TAG: "PTSD"

Tackling traumatic brain injury


Unprecedented partnership joins universities, FDA, firms, philanthropies.

UCSF neurosurgeon Geoffrey Manley (center) spoke at a White House conference Sept. 30 on the role of technology in future treatments for brain injury and post-traumatic stress disorder. Manley is flanked by Paul Alivisatos (left), director of the Lawrence Berkeley National Laboratory; and Kerry Ressler, a Howard Hughes Medical Institute Investigator from Emory University.

An unprecedented, public-private partnership funded by the Department of Defense (DoD) is being launched to drive the development of better-run clinical trials and may lead to the first successful treatments for traumatic brain injury, a condition affecting not only athletes and soldiers, but also millions among the general public, ranging from youngsters to elders.

Under the partnership, officially launched today (Oct. 1) with a $17 million, five-year award from the DoD, the research team, representing many universities, the Food and Drug Administration (FDA), companies and philanthropies, will examine data from thousands of patients in order to identify effective measures of brain injury and recovery, using biomarkers from blood, new imaging equipment and software, and other tools.

Each year more than 2.5 million people in the U.S. seek medical care for traumatic brain injuries that arise when blows to the body or nearby explosions cause the brain to collide with the inside of the skull. According to the U.S. Centers for Disease Control and Prevention, an estimated 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion. No treatment for acute TBI and concussion has proved to be effective.

“TBI is really a multifaceted condition, not a single event,” said UC San Francisco neurosurgeon Geoffrey T. Manley, M.D., Ph.D., principal investigator for the new award and chief of neurosurgery at San Francisco General Hospital and Trauma Center (SFGH), a UCSF partner hospital. “TBI lags 40 to 50 years behind heart disease and cancer in terms of progress and understanding of the actual disease process and its potential aftermath. More than 30 clinical trials of potential TBI treatments have failed, and not a single drug has been approved.”

The new research initiative, called the TBI Endpoints Development (TED) Award, brings together leading academic clinician-scientists with innovative industry leaders in biotechnology and imaging technology, with patient advocacy organizations, and with philanthropies. The research collaborators will be collecting a broad range of long-term data from existing studies and databases, and integrating these into a dataset that can be interrogated for TBI associations and causes in a way that has never before been possible.

TED is specifically designed to overcome the difficulty in demonstrating the effectiveness of TBI drugs and medical devices by actively involving the FDA in clinical-trial design from the outset.

Although awareness of TBI has focused on athletes and warriors, the condition is widely prevalent across all populations, due to falls and motor-vehicle and other accidents.

“We know that the problem is far more extensive than reported,” Manley said. “We have evidence that even those patients who arrive at emergency rooms with signs and symptoms that suggest they’ve sustained a brain injury often are released with no indication of a possible TBI entered into their medical records, and with no recommendation for follow-up care.”

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How sleep impacts PTSD


Fragmented REM sleep may hinder effective treatment of post-traumatic stress disorder.

The effectiveness of post-traumatic stress disorder (PTSD) treatment may hinge significantly upon sleep quality, report researchers at the UC San Diego School of Medicine and Veterans Affairs San Diego Healthcare System in a paper published today (Aug. 26) in the Journal of Neuroscience.

“I think these findings help us understand why sleep disturbances and nightmares are such important symptoms in PTSD,” said Sean P.A. Drummond, Ph.D., professor of psychiatry and director of the Behavioral Sleep Medicine Program at the VA San Diego Healthcare System. “Our study suggests the physiological mechanism whereby sleep difficulties can help maintain PTSD. It also strongly implies a mechanism by which poor sleep may impair the ability of an individual to fully benefit from exposure-based PTSD treatments, which are the gold standard of interventions.

“The implication is that we should try treating sleep before treating the daytime symptoms of PTSD and see if those who are sleeping better when they start exposure therapy derive more benefit.”

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PTSD can develop even without memory of the trauma


If traumatic early-life memories are lost, what persists of the experience?

Micrograph of a rat's amygdala

Adults can develop symptoms of post-traumatic stress disorder even if they have no explicit memory of an early childhood trauma, according to research by UCLA psychologists.

The study, which will be published Aug. 15 in the journal Biological Psychiatry, found that among the many forms of memory, only some may be critical for the development of post-traumatic stress disorder. The research suggests that explicit memory — which can be voluntarily recalled from prior experience and articulated — may not be a requirement for PTSD, but that other, more primitive forms of learning may be required.

At least six previous reports have found that some people who have experienced terrible life events that resulted in brain damage developed syndromes similar to PTSD even though they had no recollection of the events themselves.

The UCLA study was designed to answer a basic question: If traumatic early-life memories are lost, what persists of the experiences? The research team was led by Andrew Poulos, who was a UCLA postdoctoral scholar when the research was conducted. Poulos is currently on the faculty at the University at Albany.

In the laboratory, the researchers exposed rats that were 17 days old — the equivalent of just younger than two human years — to a single session of unpredictable stress (electric shocks to the feet that produced mild discomfort). At 80 days — roughly equal to young-adult age in humans — the scientists tested the animals for their memory of the event and measured their fear response.

“We found that the rodents, which failed to remember the environment in which they were traumatized, showed a persistent increase in anxiety-related behavior and increased learning of new fear situations,” Poulos said. “These heightened levels of fear and anxiety corresponded with drastic changes in the daily rhythms of the circulating hormone corticosterone.”

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Livermore Lab to develop next-generation neural devices with $5.6M grant


Technology will help doctors better understand, treat PTSD, traumatic brain injury.

Lawrence Livermore National Laboratory engineer Kedar Shah works on a neural device at the Lab's Center for Micro- and Nanotechnology.

Lawrence Livermore National Laboratory recently received $5.6 million from the Department of Defense’s Defense Advanced Research Projects Agency (DARPA) to develop an implantable neural interface with the ability to record and stimulate neurons within the brain for treating neuropsychiatric disorders.

The technology will help doctors to better understand and treat post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), chronic pain and other conditions.

Several years ago, researchers at Lawrence Livermore in conjunction with Second Sight Medical Products developed the world’s first neural interface (an artificial retina) that was successfully implanted into blind patients to help partially restore their vision. The new neural device is based on similar technology used to create the artificial retina.

“DARPA is an organization that advances technology by leaps and bounds,” said LLNL’s project leader Satinderpall Pannu, director of the Lab’s Center for Micro- and Nanotechnology and Center for Bioengineering, a facility dedicated to fabricating biocompatible neural interfaces. “This DARPA program will allow us to develop a revolutionary device to help patients suffering from neuropsychiatric disorders and other neural conditions.”

The project is part of DARPA’s SUBNETS (Systems-Based Neurotechnology for Emerging Therapies) program. The agency is launching new programs to support President Obama’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, a new research effort aimed to revolutionize our understanding of the human mind and uncover ways to treat, prevent and cure brain disorders.

LLNL and Medtronic are collaborating with UC San Francisco, UC Berkeley, Cornell University, New York University, PositScience Inc. and Cortera Neurotechnologies on the DARPA SUBNETS project. Some collaborators will be developing the electronic components of the device, while others will be validating and characterizing it.

As part of its collaboration with LLNL, Medtronic will consult on the development of new technologies and provide its investigational Activa PC+S deep brain stimulation (DBS) system, which is the first to enable the sensing and recording of brain signals while simultaneously providing targeted DBS. This system has recently been made available to leading researchers for early-stage research and could lead to a better understanding of how various devastating neurological conditions develop and progress. The knowledge gained as part of this collaboration could lead to the next generation of advanced systems for treating neural disease.

The LLNL Neural Technology group will develop an implantable neural device with hundreds of electrodes by leveraging their thin-film neural interface technology, a more than tenfold increase over current Deep Brain Stimulation (DBS) devices. The electrodes will be integrated with electronics using advanced LLNL integration and 3D packaging technologies. The goal is to seal the electronic components in miniaturized, self-contained, wireless neural hardware. The microelectrodes that are the heart of this device are embedded in a biocompatible, flexible polymer.

Surgically implanted into the brain, the neural device is designed to help researchers understand the underlying dynamics of neuropsychiatric disorders and re-train neural networks to unlearn these disorders and restore proper function. This will enable the device to be eventually removed from the patient instead of being dependent on it.

Using the Center for Micro- and Nanotechnology’s unique capabilities, Pannu and his team of engineers have achieved 25 patents and many publications during the last decade. The team’s goal with the DARPA SUBNETS program is to build a prototype neural device in four years for clinical trials at UCSF.

“We are very excited about this project,” Pannu said. “This is a great opportunity to develop therapies that have the potential to advance health care for our service members, veterans and the general public.”

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Untangling brain circuits in mental illness


UCSF-UC Berkeley team leads $26M project, part of President Obama’s Brain Initiative.

Depression. Anxiety Disorders. Addiction.

They’re some of the most common conditions affecting people’s health, and for millions with the most severe cases, conventional treatments such as psychotherapy and medication don’t work adequately – or simply don’t work at all.

What if there were a treatment that could target the specific brain circuits that caused these conditions and offer patients a long-lasting solution?

A team of scientists and physicians led by UC San Francisco, in collaboration with UC Berkeley, is launching a $26 million project, funded by the Defense Advanced Research Projects Agency (DARPA), to map the human brain circuits that go awry in neuropsychiatric disorders and employ advanced technology to correct these patterns.

It’s one of the first projects launched in support of the $100 million Brain Initiative (Brain Research through Advancing Innovative Neurotechnologies), announced by President Barack Obama last year to support research on treating, preventing and perhaps curing brain disorders such as Alzheimer’s, schizophrenia, autism, epilepsy and traumatic brain injury. Because psychiatric conditions disproportionately affect soldiers and veterans, DARPA – a major partner in the Brain Initiative – is seeking the most original approaches to treatment-resistant mental illnesses.

“Human brain recording can now reveal aspects of mental illness that have been inaccessible to scientists and doctors,” said UCSF neurosurgeon Edward F. Chang, M.D., who is leading the project. “By analyzing patterns of interaction among brain regions known to be involved in mental illness we can get a more detailed look than ever before at what might be malfunctioning, and we can then develop technology to correct it.”

The technology itself already exists to help people with their motor skills.

For years, doctors have been doing deep brain stimulation to correct circuitry in movement disorders such as Parkinson’s disease.  And for patients who are paralyzed or are missing limbs, scientists at the Center for Neural Engineering and Prostheses (CNEP) – where Chang is co-director – have been working in the field of brain-machine interfaces to develop a tiny implantable device for the brain that can convert their thoughts into control commands for a robotic arm or exoskeleton.

This new project plans to leverage brain-machine interfaces to do the same for psychiatric patients – but instead of driving a robotic arm or exoskeleton, the device would be able to detect abnormal brain activity and deliver electrical stimulation within the brain to alleviate the symptoms.

And because of its natural plasticity, the brain eventually could “unlearn” these abnormal signaling patterns and the patient could potentially be cured.

The ambitious project will involve more than a dozen scientists, engineers and physicians at UC Berkeley, Lawrence Livermore National Laboratory, Cornell University and New York University, as well as industry partners Posit Science and Cortera Neurotechnologies.

Team members include Vikaas Sohal, M.D., Ph.D., assistant professor of psychiatry at UCSF; UCSF neurosurgeon Philip A. Starr, M.D., Ph.D.; José M. Carmena, Ph.D., CNEP co-director and UC Berkeley associate professor of electrical engineering and computer sciences and of neuroscience; and UC Berkeley colleagues Jonathan Wallis, Ph.D.,  and Robert Knight, M.D., professors of psychology and of neuroscience; Jan Rabaey, Ph.D., Elad Alon, Ph.D., and Michel Maharbiz, Ph.D., professor and associate professors, respectively, of electrical engineering and computer sciences; and Friedrich (Fritz) Sommer, Ph.D., adjunct associate professor at the Redwood Center for Theoretical Neuroscience.

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UCSF launches online registry to drive brain disease research


Brain Health Registry brings promise of speeding advances.

A new online project led by researchers at UC San Francisco promises to dramatically cut the time and cost of conducting clinical trials for brain diseases, while also helping scientists analyze and track the brain functions of thousands of volunteers over time.

With easy online registration, the Brain Health Registry is designed to create a ready pool of research subjects for studies on neurological diseases, such as Alzheimer’s and Parkinson’s, as well as depression, post-traumatic stress disorder and many other brain ailments. About one third of the cost of running a clinical trial comes from having to recruit patients, and many trials fail or are delayed because of it.

Michael Weiner, UC San Francisco

The Brain Health Registry is the first neuroscience project to use the Internet on such a scale to advance clinical research, according to Michael Weiner, M.D., founder and principal investigator of the initiative and a professor of radiology, biomedical engineering, medicine, psychiatry and neurology at UCSF. One of his roles is serving as principal investigator of the Alzheimer’s Disease Neuroimaging Initiative, the largest observational study of Alzheimer’s.

“This registry is an innovative 21st century approach to science with tremendous potential,” Weiner said. “The greatest obstacles to finding a cure for Alzheimer’s and other brain disorders are the cost and time involved in clinical trials. This project aims to cut both and greatly accelerate the search for cures.”

Leading funders for the project include the Rosenberg Alzheimer’s Project, the Ray and Dagmar Dolby Family Fund and Kevin and Connie Shanahan. The initial focus will be on the San Francisco Bay Area, and the goal is to recruit 100,000 people by the end of 2017. Nearly 2,000 people already signed up during the online registry’s beta phase.

Volunteers will provide a brief personal history and take online neuropsychological tests in an online game format. The games give the Brain Health Registry scientific team a snapshot of the participant’s brain function. The data collected will help scientists study brains as they age, identify markers for diseases, develop better diagnostic tools to stop disease before it develops and increase the ready pool of pre-qualified clinical trial participants.

A select number of volunteers will be asked by researchers to do more, such as providing saliva or blood samples, or participating in clinical trials to test potential cures. Volunteers can participate as little or as much as they like. All information will be gathered in accordance with federal privacy laws under the Health Insurance Portability and Accountability Act (HIPAA), as well as the highest standards of medical ethics.

“For those of us who know people suffering from Parkinson’s, Alzheimer’s, PTSD and other brain disorders, this is a way we can be involved in the search for a cure,” said Douglas Rosenberg, of the Rosenberg Alzheimer’s Project, which is helping to fund the project. “We’ve worked to make the process very easy and very fulfilling for our volunteers.”

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Brain trauma raises risk of later PTSD in active-duty Marines


Deployment-related injuries are biggest predictor, but not the only factor.

Dewleen Baker

Dewleen Baker

In a novel study of U.S. Marines investigating the association between traumatic brain injury (TBI) and the risk of post-traumatic stress disorder (PTSD) over time, a team of scientists led by researchers from the Veterans Affairs San Diego Healthcare System and UC San Diego School of Medicine report that TBIs suffered during active-duty deployment to Iraq and Afghanistan were the greatest predictor for subsequent PTSD, but found pre-deployment PTSD symptoms and high combat intensity were also significant factors.

The findings are published in the Dec. 11 online issue of JAMA Psychiatry.

The team, headed by principal investigator Dewleen G. Baker, M.D., research director at the VA Center of Excellence for Stress and Mental Health, professor in the Department of Psychiatry at UC San Diego and a practicing psychiatrist in the VA San Diego Healthcare System, analyzed 1,648 active-duty Marines and Navy servicemen from four infantry battalions of the First Marine Division based at Camp Pendleton in north San Diego County. The servicemen were evaluated approximately one month before a scheduled 7-month deployment to Iraq or Afghanistan, one week after deployment had concluded, and again three and six months later.

PTSD is a psychiatric condition in which stress reactions become abnormal, chronic and may worsen over time. The condition is linked to depression, suicidal tendencies, substance abuse, memory and cognition dysfunction and other health problems.

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Interactive software helps veterans suffering from PTSD


Researchers at “Brain at War” symposium highlight digital tools in mental health care.

Attendees of the sixth annual "Brain at War" symposium on June 20 watch a presentation.

Attendees of the sixth annual "Brain at War" symposium on June 20 watch a presentation.

Digital tools can be an easily accessible and effective way of treating veterans who suffer from brain injuries and post-traumatic stress.

For brains rattled by war, UC San Francisco scientists are advancing research and clinical care with new software, apps and online tools to help “retrain the brain” for resilience and recovery.

UCSF researchers affiliated with the San Francisco Veterans Affairs Medical Center (SFVAMC) discussed these new tools at the 2013 “Brain at War” symposium, convened June 20 in downtown San Francisco.  The symposium – hosted by the Veteran’s Health Research Institute (NCIRE), a leading nonprofit research institute devoted to advancing veterans-health research – was the sixth annual meeting of the national conference, which focuses on the neurological and psychological wounds of war.

UCSF researchers for years have been leaders in identifying and exploring the mechanisms of brain trauma and posttraumatic stress, and are at the leading edge in exploring new treatment strategies for these chronic afflictions.

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Sleep mechanism ID’d that plays role in emotional memory


UC researchers also find that Ambien heightens recollection of, response to bad memories.

Sara Mednick, UC Riverside

Sleep researchers from University of California campuses in Riverside and San Diego have identified the sleep mechanism that enables the brain to consolidate emotional memory and found that a popular prescription sleep aid heightens the recollection of and response to negative memories.

Their findings have implications for individuals suffering from insomnia related to posttraumatic stress disorder (PTSD) and other anxiety disorders who are prescribed zolpidem (Ambien) to help them sleep.

The study — “Pharmacologically Increasing Sleep Spindles Enhances Recognition for Negative and High-arousal Memories” — appears in the Journal of Cognitive Neuroscience. It was funded by a National Institutes of Health career award to Sara C. Mednick, assistant professor of psychology at UC Riverside, of $651,999 over five years.

Mednick and UC San Diego psychologists Erik J. Kaestner and John T. Wixted determined that a sleep feature known as sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — are important for emotional memory.

Research Mednick published earlier this year demonstrated the critical role that sleep spindles play in consolidating information from short-term to long-term memory in the hippocampus, located in the cerebral cortex of the brain. Zolpidem enhanced the process, a discovery that could lead to new sleep therapies to improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia. It was the first study to show that sleep can be manipulated with pharmacology to improve memory.

“We know that sleep spindles are involved in declarative memory — explicit information we recall about the world, such as places, people and events, ” she explained.

But until now, researchers had not considered sleep spindles as playing a role in emotional memory , focusing instead on rapid eye movement (REM) sleep.

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PTSD in women & the role of fear conditioning


Women more likely than men to develop stronger fear response, study finds.

Women exposed to trauma may be at greater risk of developing post-traumatic stress disorder because of a heightened fear response, according to a new study.

UCSF researchers from the San Francisco Veterans Affairs Medical Center (SFVAMC) and SFVAMC-based Northern California Institute for Research and Education (NCIRE) examined individuals with PTSD symptoms and found that the women in the study were more likely than the men to develop a stronger fear response, and – once conditioned to respond fearfully – more likely to have stronger responses to fear-inducing stimuli.

“Differences in the learning of fear may be one mechanism that may be important in the development of PTSD,” said Sabra Inslicht, Ph.D., a UCSF assistant professor of psychiatry at the SFVAMC, and the lead author of a study published in the Oct. 26 online edition of the Journal of Psychiatric Research.

UCSF, which has been affiliated with the SFVAMC since the 1960s, is a leader in the scientific study and treatment of PTSD and traumatic brain injuries. Each year, UCSF and SFVAMC researchers are key participants in “The Brain at War” symposium, the leading national conference bringing together scientists, physicians, military personnel and administrative leaders to discuss the neurocognitive consequences of combat.

Inslicht, who first presented some of the new findings at the 2012 symposium, studies how men and women learn and unlearn the fear response. Scientists call these processes “fear conditioning” and “fear extinction.”

“The preliminary findings of our experiment suggest that women with PTSD had greater fear-conditioning responses than did men with PTSD,” she said. “This suggests that there may be differences in how men and women learn to fear. That may be one reason that the rates of PTSD are higher in women compared to men,” she said.

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Healing the hidden wounds of war


UCLA helps promote psychological health, physical recovery for injured vets, families.

For the 72 wounded warriors served by UCLA Operation Mend, the scars of combat in Afghanistan and Iraq are painfully obvious. Disfigured faces, missing limbs and other devastating injuries bring them to the Reagan UCLA Medical Center for reconstructive surgery and specialized treatment under the program created in 2007 by UCLA Health Sciences and the U.S. military.

Not so obvious is the toll these vets’ injuries take on the families who have stood by them through years of multiple surgeries and, in some cases, complications of Post-Traumatic Stress Syndrome (PTSD) and other psychological reverberations of war. Very often, little attention has been paid to their caregivers — their spouses or parents, most often — or their children.

“The majority of these families have not had someone talk to them about what it’s like,” said psychologist Jo Sornborger of the Semel Institute for Neuroscience and Human Behavior. “No one has asked them about how these injuries have impacted family life or how they talk with their children about having a parent injured in combat.”

Patricia Lester, UCLA

But a UCLA Health System partnership is changing this under the leadership of Dr. Patricia Lester, a UCLA psychiatrist and director of Families OverComing Under Stress (FOCUS), a Semel Institute program which supports thousands of military and veteran families nationwide.

Over the past year, FOCUS has been teaming up with Operation Mend to promote psychological health and physical recovery for patients and their family members through Operation Mend-FOCUS. The new program provides a set of “resiliency tools” to help family members understand themselves and communicate better, solve problems and feel closer to one another.

“This program is about reducing stress and promoting resilience in patients and their families,” said Lester. “This process enables them to identify their strengths and challenges and helps them think and communicate more effectively about the difficulties they may be having” in adjusting to a catastrophic injury.

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UCLA receives grant to develop saliva test to predict onset of PTSD


School of Dentistry professor leads study.

Vivek Shetty, UCLA

Each year, more than a million Americans are at-risk of developing serious mental health problems after experiencing a terrifying event or serious physical injury. Once manifested, these psychiatric illnesses, such as post-traumatic stress disorder and depression, can be extremely crippling and difficult to treat and are a leading cause of disability in civilian, military and minority populations.

Recognizing these emerging disorders early on provides health care professionals the best opportunity for preventive interventions.

Now, a team of researchers, led by Dr. Vivek Shetty, a professor at the UCLA School of Dentistry, has received a $3.8 million research grant to develop a salivary-biomarker approach for identifying individuals at future risk of developing post-traumatic stress disorder and depression following a traumatic event.

Co-funded by the National Institute of Dental and Craniofacial Research and the National Institutes of Health’s Office of Behavioral and Social Sciences Research, the study seeks to develop a panel of salivary stress biomarkers that will allow early recognition of emerging mental health disorders and permit preemptive psychological care.

“Current assessment strategies rely on subjective reports of symptoms by trauma survivors,” Shetty said. “The symptom-based nature of psychological assessments presents significant challenges for trauma care specialists attempting to differentiate between temporary distress and the early stages of mental health illnesses.

“Moreover,” he added, “the time and resource constraints of the acute care setting do not allow for the structured screening required for psychological assessments. If successful, our salivary stress biomarker panel will allow the development of practical decision-aid tools to complement subjective clinical evaluation and allow timely referrals of ‘at-risk’ individuals.”

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