiological effects of soccer headers on youth to date, providing us with meaningful information regarding the safety of headers on the field," said senior study author Kristy Arbogast, PhD, Co-Scientific Director at CIRP and research director of the Minds Matter Concussion Program at CHOP. "We need to be clear that there still may be long-term consequences for repeated soccer headers over the course of an athletic career, but it appears that a small number of headers in a given session does not pose an immediate risk to properly trained youth athletes."

This study was supported by the National Institute of Neurologic Disorders and Stroke of the National Institutes of Health grant R01NS097549 and internal funds from CHOP.

https://www.sciencedaily.com/releases/2023/05/230524181945.htm

Almost half of people with concussion still show symptoms of brain injury six months later

April 25, 2023

Science Daily/University of Cambridge

Even mild concussion can cause long-lasting effects to the brain, according to researchers at the University of Cambridge. Using data from a Europe-wide study, the team has shown that for almost a half of all people who receive a knock to the head, there are changes in how regions of the brain communicate with each other, potentially causing long term symptoms such as fatigue and cognitive impairment.

Mild traumatic brain injury -- concussion -- results from a blow or jolt to the head. It can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite being labelled 'mild', it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.

While some clinicians in recent studies predict that nine out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.

Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive a brain scan -- either a CT scan or an MRI scan, both of which look for structural problems, such as inflammation or bruising -- yet even if these scans show no obvious structural damage, a patient's symptoms may still persist.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the University of Cambridge said: "Worldwide, we're seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.

"At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms."

Dr Stamatakis and colleagues studied fMRI brain scans -- that is, functional MRI scans, which look at how different areas of the brain coordinate with each other -- taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.

The patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury, co-chaired by Professor David Menon (head of the division of Anaesthesia) and funded by the European Union.

In results published today in Brain, the team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.

The researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain -- in other words, the thalamus was trying to communicate more as a result of the injury -- and the greater this connectivity, the poorer the prognosis for the patient.

Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: "Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus -- the brain's relay system -- was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience."

By studying additional data from positron emission tomography (PET) scans, which can measure regional chemical composition of body tissues, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.

Dr Stamatakis, who is also Stephen Erskine Fellow at Queens' College, Cambridge, added: "We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient's prognosis, but we may also be able to offer a treatment targeting their particular symptoms."

https://www.sciencedaily.com/releases/2023/04/230425205339.htm

Age of first exposure to tackle football and years played associated with less white matter in brain

New finding suggests that future therapies should target white matter loss in former contact sport athletes

March 6, 2023

Science Daily/Boston University School of Medicine

Chronic traumatic encephalopathy (CTE) is not the only problem football players should be aware of. Long careers in American football are linked to less white matter in the brain and associated with problems with impulsive behavior and thinking according to a new study from the Boston University CTE Center. This finding is independent of whether football players had chronic traumatic encephalopathy (CTE).

CTE is a progressive neurodegenerative disease frequently found in contact sports athletes. However, many former contact sports athletes suffer from thinking problems and impulsive behavior in the absence of CTE, or with very mild CTE. This new study suggests that a separate type of brain damage, which can appear earlier than CTE, may underlie some of these symptoms.

"Damage to the white matter may help explain why football players appear more likely to develop cognitive and behavioral problems later in life, even in the absence of CTE," said corresponding author Thor Stein, MD, PhD, a neuropathologist at VA Boston Healthcare System and assistant professor of pathology and laboratory medicine at Boston University Chobanian & Avedisian School of Medicine.

The researchers studied the brains of 205 deceased American football players donated to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank and measured levels of myelin, a component of white matter that covers, protects and speeds up the connections in the brain. They then interviewed family members on measures of cognition and impulsivity and then compared how career length and age of beginning tackle football related to levels of myelin, and how myelin levels related to cognition and impulsivity. In addition to more years of football played, the researchers found that starting tackle football at a younger age was also related to more white matter loss, independent of career length.

"These results suggest that existing tests that measure white matter injury during life, including imaging and blood tests, may help to clarify potential causes of changes in behavior and cognition in former contact sport athletes. We can also use these tests to better understand how repeated hits to the head from football and other sports lead to long term injury to the white matter," said co-author Michael L. Alosco, PhD, associate professor of neurology.

The researchers hope these findings help reinforce the idea that more needs to be done to protect the brains of athletes, especially children, from repeated hits to the head.

These finding appear online in the journal Brain Communications.

This work was supported by grant funding from: NIA (AG057902, AG06234, RF1AG054156), NINDS (U54NS115266, K23NS102399, RF1NS122854), National Institute of Aging Boston University AD Center (P30AG072978); the United States Department of Veterans Affairs, Veterans Health Administration, BLRD Merit Award (I01BX005161); the Nick and Lynn Buoniconti Foundation, and BU-CTSI Grant Number 1UL1TR001430. The views, opinions and/or findings contained in this article are those of the authors and should not be construed as an official Veterans Affairs or Department of Defense position, policy or decision, unless so designated by other official documentation. Funders did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

https://www.sciencedaily.com/releases/2023/03/230306143450.htm

Lending a paw for defense veterans: 'Clear evidence' that assistance dogs help improve mental health

March 1, 2023

Science Daily/University of South Australia

A new Australian study focused on defence veterans' mental health has found strong evidence that assistance dogs used in conjunction with traditional therapies provide the most effective treatment outcomes.

Almost 90 per cent of veterans reported improvements in their post-traumatic stress, depression and anxiety 12 months after being matched to an assistance dog, according to researchers from the University of South Australia (UniSA), University of Adelaide, and Military and Emergency Services Health Australia (MESHA).

Of the 16 returned veterans who took part in the study, 63 per cent reported "significant clinical improvements" to their mental health thanks to an assistance dog provided by the Operation K9 Program run by See Differently with the Royal Society for the Blind.

The study, funded by The Hospital Research Foundation Group, is the first in Australia to use self-reported measures, clinical assessments, and face-to-face interviews with veterans to investigate the value of an assistance dog over time.

It is published in the International Journal of Environmental Research and Public Health.

UniSA Master of Clinical Psychology student Melissa Sherman, who analysed the data, says the findings are relevant to policymakers and demonstrate the power of human-animal relationships.

"Previous studies have shown that existing treatments for post-traumatic stress among returned veterans are not ideal, with high dropout rates and poor adherence," Sherman says.

"This study provides clear evidence that assistance dogs can play a key role in a veteran's recovery from post-traumatic stress and other mental health conditions, supporting existing treatments."

Of the 5000 ADF members who transition from the forces to civilian life every year, 46 per cent experience mental health issues, including suicidal thoughts, anxiety, and depression. Almost a quarter of them are diagnosed with post-traumatic stress in their lifetime.

"This is an important issue that needs addressing," according to MESHA Executive Director Miranda Van Hooff, an Adjunct Associate Professor at both UniSA and the University of Adelaide.

Three major themes emerged from the study: that assistance dogs were a "life changer," a constant companion, and helped returned veterans to increase their social interactions.

"For many veterans, an assistance dog gave them a sense of purpose and a reason to live," Assoc Prof Van Hooff says.

Veterans reported their dog helped them "reclaim their life," giving them independence and a way to manage their mental health issues and fluctuating emotions, including hypervigilance.

Some participants described their dog as "a comfort or security blanket," with one veteran saying he was a recluse for many years until being matched with an assistance dog: 'Now, every day is an adventure, giving me something to look forward to'.

The study showed a slight drop in participants still reporting suicidal feelings after 12 months, but the reduction was not significant. The main benefits were a large reduction in depression, anxiety, and post-traumatic stress symptoms.

Researchers say the study was limited by the lack of a control group of veterans with post-traumatic stress not receiving an assistance dog, and the small number of study participants due to the cost of breeding, training, and matching dogs to veterans.

https://www.sciencedaily.com/releases/2023/03/230301101544.htm

Head injury is associated with doubled mortality rate long-term

More severe head injuries increased mortality rates in the 30-year study period

January 24, 2023

Science Daily/University of Pennsylvania School of Medicine

Adults who suffered any head injury during a 30-year study period had two times the rate of mortality than those who did not have any head injury, and mortality rates among those with moderate or severe head injuries were nearly three times higher, according to new research from the Perelman School of Medicine at the University of Pennsylvania, published today in JAMA Neurology.

In the United States, over 23 million adults age 40 or older report a history of head injury with loss of consciousness. Head injury can be attributed to a number of causes, from motor vehicle crashes, unintentional falls, or sports injuries. What's more, head injury has been linked with a number of long-term health conditions, including disability, late-onset epilepsy, dementia, and stroke.

Studies have previously shown increased short-term mortality associated with head injuries primarily among hospitalized patients. This longitudinal study evaluated 30 years of data from over 13,000 community-dwelling participants (those not hospitalized or living in nursing home facilities) to determine if head injury has an impact on mortality rates in adults over the long term. Investigators found that 18.4 percent of the participants reported one or more head injuries during the study period, and of those who suffered a head injury, 12.4 percent were recorded as moderate or severe. The median period of time between a head injury and death was 4.7 years.

Death from all causes was recorded in 64.6 percent of those individuals who suffered a head injury, and in 54.6 percent of those without any head injury. Accounting for participant characteristics, investigators found that the mortality rate from all-causes among participants with a head injury was 2.21 times the mortality rate among those with no head injury. Further, the mortality rate among those with more severe head injuries was 2.87 times the mortality rate among those with no head injury.

"Our data reveals that head injury is associated with increased mortality rates even long-term. This is particularly the case for individuals with multiple or severe head injuries," explained the study's lead author, Holly Elser, MD, PhD, MPH a Neurology resident at Penn. "This highlights the importance of safety measures, like wearing helmets and seatbelts, to prevent head injuries."

Investigators also evaluated the data for specific causes of death among all participants. Overall, the most common causes of death were cancers, cardiovascular disease, and neurologic disorders (which include dementia, epilepsy, and stroke). Among individuals with head injuries, deaths caused by neurologic disorders and unintentional injury or trauma (like falls) occurred more frequently.

When investigators evaluated specific neurologic causes of death among participants with head injury, they found that nearly two-thirds of neurologic causes of death were attributed to neurodegenerative diseases, like Alzheimer's and Parkinson's disease. These diseases composed a greater proportion of overall deaths among individuals with head injury (14.2 percent) versus those without (6.6 percent).

"Study data doesn't explain why the cause of death in individuals with head injuries is more likely to be from neurodegenerative diseases, which underscores the need for further research into the relationship between these disorders, head injury, and death," said Andrea L.C. Schneider, MD, PhD, an assistant professor of Neurology at Penn.

https://www.sciencedaily.com/releases/2023/01/230124192620.htm

Good news for athletes who are slow to recover from concussion

Most need just one more month to return to play

January 18, 2023

Science Daily/American Academy of Neurology

A new study suggests that athletes who recover more slowly from concussion may be able to return to play with an additional month of recovery beyond the typical recovery time, according to a new study published in the January 18, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. Slow recovery was defined as taking more than 14 days for symptoms to resolve or taking more than 24 days to return to play, both of which are considered the typical recovery times for about 80% of athletes with concussion.

"Although an athlete may experience a slow or delayed recovery, there is reason to believe recovery is achievable with additional time and injury management," said study author Thomas W. McAllister, MD, of the Indiana University School of Medicine in Indianapolis. "This is an encouraging message that may help to relieve some of the discouragement that athletes can feel when trying to return to their sport. While some athletes took longer than 24 days to return to play, we found that three-quarters of them were able to return to sports if given just one more month to recover."

The study looked at 1,751 college athletes who had been diagnosed with a concussion by a team physician. Of the athletes, 63% were male and 37% were female. Male athletes participated primarily in football, soccer and basketball. Female athletes participated primarily in soccer, volleyball and basketball.

Participants were evaluated five times: within six hours after their injury, one to two days later, once free of symptoms, once cleared to return to play and at six months.

Participants reported symptoms daily to medical staff, up to 14 days following injury and then weekly if they had not yet returned to play.

A total of 399 athletes, or 23%, had a slow recovery.

Researchers found that of the athletes who took longer than 24 days to return to play, more than three-fourths, or 78%, were able to return to play within 60 days of injury, and four-fifths, or 83%, were able to return to play within 90 days of injury. Only 11% had not returned to play six months after injury.

For the slow recovery group, the average time for returning to play was 35 days after injury, compared to 13 days in the overall group.

"The results of this study provide helpful information for athletes and medical teams to consider in evaluating expectations and making difficult decisions about medical disqualification and the value of continuing in their sport," McAllister said.

A limitation of the study is that participants were all collegiate varsity athletes and may not be representative of other age groups or levels of sport, and the results may not apply to other types of mild brain injuries.

https://www.sciencedaily.com/releases/2023/01/230118195719.htm

Treatment for combat-related PTSD advances with method shown to be fast, effective

January 5, 2023

Science Daily/University of Texas Health Science Center at San Antonio

Study findings out today in JAMA Network Open show an important step forward in treating the psychological injuries of war.

Researchers report that treatment for combat-related post-traumatic stress disorder (PTSD), which affects hundreds of thousands of U.S. military personnel and veterans, can be both fast and effective for a majority of patients. Their study showed clinically significant reductions in PTSD symptoms in more than 60 percent of patients and long-term remission of the diagnosis in more than 50 percent after three weeks of outpatient Prolonged Exposure therapy. Study participants similarly showed significant improvements in related disability and daily functioning.

Results were comparable whether patients received traditional Prolonged Exposure, also called PE, condensed into three weeks of daily treatment or an intensive outpatient format including several enhancements to address specific challenges of PTSD in war fighters.

The research team, led by Alan Peterson, PhD, of The University of Texas Health Science Center at San Antonio (UT Health San Antonio), conducted the randomized clinical trial with 234 military personnel and veterans recruited from four locations in South and Central Texas. The effort was part of the work of the Consortium to Alleviate PTSD (CAP), a national network jointly funded by the U.S. Departments of Defense and Veterans Affairs.

Dr. Peterson, professor of psychiatry and behavioral sciences at UT Health San Antonio and director of the CAP and the STRONG STAR Consortium, said the findings advance the group's previous research and significantly improve upon earlier outcomes.

Improving outcomes for our war fighters

"We're excited to see a more than 10-point increase in PTSD remission rates compared to a previous PE study we conducted, when we initiated the first ever clinical trials evaluating PTSD treatments in active-duty military populations," said Dr. Peterson.

That first study tested the standard PE protocol, with 10 sessions of 90 minutes each over the course of eight weeks, as well as a massed format, with daily 90-minute sessions over two weeks. The two delivery formats proved equally effective in reducing symptoms and leading to a loss of diagnosis, with remission rates under 50 percent initially after treatment, and treatment gains maintained by about 40 percent of patients six months later. The massed format had much lower dropout rates.

"Those initial results were encouraging, indicating that PE is effective for combat-related PTSD," said Dr. Peterson. "But with much lower success rates than in civilians treated with this therapy, we wanted to make and test treatment adaptations potentially to address unique aspects of combat-related PTSD and improve outcomes," he said. That is what the current study did.

Design and rationale of the current study

Prolonged Exposure includes patients' repeated retelling of their trauma stories along with homework assignments to engage in activities patients otherwise avoid because they trigger traumatic memories or anxious feelings. The goal is to help patients process thoughts about their trauma, calm the anxiety the memories provoke, and regain control of their lives.

It was thought that, in the original study -- particularly with the massed format -- patients may not have had adequate time to complete homework assignments and may also have faced a number of distractions. So, for both arms of the current study, patients took leave from work or other daily responsibilities to devote themselves full-time to treatment and recovery.

Also with the current study, treatment time in both arms was expanded from two weeks to three, with the consideration that combat-related PTSD is more difficult to treat, and patients may need additional time to process traumatic memories.

The comparison arm, called Massed-PE, had these treatment delivery changes only. The other arm, called Intensive Outpatient or IOP-PE, had several additional enhancements that researchers hypothesized would improve treatment outcomes with combat-related PTSD.

Dr. Peterson explained one example. "Oftentimes, a civilian trauma involves a one-time traumatic event, such as an accident, or a repeated trauma of a certain type, such as abuse," he said. "In the course of one or more combat deployments, service members may experience hundreds of traumatic events involving different types of traumas. They also may have experienced other types of trauma outside the combat environment. And so we wanted to adapt the traditional PE protocol, in which a patient focuses only on one primary trauma during treatment, and allow patients in this study to work with therapists on their three top traumas."

He said the treatment involved starting with the least distressing of those three traumas to gain confidence in the therapy, then working up to the most distressing trauma. Some of the other modifications included team-based treatment, with more than one clinician supporting a patient's care; clinic-based completion of homework assignments to decrease avoidance; brief therapist feedback sessions during the day for added support and increased opportunities for processing; involvement of a family member or friend during educational sessions to help improve social support; and post-treatment booster sessions to help maintain treatment gains.

Findings, implications and next steps

Outcomes differed from researchers' expectations in that both arms showed similar levels of reductions in PTSD symptoms and related disability, as well as similar increases in PTSD remission rates and improved psychosocial functioning over time. With some measures, Massed-PE led to greater improvements initially that decreased by the six-month follow-up. IOP-PE patients were more likely to maintain their improvements six months after treatment.

Since long-term outcomes did not differ significantly, researchers say the additional investment of resources needed for the IOP-PE format may not be warranted, but the overall study findings are highly positive.

"With about two thirds of participants reporting clinically meaningful symptom improvement and more than half losing their PTSD diagnosis, this study provides important new evidence that combat-related PTSD can be effectively treated -- in as little as three weeks," said Dr. Peterson.

He and his colleagues stated that, while condensed treatments may not be feasible for everyone, "results show that compressed formats adapted to the military context resulted in significant, meaningful and lasting improvements in PTSD, disability and functional impairments for most participants."

They say this makes condensed treatments an important option for U.S. service members and veterans after two decades of military operations in Iraq and Afghanistan. These treatments also could gain attention now as the war in Ukraine has raised international concerns about the risk of PTSD in military personnel and civilians.

Moving forward, the study team notes that their findings show room for continued improvement in treating combat-related PTSD. They add that the compressed treatment formats evaluated in this study are well suited for the evaluation of new, alternative modes of therapy combining cognitive-behavioral treatments with medications and medical devices. "We have those types of studies already underway," said Dr. Peterson.

https://www.sciencedaily.com/releases/2023/01/230105151330.htm

Blood pressure drug holds promise for treating PTSD

January 5, 2023

Science Daily/Medical College of Georgia at Augusta University

There is new evidence that a 50-year-old blood pressure drug could find new purpose as a treatment to mitigate the often life-altering effects of increasingly prevalent PTSD, scientists say.

Clonidine is commonly used as a high blood pressure medication and for ADHD. It's also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in "fight or flight," a heightened state of response that helps keep us safe. These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory. Clonidine's sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.

Scientists at the Medical College of Georgia at Augusta University say it's time for another look at clonidine.

They have laboratory evidence that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer's Therapeutics Discovery at MCG.

Their results published in the journal Molecular Psychiatry suggest that clonidine could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.

Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.

The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.

In the hippocampus, the center of learning and memory, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories in which you associate a place or situation, like the site of a horrific car accident or school shooting, with fear or other distressing emotions that are hallmarks of PTSD.

In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.

A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.

"Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger," Wang says, morphing from a slender profile to a more mushroom-like shape.

"The mushroom spine is very important for your memory formation," says corresponding author Wang, Georgia Research Alliance Eminent Scholar in Neuropharmacology. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.

The scientists found clonidine interferes with cofilin's exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine's ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.

The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating -- and so sustaining -- a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.

There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier. Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behavior.

Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.

"The interpretation is that they don't have as strong a memory," she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier's life.

When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilizes, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.

Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.

Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.

Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.

PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be "profound."

Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, which include only two drugs which have Food and Drug Administration approval specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.

Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.

The U.S. Department of Veterans Affairs defines post-traumatic stress disorder as a mental health problem that some people develop after experiencing or witnessing a life-threatening or traumatic event. While problems like feeling on edge, trouble sleeping and/or nightmares may last a few weeks or more after the event, if symptoms like these as well as flashbacks and increasingly negative thoughts continue, it's likely PTSD. Sometimes symptoms don't surface until months after the initial event.

https://www.sciencedaily.com/releases/2023/01/230105083101.htm

Morning blue light treatment improves sleep in patients with PTSD

November 1, 2022

Science Daily/University of Arizona Health Sciences

People with post-traumatic stress disorder (PTSD) experienced better sleep, a reduction in the severity of PTSD symptoms and more effective treatments after exposure to blue light therapy, according to a new study conducted by researchers in the University of Arizona College of Medicine -- Tucson's Department of Psychiatry and recently published in Frontiers in Behavioral Neuroscience.

Sleep is crucial for maintaining physical and mental health, and inadequate sleep over time can impact all aspects of life with serious implications for long-term health, relationships, cognitive abilities such as learning, and healing.

The influence of sleep disruption on PTSD symptom severity is well established. Those who seek treatment to allay their PTSD symptoms often face a vicious cycle where poor sleep interferes with the effectiveness of treatments, negating any lessening of symptoms, which in turn contributes to sleep disruptions. To reduce and eliminate the emotional impact of traumatic memories, the patient needs quality sleep to integrate healing mechanisms achieved through cognitive or exposure therapy treatments.

"This research is exciting and unique because it points to an easy-to-use method for helping those with PTSD to retain the benefits of therapy long after the treatment ends," said psychiatry professor William "Scott" Killgore, PhD, director of the Social, Cognitive and Affective Neuroscience (SCAN) Lab and senior author on the paper, "Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder."

Dr. Killgore and the SCAN Lab team conducted a comprehensive assessment of daily morning blue-wavelength light exposure on individuals with clinically significant levels of PTSD. The goal was to ascertain if blue light therapy would help improve sleep and PTSD symptoms and sustain learned fear extinction memories, an analog of therapeutic treatment for trauma.

Study participants committed to 30 minutes of morning light exposure daily for six weeks, with half of the participants using blue-wavelength light and half using amber light. Researchers examined the neurobiological, autonomic and behavioral outcome changes during the study.

The 43 participants who received blue light therapy not only demonstrated significant improvements in the severity of their PTSD symptoms, but also reported improvements in sleep and showed an increased retention of fear extinction memories. In comparison, the 39 study participants who received amber light did not show the same retention of the extinction memories, but rather showed a return of the original fear memories.

"While the limitations of the research include its modest sample size and difficulties monitoring compliance, the possibilities of utilizing a treatment that is relatively simple, drug-free and inexpensive can offer hope for the large population of people living with the intense challenges of post-traumatic stress disorder," Dr. Killgore said.

"The data are thrilling," said Jordan Karp, MD, professor and chair of the College of Medicine -- Tucson's Department of Psychiatry. "This nonpharmacological intervention is a promising life-changing and life-saving possibility for people suffering from PTSD."

https://www.sciencedaily.com/releases/2022/11/221101195628.htm

New clues into how the circadian clock helps the brain recover after injury

September 19, 2022

Science Daily Children's National Hospital

A type of brain cell that can renew itself is regulated by circadian rhythms, providing significant insights into how the body's internal clock may promote healing after traumatic brain injuries (TBI), according to new research from Children's National Hospital.

Released in the latest issue of eNeuro, the findings open new avenues of investigation for future TBI therapies. These injuries are currently managed only with supportive care and rehabilitation, rather than targeted drug treatment options. The findings also underscore the importance of addressing circadian disturbances to help injured brains heal.

Many of the body's cells follow a 24-hour rhythm driven by their genes known as the circadian clock. The Children's National research team found that a relatively newly discovered type of brain cell - known as NG2-glia, or oligodendrocyte precursor cells - also follow a circadian rhythm. This cell type is one of the few that continually self-renews throughout adulthood and is notably proliferative in the first week after brain injuries.

"We have found evidence for the role of this well-known molecular pathway -- the molecular circadian clock -- in regulating the ability for these NG2-glia to proliferate, both at rest and after injury," said Terry Dean, M.D., Ph.D., critical care specialist at Children's National and the lead author of the paper. "This will serve as a starting point to further investigate the pathways to controlling cellular regeneration and optimize recovery after injury."

Sometimes called "the silent epidemic," TBI afflicts an estimated 69 million people worldwide each year, with injuries ranging from mild concussions to severe injuries that cause mortality or lifelong disability. In the United States alone, approximately 2.8 million people sustain TBI annually, including 630,000 children. TBI is the leading cause of death in people under age 45, and those who survive are often left with persistent physical, cognitive and psychological disabilities.

Yet no targeted therapies exist for TBI, creating a critical need to uncover the mechanisms that could unlock the regeneration of these NG2-glia cells, which are the most common type of brain cell known to proliferate and self-renew in adult brains.

"It is essential for researchers to know that cell renewal is coordinated with the time of day," said Vittorio Gallo, Ph.D., interim chief academic officer and interim director of the Children's National Research Institute. "With this knowledge, we can dig deeper into the body's genetic healing process to understand how cells regulate and regenerate themselves."

https://www.sciencedaily.com/releases/2022/09/220919144017.htm

Mind over matter: Helping amputees regain their independence

September 15, 2022

Science Daily University of Nevada, Las Vegas

New research says adopting a new, attentional mindset in the field of physical therapy can help amputees live with prosthesis more naturally.

There are more than two million people living with an amputation in the United States, with about 400 being added daily. For many of them, prostheses or artificial limbs are a part of their lives, and they need to relearn how their bodies move with their new limbs all over again.

The trick to learning how to use a new limb -- and regaining confidence in movement -- has less to do with the prosthesis itself and more to do with the mind, according to newly published research by UNLV physical therapy researcher Szu-Ping Lee. By adopting the right attentional focus during rehab, patients can learn new skills better and faster.

"Vascular diseases and diabetes are becoming more common and one of the long-term consequences is amputation," said Lee. "It is important that clinicians like prosthetists and physical therapists apply the newest science so that their patients can learn faster and retain the skills that they learned better."

The current standard of practice in rehabilitating the millions of amputees in the country prioritizes internally focused instructions where the patients are told to move their joints or contract their muscles in certain ways, which is a suboptimal mindset that Lee says we should think about changing. And the science is grounded in sports kinesiology research built by fellow UNLV professor Gabriele Wulf.

Let's go golfing for a better understanding:

After approaching the ball and reading the green, you square your shoulders -- lining up the putt. At this point, most of us are concentrating on our form and measuring every muscle movement like a pseudo-pro. This is the standard process for rehab, internal focus.

But there's another path forward. Instead of prioritizing our body movement, focusing on the path of the ball or simply the hole is more intuitive and works better. This is what Wulf and Lee are talking about -- the focus is on the outcome, not the movement itself.

Professor Wulf's research over the last 20 years has shown that external-focus for motor tasks leads to faster learning and improved movement effectiveness and neuromuscular efficiency. Lee is hoping that this technique can help amputees more quickly master the use of artificial limbs.

"With the wrong kind of focus or instruction being used during physical therapy, the consequences can be catastrophic-the artificial leg becomes a paperweight in a closet," said Lee. "We want to advance clinical practice and that's the ultimate goal. We want physical therapy to get better and better for the patients."

The lower-limb prosthesis rehabilitation of 21 adults was monitored for this research, along with the verbal instructions provided. Results showed that most of the verbal interactions were internally-focused (standard) on patients' body movements and not externally on the movement effects. More research is being done to evaluate how motor learning outcomes such as balance and fall prevention may be improved with better instructions.

https://www.sciencedaily.com/releases/2022/09/220915123621.htm

Mild traumatic brain injury increases risk of behavioral and emotional problems in kids

September 13, 2022

Science Daily University of Rochester Medical Center

University of Rochester researchers have been at the forefront of efforts to understand how blows to the head impact the brain, including how concussions change brain structure . Now researchers at the Del Monte Institute for Neuroscience have found that kids who experience a traumatic brain injury (TBI), even a mild one, have more emotional and behavioral problems than kids who do not.

"These hits to the head are hard to study because much of it depends on recall of an injury since the impacts do not all require a visit to a doctor," said Daniel Lopez, a Ph.D. candidate in the Epidemiology program and first author of the study out today in NeuroImage. "But being able to analyze longitudinal data from a large cohort and ask important questions like this gives us valuable information into how a TBI, even a mild one, impacts a developing brain."

Researchers used MRI and behavioral data collected from thousands of children who participated in the Adolescence Brain Cognitive Development (ABCD) Study. They revealed children with a mild TBI experienced a 15-percent increased risk of an emotional or behavioral problem. The risk was the highest in children around ten years old. Researchers found that children who had a significant hit to the head but did not meet diagnostic criteria for a mild TBI also had an increased risk of these behavioral and emotional problems.

The University of Rochester Medical Center is one of 21 research sites collecting data for the National Institutes of Health ABCD Study. Since 2017, 340 children from the greater Rochester area have been part of the 10-year study that is following 11,750 children through early adulthood. It looks at how biological development, behaviors, and experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, and overall health.

Researchers hope future ABCD Study data will better reveal the impact these head hits have on mental health and psychiatric problems. "We know some of the brain regions associated with increased risk of mental health problems are impacted during a TBI," said Ed Freedman, Ph.D., associate professor of Neuroscience and co-principal investigator of the ABCD Study at the University of Rochester. Freedman also led this study. "With more time and data, we hope to gain a better understanding of the long-term impact of even a mild TBI."

https://www.sciencedaily.com/releases/2022/09/220913183124.htm

Your blood type could predict your risk of having a stroke before age 60

Research could lead to potential new ways to predict and prevent strokes in young adults

August 31, 2022

Science Daily/University of Maryland School of Medicine

A person's blood type may be linked to their risk of having an early stroke, according to a new meta-analysis led by University of Maryland School of Medicine (UMSOM) researchers. Findings were published today in the journal Neurology. The meta-analysis included all available data from genetic studies focusing on ischemic strokes, which are caused by a blockage of blood flow to the brain, occurring in younger adults under age 60.

"The number of people with early strokes is rising. These people are more likely to die from the life-threatening event, and survivors potentially face decades with disability. Despite this, there is little research on the causes of early strokes," said study co-principal investigator Steven J. Kittner, MD, MPH, Professor of Neurology at UMSOM and a neurologist with the University of Maryland Medical Center.

He and his colleagues conducted the study by performing a meta-analysis of 48 studies on genetics and ischemic stroke that included 17,000 stroke patients and nearly 600,000 healthy controls who never had experienced a stroke. They then looked across all collected chromosomes to identify genetic variants associated with a stroke and found a link between early-onset stroke -- occurring before age 60 -- and the area of the chromosome that includes the gene that determines whether a blood type is A, AB, B, or O.

The study found that people with early stroke were more likely to have blood type A and less likely to have blood type O (the most common blood type) -- compared to people with late stroke and people who never had a stroke. Both early and late stroke were also more likely to have blood type B compared to controls. After adjusting for sex and other factors, researchers found those who had blood type A had a 16 percent higher risk of having an early stroke than people with other blood types. Those who had blood type O had a 12 percent lower risk of having a stroke than people with other blood types.

"Our meta-analysis looked at people's genetic profiles and found associations between blood type and risk of early-onset stroke. The association of blood type with later-onset stroke was much weaker than what we found with early stroke," said study co-principal investigator Braxton D. Mitchell, PhD, MPH, Professor of Medicine at UMSOM.

The researchers emphasized that the increased risk was very modest and that those with type A blood should not worry about having an early-onset stroke or engage in extra screening or medical testing based on this finding.

"We still don't know why blood type A would confer a higher risk, but it likely has something to do with blood-clotting factors like platelets and cells that line the blood vessels as well as other circulating proteins, all of which play a role in the development of blood clots," said Dr. Kittner. Previous studies suggest that those with an A blood type have a slightly higher risk of developing blood clots in the legs known as deep vein thrombosis. "We clearly need more follow-up studies to clarify the mechanisms of increased stroke risk,"he added.

In addition to Dr. Kittner and Dr. Mitchell, UMSOM faculty involved in this study included Huichun Xu, MD, PhD, Associate Professor of Medicine; Patrick F. McArdle, PhD, Associate Professor of Medicine; Timothy O'Connor, PhD, Associate Professor of Medicine; James A. Perry, PhD, Assistant Professor of Medicine; Kathleen A. Ryan, MPH, MS, Statistician; John W. Cole, MD, Professor of Neurology; Marc C. Hochberg, MD, MPH, Professor of Medicine; O. Colin Stine, PhD, Professor of Epidemiology and Public Health; and Charles C. Hong, MD, PhD, Melvin Sharoky MD Professor of Medicine.

A limitation of the study was the relative lack of diversity among participants. The data was derived from the Early Onset Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. About 35 percent of the participants were of non-European ancestry.

"This study raises an important question that requires a deeper investigation into how our genetically predetermined blood type may play a role in early stroke risk," said Mark T. Gladwin, MD, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "It points to the urgent need to find new ways to prevent these potentially devastating events in younger adults."

The study was supported by the National Institutes of Health and Department of Veterans Affairs. Researchers from more than 50 institutions worldwide were co-authors on this study.

https://www.sciencedaily.com/releases/2022/08/220831162509.htm

Study with military suggests 'blended' individual and team mindfulness is at least as effective as standard mindfulness training

Team mindfulness training combining collective stress management skills with elements of the individually-focused mindfulness-based stress reduction (MBSR) course could offer more benefit than MBSR alone, study suggests.

August 23, 2022

Science Daily/City University London

A new study suggests that a 'blended' eight-week mindfulness programme that adds Team Mindfulness Training (TMT) to a shortened version of the mindfulness-based stress reduction (MBSR) course for individual mindfulness is just as effective as the standard MBSR course alone. It may even offer further benefit by increasing collective stress management skills.

Led by Dr Jutta Tobias Mortlock, Co-director of the Centre for Excellence in Mindfulness Research (CEMR) at City, University of London, in collaboration with Dr Alison Carter, Principal Research Fellow at the Institute of Employment Studies (IES), the study bridges the gap between the well-established body of research supporting the benefits of individual mindfulness practice, epitomised by the eight-week MBSR course, and the burgeoning science on team and collective mindfulness. MBSR has been shown to reduce stress, anxiety, depression, and pain. Collective mindfulness is strongly linked to organisational resilience.

The study was conducted in a high-stress military context: military officers in training in the British Army and in the Royal Navy, and was funded by the Defence Science and Technology Laboratory (DSTL). A mixed method approach was used that consisted of two research phases.

Twenty-three junior officers-to-be from the British Army participated in a pre-pilot study which trialled the newly designed Team Mindfulness Training (TMT) intervention: half the time was dedicated to training participants in individual stress management skills using the MBSR curriculum, with the remainder focusing on training collective stress management skills using the principles of collective mindfulness.

A larger pilot study, in which 105 Royal Navy officer cadets took part, then compared the TMT intervention against the standard eight-week MBSR course. The effect of participating in either intervention group was measured by assessing individual resilience, collective mindfulness, and individual performance. While the two former measures were self-reported, the last was assessed using an objective computer-test of working memory, as a proxy for performance at work. All measures were taken at three time points: directly before, directly after and two months after the intervention. Participants also took part in semi-structured interviews.

The study found that participating in both intervention groups led to significantly increased individual resilience and working memory, with no significant difference between the two groups.

Whilst neither group showed statistically significant improvements in collective mindfulness over time, the TMT group experienced a near-significant collective mindfulness increase after participating in the training.

In addition, results from analyses of the interviews suggest that participants in the TMT group seem more able to report that they had learned to manage difficult work stress collectively. Most notably, however, only individuals from the TMT group (and none from the MBSR group) indicated they were able to apply their newly learned MBSR skills to stressful work challenges. This suggests that a collectively mindful team atmosphere supported the application of individual stress management skills when it really mattered.

The authors suggest that the study opens up ground for follow-up research that may help address recently reported counterintuitive effects of individually-focused workplace mindfulness, such as lower work motivation after brief periods of mindful meditation.

They also stress that this study brings back the prosocial orientation to mindfulness practice that may have been eclipsed by the more recent mindfulness-as-self-help movement. This prosocial aspiration is a core tenet of mindfulness traditions: to generate transformative capacity to overcome stress and suffering in oneself as well as for all.

First author of the study, Dr Jutta Tobias Mortlock, says:

Our intervention considers mindfulness as a team sport. Combining individual with collective mindfulness makes mindfulness training more powerful. And offering mindfulness practices to organisations that stretch beyond individually-focused meditation helps extend the transformative potential of mindfulness for organisations.

Dr Alison Carter, Principal Investigator of the study and co-author of its publication, adds:

This work shifts the needle from self-focused mindfulness towards creating a mindful culture in workplaces. This is both helpful and practical because when people at work look out for each other, then stress at work becomes a collective responsibility rather than something that needs to be shouldered by individuals in isolation of others. And we know that managing stress collectively is more effective than managing stress alone.

https://www.sciencedaily.com/releases/2022/08/220823095440.htm

Hepatitis C drugs may reduce PTSD symptoms

August 22, 2022

Science Daily/Boston University School of Public Health

More than six percent of Americans will develop posttraumatic stress disorder (PTSD) in their lifetime. This potentially chronic condition disrupts lives, and can lead to or exacerbate existing health issues such as depression, anxiety, eating disorders, and suicidal thoughts.

Despite the high prevalence of PTSD, the US Food and Drug Administration has only approved two medications to treat this condition -- sertraline and paroxetine -- and both have shown only limited effectiveness in reducing PTSD symptoms.

PTSD is also common among military veterans; more than 10 percent of US Department of Veterans Affairs (VA) patients experience these symptoms. Two years ago, researchers at Boston University School of Public Health (BUSPH) and the White River Junction Veterans Affairs Medical Center in Vermont began to investigate whether existing medications may improve PTSD symptoms, with funding from the National Institute of Mental Health.

During an initial exploratory analysis among a national cohort of VA patients, the researchers unexpectedly found that several new direct acting antiviral (DAA) medications used to treat hepatitis C virus infection were associated with PTSD symptom improvement. The findings were published in the journal Biological Psychiatry.

Now, in a new, follow-up study, the researchers have conducted a more rigorous analysis to examine and compare the effectiveness of the previously identified DAAs in PTSD symptom improvement. Their new analysis suggests the most promising DAA for prospective study as a potential medication for PTSD in patients without hepatitis C virus infection.

Published online ahead of print in the American Journal of Epidemiology, the new study found that the medication combination glecaprevir and pibrentasvir had the strongest association with PTSD symptom improvement among the DAAs most prescribed in the VA.

"Many people have PTSD, but there few effective pharmacologic treatments and limited drug development for PTSD," says co-principal investigator and study senior author Jaimie Gradus, associate professor of epidemiology at BUSPH. "Existing effective treatments are mostly psychotherapy, and while they work well, there are also issues with them, including a lot of treatment drop-out and they're time-intensive, so adding to the suite of treatment options for people is a high priority."

The researchers examined the same national cohort of VA patients as the prior study, but narrowed the study group to include only patients diagnosed with hepatitis C.

"There really has been a lot of interest in finding new medications for PTSD in the field," says co-principal investigator Brian Shiner, a psychiatrist and acting associate chief of staff for research at the White River Junction VA Medical Center, as well as associate professor of psychiatry at Dartmouth University's Geisel School of Medicine. "The idea to look at VA data in this way grew out of a conversation in the scientific literature between the VA PTSD Psychopharmacology Working Group and the National Institutes of Mental Health. Paula Schnurr from the National Center for PTSD connected Jaimie and I, and we were really fortunate to obtain funding to bring a team together to do this work."

Using patient care data from VA medical records, Gradus, Shiner, and colleagues from the VA, BUSPH, Geisel, and Harvard Medical School studied 254 VA patients who were diagnosed with PTSD and hepatitis C between October 1999 and September 2019. The participants received one combination of FDA-approved hepatitis C medications, including glecaprevir and pibrentasvir (GLE/PIB); ledipasvir and sofosbuvir (LDV/SOF); or sofosbuvir and velpatasvir (SOF/VEL). The researchers monitored the patients' symptoms for both PTSD and HCV between two clinical visits over 8 to 12 weeks.

After adjusting for variables that could potentially influence results -- such as opioid prescription use, liver disease diagnoses, emergency department care for psychiatric crises -- the team found that the GLE/PIB medications were more strongly associated with PTSD symptom improvement that the LDV/SOF and SOF/VEL treatments, consistent with their previous results.

"At BUSPH, we have been working with our VA colleagues to look at PTSD symptom improvement in routine care using medical records for several years," Gradus says. "The level of improvement we see for GLE/PIB is impressive and over twice what we have seen for paroxetine and sertraline. I think we have done the best we can with medical records data, an important next step in this line of work will be a prospective placebo-controlled study in patients without hepatitis C virus infection."

"We recently received funding from the Department of Defense to study GLE/PIB as a potential treatment for PTSD in a prospective randomized placebo-controlled trial," Shiner says. He and Gradus will be involved with the project, and Vince Watts of the White River Junction VA Medical Center will serve as principal investigator. "It will be several years until we see the results, but this is a very exciting case where we used VA patient data to identify a potential treatment for PTSD, which is a very important problem for veterans' health. In this way, veterans have informed PTSD treatment development."

https://www.sciencedaily.com/releases/2022/08/220822145130.htm

Presence of certain bacteria in the saliva might indicate post-trauma in veteran soldiers

August 14, 2022

Science Daily/Tel-Aviv University

A scientific breakthrough from the Tel Aviv and Haifa Universities may facilitate speedy, objective and accurate diagnosis of people suffering from PTSD using saliva samples. As part of the study, the researchers characterized the psychological, social and medical conditions of about 200 participants, while at the same time collecting saliva samples from them.

The findings of this study show a typical microbial picture in the saliva of veteran soldiers who had experienced combat stress-related reactions (from the first Lebanon War) and are currently suffering from post-trauma.

According to the researchers, these results may help in the future to reach an accurate and objective diagnosis of people suffering from post-trauma, and to develop microbiotic-related medications (associated with the body's microbial ecology).

This study was published in Nature's Molecular Psychiatry journal.

The study was a joint effort by eminent scholars from various fields. It was led by Professor Illana Gozes and included Professor Noam Shomron, Dr. Shlomo Sragovich and Ph.D. student Guy Shapira, (all from TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience) as well as Prof. Zahava Solomon from TAU's Gershon Gordon Faculty of Social Sciences, and Prof. Abraham Sagi-Schwartz and PhD student Ella Levert-Levitt from the Center for the Study of Child Development and the School of Psychological Sciences at Haifa University. The participants in the study came from a larger cohort of subjects from a comprehensive four-decade-long study of veterans by Prof. Solomon.

This study was also supported by IDF's Medical Corps Department of Health and Well-Being and Dr. Ariel Ben Yehuda, former chief of the above Department and currently, a Department Manager in the Mental Health Medical Center in Shalvata, Clallit Health Services. The study also involved collaboration with the Charité University Medicine in Berlin and its microbiology experts Dr. Markus M. Heimesaat and Professor Stefan Bereswill, as well as with the University of Hong Kong, which is studying the effects of air pollution, Professors Victor Li and Jacqueline Lam.

The researchers tested a unique group of about 200 Israeli veteran soldiers who had fought in the first Lebanon War in 1982. The test covered various psychological aspects, including sleep, appetite disorders, guilt, suicidal thoughts, social and spousal support, hostility, satisfaction with life, as well as issues of demographics, psychopathology, welfare, health and education.

Comparing the results of the subjects' microbial distribution to the psychological results and their responses to the welfare questionnaires, the researchers from the universities of Tel Aviv and Haifa found that people with PTSD and high psychopathological indications exhibit the same picture of bacteria in the saliva (a unique oral microbiotic signature). According to the researchers, this study is significant in that for the first time, we might be able to diagnose post-trauma by objective criteria and not just behavioral ones. It is interesting to note here that the saliva bacteria of those exposed to air pollution showed a correlation to the picture with PTSD, while the number of years of education showed a protective influence and a reverse picture of the microbial ecology in the saliva.

Prof. Illana Gozes: "To the best of our knowledge, this is the first depiction of a microbial signature in the saliva among veteran soldiers with PTSD. We were surprised to discover that about a third of the PTSD subjects had never been diagnosed with post-trauma, so they never received any recognition from the Ministry of Defense and the official authorities.

It must be stressed that until now, post-trauma diagnosis has been based solely on psychological and psychiatric measures. Thanks to this study, it may be possible, in the future, to use objective molecular and biological characteristics to distinguish PSTD sufferers, taking into account environmental influences. We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic veteran soldiers so they can receive appropriate treatment."

https://www.sciencedaily.com/releases/2022/08/220810123612.htm

How service dogs reduce PTSD symptoms: factors and mechanisms

Study explores characteristics of successful relationships between service dogs and veterans

July 27, 2022

Science Daily/PLOS

A new analysis dives into the use of service dogs by U.S. veterans who have posttraumatic stress disorder (PTSD), illuminating factors and mechanisms that may underlie the mental health effects of these relationships. Clare Jensen of Purdue University, Indiana, U.S.A., and colleagues present these findings in the open-access journal PLOS ONE on July 27, 2022.

Previous research suggests that pairing a veteran with a service dog is associated with lower severity of PTSD. However, the mechanisms underlying these potential benefits are unclear.

To improve understanding, Jensen and colleagues studied 82 military members or veterans and their service dogs, which had all been trained to alleviate PTSD symptoms. Shortly before the veterans and dogs were paired, and again after a three-month period together, the veterans completed a number of different surveys and allowed the researchers to make additional observations to capture a detailed view of veteran-dog interactions.

The researchers first analyzed results of surveys and records related to personal characteristics of the service dogs and veterans, and the closeness of their bond. They found that most of the dog characteristics evaluated were not associated with better or worse veteran mental health outcomes, except for lower dog excitability, which was linked to lower severity of PTSD symptoms and to a closer veteran-dog relationship.

Next, the researchers probed potential mechanisms underlying alleviation of mental health symptoms by analyzing the results of surveys and observations that captured dog behavior, training methods, and the use of specific trained tasks.

Better mental health was associated with a number of factors, including perception of the dog's care as being easy and a closer veteran-dog relationship. The analysis also found a link between worse depression and more frequently asking service dogs to initiate the social greeting. Veterans who more frequently asked their dogs to alert them to a human approaching from behind were more likely to have greater anxiety but less severity of PTSD symptoms.

Further research will be needed to expand on these findings, potentially leading to better understanding of how to identify veterans who could benefit from service dogs and how to best select and train dogs.

Clare Jensen adds: "This study provides new information about how and why service dogs may improve mental health for some veterans with PTSD. We are especially grateful to the military veterans who made this possible by sharing their time and experiences with us."

https://www.sciencedaily.com/releases/2022/07/220727141337.htm