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Behavioral Science

Addiction, Behavioral Science, In the News, Mental Health, Research, Stanford News

Veterans helping veterans: The buddy system

Veterans helping veterans: The buddy system

image.img.320.highI interviewed Army specialist Jayson Early by phone over the summer, shortly after he completed an in-patient program for PTSD at the Veterans Affairs hospital in Menlo Park. This was for a Stanford Medicine magazine story I was researching about a pilot project to help get much needed mental-health services to the recently returned waves of Afghanistan and Iraqi vets. What struck me most after talking with Early was just how clueless he had been, first as a teenaged-recruit, then as a young veteran, about the fact that going to war could cause mental wounds.

As the mother of a 17-year-old boy, though, I completely understood: Early just wanted to serve his country. He requested to be sent to war. In 2008, he got his wish and was deployed to Iraq just a year after exchanging his high-school baseball uniform for military fatigues. His first field assignment, an innocuous-sounding public affairs errand to photograph a burned out truck at an Iraqi police station, would be the first of many that left him with permanent scars:

“There were body parts, coagulated blood, hair all over,” [Early] says, pausing. “I just wasn’t expecting it.” An Iraqi family had been executed in the vehicle, presumably by insurgents. Early had gone through intense military training to prepare for moments like these. He blocked any emotions. He followed orders, clicked the camera and moved on. It wasn’t until years later that he realized just how permanently those images, and many more like them, had burned into his brain.

Stanford psychiatrist Shaili Jain, MD, interviewed in a podcast about her work with PTSD and veterans, had told me about a new pilot project that connects veterans with other veterans as a unique way to bridge what she called a “treatment gap” – the difficulty of getting mental-health services to the veterans that need them. My article – which is a timely read, given that today is Veterans Day – tells the story of Early’s connection with one of the veteran’s hired through this project, Erik Ontiveros, who went through treatment for addictions and PTSD himself, and just why it’s so hard to get treatment to veterans. As one well-known expert on PTSD explains in the story:

“It’s wicked difficult to treat anyone with moral injuries from combat in the traditional medical model,” says psychiatrist Jonathan Shay, MD, an expert on PTSD known for his books on the difficulties soldiers face returning home from war. “It destroys the capacity for trust. What it leaves is despair, an expectation of harm, humiliation or exploitation, and that is a horrible state of being. The traditional medical model – in an office with the door closed – is the last thing they want. I’m convinced that’s where peers come in. Peers are indispensable.”

Early told me many of his horror stories from war – stories that he rarely talks about. The time he was called to another execution area where there were enough body parts for 12 people who had all been gagged, bound, shot and burned. But, he said, they could only put together eight people. “We were trying to find a way to identify them,” he said. “Whenever I grabbed a hand, it would just crumble to dust.”

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Autism, Behavioral Science, Parenting, Pediatrics, Research, Stanford News

Study validates oxytocin levels in blood and suggests oxytocin may be a biomarker of anxiety

Study validates oxytocin levels in blood and suggests oxytocin may be a biomarker of anxiety

Karen Parker Oxytocin, sometimes dubbed “the love hormone,” can be tricky to study in humans. To conduct research on the connection between oxytocin and emotion, scientists want to assess the hormone’s levels in the brain. But sampling cerebrospinal fluid, the liquid bathing the brain, requires an invasive technique called a lumbar puncture. Measuring blood oxytocin is much easier, but some researchers have questioned whether blood oxytocin levels truly reflect what’s happening in the brain.

A new Stanford study simplifies the problem: It is the first research in children, and some of the first in any age group of humans, to indicate that blood and CSF oxytocin levels track together. The research also found a correlation between low-oxytocin and high-anxiety levels in children, adding to findings from animal studies and adult humans that have documented this oxytocin-anxiety link. The paper appears today in Molecular Psychiatry.

The findings raise the possibility that oxytocin could be considered as a therapeutic target across a variety of psychiatric disorders

The researchers recruited 27 volunteers from among a group of patients who needed lumbar puncture for medical reasons. The volunteers agreed to have oxytocin levels measured in their blood and CSF, and the parents of 10 children in the study answered questions about their children’s anxiety levels. From our press releaseabout the research:

“So many psychiatric disorders involve disruptions to social functioning,” said the study’s senior author, Karen Parker, PhD, assistant professor of psychiatry and behavioral sciences. “This study helps scientifically validate the use of measuring oxytocin in the blood, and suggests that oxytocin may be a biomarker of anxiety. It raises the possibility that oxytocin could be considered as a therapeutic target across a variety of psychiatric disorders.”

Parker’s team is now conducting studies of possible therapeutic uses of oxytocin in children with autism. They recently published a paper demonstrating that autism is not a disease of oxytocin deficiency per se; instead, oxytocin levels in kids with autism fall across a broad range. The findings hint at a future in which patients’ oxytocin levels could be used to guide treatment for autism or other psychiatric or developmental disorders. As Dean Carson, PhD, the lead author of the new study, explained:

“Our belief is that there are oxytocin responders and nonresponders,” Carson said, adding that the team is now testing this hypothesis.

…“Being able to have objective measures of psychiatric illness really will enhance early diagnosis and measures of treatment outcomes,” Carson said.

Previously: Stanford research clarifies biology of oxytocin in autism, “Love hormone” may mediate wider range of relationships than previously thought and Study shows oxytocin may boost happiness among women
Photo of Karen Parker by Norbert von der Groeben

Autoimmune Disease, Behavioral Science, Immunology, Pediatrics, Research

What happens when the immune system attacks the brain? Stanford doctors investigate

What happens when the immune system attacks the brain? Stanford doctors investigate

SM PANS image - smallerThe first time he flew into a psychotic rage, Paul Michael Nelson was only 7 years old. He stabbed at a door in his family’s home with a knife, tore at blankets with his teeth, spoke in gibberish. His very worried parents, Paul and Mary Nelson, rushed him to their local emergency room, where the medical staff thought that perhaps the little boy had simply had a bad temper tantrum.

But his rages got worse. Over the weeks and months that followed the first March 2009 emergency room visit, as Paul Michael cycled in and out of psychiatric hospitals, his parents and doctors struggled to understand what was wrong. Finally, they came to a surprising conclusion: Paul Michael had an autoimmune disease. His immune system appeared to be attacking his brain.

As strange as the case seems, the Nelsons are far from alone. As I describe in a recent story for Stanford Medicine magazine, Paul Michael was the first of more than 70 children who have been evaluated at a new clinic at Lucile Packard Children’s Hospital Stanford for pediatric acute-onset neuropsychiatric syndrome, a disease (or, more likely, a group of diseases) that doctors are still working to define. The suddenness and severity of the syndrome are frightening. Healthy children abruptly begin to show psychiatric symptoms that can include severe obsessive-compulsive behavior; anorexia; intense separation anxiety at the thought of being away from a parent; deterioration in their school work, and many other problems. From my story:

“In some ways, it’s like having your kid suddenly become an Alzheimer’s patient, or like having your child revert back to being a toddler,” says Jennifer Frankovich, MD, clinical assistant professor of pediatric rheumatology at the School of Medicine and one of the clinic’s founders.

“We can’t say how many kids with psychiatric symptoms have an underlying immune or inflammatory component to their disorder, but given the burgeoning research indicating that inflammation drives mood disorders and other psychiatric problems, it’s likely to be a large subset of children and even adults diagnosed with psychiatric illnesses,” says Kiki Chang, MD, professor of psychiatry and behavioral sciences.

To shed light on the disease, Frankovich and Chang are working with scientists from around the world on defining the parameters of the illness and launching urgently-needed research. In a special issue of the Journal of Child and Adolescent Psychopharmacology that published online this month, the researchers lay out several aspects of the problem. The Stanford experts are co-authors of a scientific article describing how doctors should evaluate children with the disease, known by its acronym, PANS. Other researchers have written about disordered eating in PANS and given a detailed description of the disease phenotype.

Recognition and treatment of the disease are still an uphill battle, but the growth of research efforts is a hopeful step. As Frankovich says at the conclusion of the Stanford Medicine story, “We cannot give up on this. There are so many of these cases out there.”

Previously: Stanford Medicine magazine traverses the immune system and My descent into madness – a conversation with author Susannah Cahalan
Illustration by Jeffrey Decoster

Behavioral Science, Cardiovascular Medicine, Medicine and Society, Research, Stanford News

The lonely are more likely to die. But why?

The lonely are more likely to die. But why?

11317715623_e27537b3f3_zLoneliness isn’t healthy — most everyone knows that. But why exactly does isolation lead to disease, or even death? Stanford researcher Sylvia Kreibig, PhD, set out to answer that question by digging through data from the Heart and Soul Study, an inquiry that followed more than 1,000 coronary heart disease patients for about 10 years, starting in 2000.

Turns out that socially isolated patients are 61 percent more likely to die in any given year than other patients, Kreibig and her team found. Yet you don’t need many friends to stave off the ill effects of solitude. Those with at least one to three regular contacts fared no better than the most-social butterfly. Even tossing in factors that affect mortality such as age and weight didn’t affect general conclusion: friendless folks die sooner. But why?

Kreibig’s team, which included Stanford psychologist James Gross, PhD, delved deeper to figure it out.

It isn’t depression. Depression is independently related to mortality, but it couldn’t explain the link between solitude and risk of death. Instead, Kreibig and colleagues found a strong link between several behavior factors such as smoking, omega-3 concentration (a representative of diet quality), and medication adherence and isolation.

“If you are more integrated, you have people around that look after you and care for you, making sure you’re eating healthy foods, not smoking and taking medications as directed,” Kreibig told me. “You yourself as a patient actually have a lot of control over factors that affect your health… Just by integrating some salmon into your diet, you have a better chance of survival.”

The team classified 1,019 patients into four categories of social integration (low, medium, medium-high and high), based on whether or not they had a partner, strength of linkages with family and friends and membership in religious congregations and community groups. Patients in the low category were more likely to smoke, eat unhealthy foods and skip their medications, the study found.

She cautioned that the study, which appears in this month’s issue of Psychosomatic Medicine, demonstrated correlation, not causation. In addition, the patients were primary male and, as they suffered from heart disease, could be affected differently than healthy, or younger, patients.

Next, Kreibig said she plans to examine the emotions related to social isolation and their effect on health.

Previously: The importance of human connection as part of the patient experience, How social media and online communities can improve clinical care for elderly patients and How loneliness can impact the immune system
Photo by Alex Krasavtsev 

Behavioral Science, Mental Health, Public Health, Stanford News

“Every life is touched by suicide:” Stanford psychiatrist on the importance of prevention

in-a-lonely-place-fa873a88-0c57-4b11-8f84-58c09aab94acMost people shy away from talking about suicide. Me too – I have some personal ties to the topic that still stab every time the s-word comes up. Yet after the initial reluctance wears off, that pain from grief and anger and fear turns into a motivational jab. Let’s talk about suicide nonstop. Let’s talk to make it stop.

Laura Roberts, MD, who leads Stanford’s psychiatry department, had the opportunity as editor-in-chief of the journal Academic Psychiatry to focus attention on suicide prevention. And she took it – partnering with the Wisconsin-based Charles E. Kubly Foundation to produce a special package of articles to inform clinicians about the latest efforts to prevent suicide.

Roberts and I spoke recently about the special issue and about suicide prevention:

Why did you want to publish this issue?

Suicide is such an under-recognized phenomenon, and it is an urgent threat to public health. Mental illness affects one in five people. Each year, more than 36,000 people commit suicide in the U.S. That is one person every fifteen minutes. In rough numbers, that’s twice the number of people who die from a violent injury in this country. Really, every life is touched by suicide.

Despite their serious public-health impact and life-threatening nature, illnesses and conditions associated with suicide have received little attention in society. These conditions are poorly understood and so greatly stigmatized. Learning to understand and evaluate people at risk for self-harm is an important element of medical student and resident education — we really wanted to emphasize these topics in this special collection.

New evidence-based models for prevention of suicide are emerging and inspire optimism. Integrating these new models is an exciting challenge for medical educators. Papers in this collection also document the impact of suicide and suicidal behavior among medical students and graduate students. About 350 physicians commit suicide each year in the U.S., and recently two interns in New York City ended their lives shortly after entering residency training. This is devastating.

In our special issue, a systematic review highlights the observation that psychiatry residents commonly experience the death of a patient by suicide, and three articles address coping with suicide professionally. Several articles focus on the development of educational programs that help strengthen suicide prevention, including screening skills and suicide awareness and management. Two articles address the resources and experience of from the Department of Veterans Affairs.

The journal special issue underscores there is much we can do in medical education to foster understanding and strengthen our responses to the phenomenon of suicide. Taken together, the papers also show how important it is that academic leaders better educate other about the prevention and impact of suicide.

What have we learned about preventing suicide?

We have learned a great deal about the prevention of suicide. Population data have shown that certain subgroups are especially vulnerable to suicide, including, for example, older white men who are ill and live alone, Native American youth as they make the transition to adulthood, and people living with serious illnesses that cause great physical and emotional pain. Understanding these larger population patterns has done a lot to help raise awareness of suicide and has allowed for creative interventions to address this problem.

Recently, researchers have been pursuing neurobiological markers that may signal when an individual is most at-risk for attempting suicide. Other studies are connecting other aspects of health — such as healthy sleep and exercise — to protective factors that may help diminish the likelihood of suicide. Such innovative work is very much needed because it will help us understand when a person with latent risk factors for suicide may act on this impulse, or, alternatively, how we can better support and intervene.

Other recent work has focused on psychological and situational factors that may contribute to suicidality among young veterans, and again, this line of inquiry may give us greater understanding on how best to reduce suicide deaths. As you may know, the number of veteran deaths due to suicide have been devastating. The VA has shown immense concern for members of the military and young veterans returning from conflicts around the world. In the course of studying suicide in this population, we have begun to have greater insight into when and whether an individual will act on an impulse to end his life. Three factors appear to be in play: first, a predisposition or vulnerability, for example, the presence of depression or anxiety that increases the general risk of suicide; second, access to a way to end one’s life, such as a gun; and, third an experience or set of experiences that make the individual feel like he is out of place, isn’t part of things, and doesn’t belong — what’s referred to as “thwarted belongingness.”

We are getting parts of the problem figured out, but so much more scientific investigation is needed. Ironically, suicide has been understudied because of concerns that the population is too vulnerable to be included in human research studies and because of the stigma associated with suicide. There have been so many barriers to these studies, and it strikes me as doubly tragic that suicide takes so many lives and yet has been relatively neglected by society and by science. In the Department of Psychiatry and Behavioral Sciences at Stanford, we are working to turn this around.

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Behavioral Science, Events, Mental Health

Learning to forgive with Fred Luskin, PhD

283888330_71b4084e22The long, wooden conference table was surrounded by 12 women, including me. We giggled a bit: Where were the men?

“All over the world, it’s almost always women,” said the first and only man to enter the room, Fred Luskin, PhD, the instructor of a four-week “Forgive for Good” class (presented by the Stanford Health Improvement Program) and founder of a movement to forgive – for your own health. He looked every bit the professor — gangly, with disheveled hair and a shirt sporting an equation.

“Even in northern Ireland?,” one woman asked.

“Even in northern Ireland,” Luskin responded.

I came to watch, to record as an observer, just as I have covered hundreds of events in the past. But in Luskin’s class, everyone must forgive. Even journalists.

It hurt to darken my laptop and separate my fingers from its well-worn keys. I bristled during the initial relaxation session, where we were directed to focus on our breathing. He’s saying things and I’m missing them! Grrrrrr. My heart raced.

“You can’t forgive if you don’t relax,” Luskin said. “You have to quiet down and open.”

I tried to pretend I was in yoga class. I took in a breath. Open. Breathe. Then, the relaxation session was over and I relaxed, once again reunited with my trusty Mac.

But then, as Luskin was mentioning that many women had taken his classes to forgive their ex-husbands – “There’s lots of terrible ex-husbands running around,” he joked – I looked around the table. Here were 11 women, driven to spend four evenings letting go of a hurt that was tearing them up inside. Instantly, my aggravation slipped away. My teensy anger was nothing compared to the real wrongs of the world.

“It’s quick and difficult to be a human being,” Luskin said. “You don’t get a do-over.”

Grieving and suffering are normal, he said. Yet make sure the harm doesn’t dampen the rest of your life. A jerk cuts you off on the freeway? Fume for a second, but one exit later it should be forgotten, Luskin said. A drunk driver leaves you crippled? That takes a bit longer, maybe five years. Dreadful childhood? No one in their 50s should still be stewing about their harsh lot.

“Life is very challenging,” Luskin said. “Do you want to spend years holding on to your part of that challenge? Or can you accept your portion of portion of pain?”

Once the grieving is done, stop talking about the hurt, Luskin said. “We used to call this shut-up therapy…  Just shut up and stop driving yourself nuts.”

Then, he said, you can love again, without hiding your heart. That’s a message worth parting from my computer.

Previously: Practicing forgiveness to sustain healthy relationships, A conversation with Stanford psychologist Fred Luskin on forgiveness and its health benefits and Teaching children the importance of forgiveness
Image by Ian Burt

Behavioral Science, Parenting, Pediatrics, Research, Stanford News

Families can help their teens recover from anorexia, new study shows

Families can help their teens recover from anorexia, new study shows

anorexia-appleUpdated 10-2-14: In a just-published 1:2:1 podcast, Lock discusses this work in depth.

***

9-24-14: A large new study comparing two treatments for anorexia nervosa offers a hopeful message to parents of teens affected by the eating disorder: Families can work with therapists to help their children recover.

The study, which appears today in JAMA Psychiatry and was led by Stanford’s Stewart Agras, MD, was the first large randomized clinical trial to compare two forms of family-based treatment for anorexia. The study included 167 anorexia patients, aged 12 to 18, at six medical centers in the United States and Canada.

In both treatments tested, a trained therapist met regularly with the patient and at least one other member of his or her family. One type of therapy focused on teaching parents how to get their child eating again at home, a method that Agras and Stanford eating disorder expert James Lock, MD, PhD, have researched extensively in the past. The other approach was broader, with the therapist and the family exploring problems in family dynamics and how to solve them. Patients and families in both treatment groups received 16 one-hour therapy sessions over a nine-month period, and patients’ recovery was assessed at the end of the therapy and again one year later.

Both therapies were equally effective in the long run, but the approach that focused on feeding was faster, and patients in that group were hospitalized fewer days during their treatment, which also made this method less expensive. The findings add to a growing list of scientific studies that are changing how physicians think about the families of patients with eating disorders, as our press release explains:

“For a long time, people blamed families for causing anorexia and thought they should be left out of treatment,” said Lock. “But this study suggests that, however you involve them, families can be useful, and that more focused family treatment works faster and more cost-effectively for most patients.” Lock directs the Comprehensive Eating Disorders Program at Lucile Packard Children’s Hospital Stanford.

The need for good treatments for anorexia in teens is bolstered by prior research demonstrating that the disease becomes more difficult to treat in adulthood, as Agras noted:

“The longer anorexia goes on, the more difficult it is to treat,” he said. “A great many people live chronically restricted lives because of this disease — they plan their days around undereating and overexercise — and quite a few die. The idea is to treat the disorder in adolescence to prevent more adults from becoming anorexic.”

Lock is the c0-author of the book Help Your Teenager Beat an Eating Disorder, which is designed to help parents conduct the feeding-based treatment examined in this study. Lock and Agras have both contributed to textbooks and manuals on eating disorder treatment for health care professionals.

Previously: Stanford study investigates how to prevent moms from passing on eating disorders, A growing consensus for revamping anorexia nervosa treatment and Possible predictors of longer-term recovery from eating disorders
Photo by Santiago Alvarez

Behavioral Science, Evolution, Imaging, Neuroscience, Research, Stanford News, Surgery

In a human brain, knowing a face and naming it are separate worries

In a human brain, knowing a face and naming it are separate worries

Alfred E. Neuman (small)Viewed from the outside, the brain’s two hemispheres look like mirror images of one another. But they’re not. For example, two bilateral brain structures called Wernicke’s area and Broca’s area are essential to language processing in the human brain – but only the ones  in the left hemisphere (at least in the great majority of right-handers’ brains; with lefties it’s a toss-up), although both sides of the brain house those structures.

Now it looks as though that right-left division of labor in our brains applies to face perception, too.

A couple of years ago I wrote and blogged about a startling study by Stanford neuroscientists Josef Parvizi, MD, PhD, and Kalanit Grill-Spector, PhD. The researchers recorded brain activity in epileptic patients who, because their seizures were unresponsive to drug therapy, had undergone a procedure in which a small section of the skulls was removed and plastic packets containing electrodes placed at the surface of the exposed brain. This was done so that, when seizures inevitably occurred, their exact point of origination could be identified. While  patients waited for this to happen, they gave the scientists consent to perform  an experiment.

In that experiment, selective electrical stimulation of another structure in the human brain, the fusiform gyrus, instantly caused a distortion in an experimental subjects’ perception of Parvizi’s face. So much so, in fact, that the subject exclaimed, “You just turned into somebody else. Your face metamorphosed!”

Like Wernicke’s and Broca’s area, the fusiform gyrus is found on each side of the brain. In animal species with brains fairly similar to our own, such as monkeys, stimulation of either the left or right fusiform gyrus appears to induce distorted face perception.

Yet, in a new study of ten such patients, conducted by Parvizi and colleagues and published in the Journal of Neuroscience,  face distortion occurred only when the right fusiform gyrus was stimulated. Other behavioral studies and clinical reports on patients suffering brain damage have shown a relative right-brain advantage in face recognition as well as a predominance of right-side brain lesions in patients with prosopagnosia, or face blindness.

Apparently, the left fusiform gyrus’s job description has changed in the course of our species’ evolution. Humans’ acquisition of language over evolutionary time, the Stanford investigators note, required the redirection of some brain regions’ roles toward speech processing. It seems one piece of that co-opted real estate was the left fusiform gyrus. The scientists suggest (and other studies hint) that along with the lateralization of language processing to the brain’s left hemisphere, face-recognition sites in that hemisphere may have been reassigned to new, language-related functions that nonetheless carry a face-processing connection: for example, retrieving the name of a person whose face you’re looking at, leaving the visual perception of that face to the right hemisphere.

My own right fusiform gyrus has been doing a bang-up job all my life and continues to do so. I wish I could say the same for my left side.

Previously: Metamorphosis: At the push of a button, a familiar face becomes a strange one, Mind-reading in real life: Study shows it can be done (but they’ll have to catch you first), We’ve got your number: Exact spot in brain where numeral recognition takes place revealed and Why memory and  math don’t mix: They require opposing states of the same brain circuitry
Photo by AlienGraffiti

Behavioral Science, Pain, Podcasts

Chronic pain: Getting your head around it

Chronic pain: Getting your head around it

Less Pain cover - smallerI have to admit: When it comes to pain, I’m a total wimp. The few times I’ve approached anything near chronic pain was in my neck – the result from unilateral breathing as a lap swimmer. When I had the pain, I was obsessed with it, and it was a complete drag on my psyche. My painful experience gave me deep empathy for anyone who lives with chronic pain.

Beth Darnall, PhD, is a clinical associate professor at the medical school and a clinical psychologist at Stanford’s Pain Management Center. She has practiced this unique specialty – pain psychology – for the past 10 years, working with chronic pain sufferers to find alternative means to controlling their pain rather than being stuck in a downward spiral of opioid use. And she’s written a new book, Less Pain, Fewer Pills, where she details a methodical approach that enables one to get their “head” out from their pain.

Clearly it’s not all attitude, but a significant portion of pain is how we think about it and catastrophize it and therefore unknowingly give it strength. She told me in this 1:2:1 podcast that “early life trauma can lead to changes in the central nervous system and immune systems… that could prime someone to experience chronic pain later on.” She also said:

We have just pure genetics, an underlying predisposition to acquire chronic pain… But we also know that a person’s psychological makeup, what the person brings to the table, is a big predictor in terms of whether or not their pain resolves or whether it becomes entrenched.

I asked Darnall whether her role as a clinical psychologist helps patients rethink their pain. She told me, “A key message that I bring forward to the table is that pain isn’t something that just happens to us. Once we acquire chronic pain we are constantly participating with our pain in terms of our thoughts, our beliefs, our emotions, and our choices. If we can focus on that and optimize our control there, then we can set ourselves up to have the best response to all of the treatments that our doctors are going to be trying for us.”

If you suffer from chronic pain or know someone who does, I hope you’ll find this conversation with Darnall of value.

Previously: Stanford researchers address the complexities of chronic pain, Exploring the mystery of pain, Relieving Pain in America: A new report from the Institute of Medicine, Stanford’s Sean Mackey discusses recent advances in pain research and treatment and Oh what a pain

Behavioral Science, Chronic Disease, Mental Health, Neuroscience, Research, Stanford News

Can Alzheimer’s damage to the brain be repaired?

Can Alzheimer's damage to the brain be repaired?

repair jobIn my recent Stanford Medicine article about Alzheimer’s research, called “Rethinking Alzheimer’s,” I chronicled a variety of new approaches by Stanford scientists to nipping Alzheimer’s in the bud by discovering what’s gone wrong at the molecular level long before more obvious symptoms of the disorder emerge.

But Stanford neuroscientist Frank Longo, MD, PhD, a practicing clinician as well as a researcher, has another concern. In my article, I quoted him as saying:

Even if we could stop new Alzheimer’s cases in their tracks, there will always be patients walking in who already have severe symptoms. And I don’t think they should be forgotten.

A study by Longo and his colleagues, which just went into print in the Journal of Alzheimer’s Disease, addresses this concern. Longo has pioneered the development of small-molecule drugs that might be able to restore nerve cells frayed by conditions such as Alzheimer’s.

Nerve cells in distress can often be saved from going down the tubes if they get the right medicine. Fortunately, the brain (like many other organs in the body) makes a number of its own medicines, including ones called growth factors. Unfortunately, these growth factors are so huge that they won’t easily cross the blood-brain barrier. So, the medical/scientific establishment can’t simply synthesize them, stick them into an artery in a patient’s arm and let them migrate to the site of brain injury or degeneration and repair the damage. Plus, growth factors can affect damaged nerve cells in multiple ways, and not always benign ones.

The Longo group’s study showed that – in mice, at least -  a growth-factor-mimicking small-molecule drug (at the moment, alluded to merely by the unromantic alphanumeric LM11A-31) could counteract a number of key Alzheimer degenerative mechanisms, notably the loss of all-important contacts (called synapses) via which nerve cells transmit signals to one another.

Synapses are the soldier joints that wire together the brain’s nerve circuitry. In response to our experience, synapses are constantly springing forth, enlarging and strengthening, diminishing and weakening, and disappearing.They are crucial to memory, thought, learning and daydreaming, not to mention emotion and, for that matter, motion. So their massive loss — which in the case of Alzheimer’s disease is a defining feature – is devastating.

In addition to repairing nerve-cells, the compound also appeared to exert a calming effect on angry astrocytes and  microglia, two additional kinds of cells in the brain that, when angered, can produce inflammation and tissue damage in that organ. Perhaps most promising of all, LM11A-31 appeared to help the mice remember where things are and what nasty things to avoid.

Previously: Stanford’s brightest lights reveal new insights into early underpinnings of Alzheimer’s, Stanford neuroscientist discusses the coming dementia epidemic and Drug found effective in two mouse models of Huntington’s disease
Photo by Bruce Turner

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