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

A new insight into the brain chemistry of autism

A new insight into the brain chemistry of autism

TrueHugFor several years now, scientists have been testing the hypothesis that one particular hormone, oxytocin, plays a role in autism. It seems logical: After all, this molecule nicknamed the “love hormone” promotes bonding between romantic partners and is one of the main signals involved in childbirth, breastfeeding and helping new mothers form strong bonds with their babies. And social-interaction difficulties are a known characteristic of autism, a developmental disorder that affects one in every 68 kids.

But in the flurry of interest around oxytocin, a related signaling molecule has been largely overlooked. Called vasopressin, it’s structurally very similar to oxytocin. Both are small proteins made of nine amino acids each, and the amino-acid sequence is identical at seven of the nine spots in the two hormones. Vasopressin is best known for its role in regulating blood pressure, but it also has social roles, which have mostly been studied in rodents.

Noting the dearth of autism-vasopressin research, a Stanford team decided to study vasopressin levels and social behavior in children diagnosed with autism and controls who had not been diagnosed with autism. Our press release about their study, which was published today in PLOS ONE, explains:

The research team found a correlation between low levels of vasopressin, a hormone involved in social behavior, and the inability of autistic children to understand that other people’s thoughts and motivations can differ from their own. …

“Autistic children who had the lowest vasopressin levels in their blood also had the greatest social impairment,” said the study’s senior author, Karen Parker, PhD, associate professor of psychiatry and behavioral sciences.

Parker and her colleagues examined “theory of mind,” the ability to deduce that others have a mind of their own – and that they may perceive the world differently than you do. It’s an important underpinning to forming empathetic relationships with other people. In kids with autism, the lower their vasopressin levels, the worse their scores on a test of theory of mind, the study found. Children without autism did not show this link; they all had pretty good theory of mind scores, whether their vasopressin levels were low or high.

It’s worth adding that low vasopressin level did not diagnose whether a child had autism; the hormone’s levels ranged from low to high in both groups of children. So autism is not simply a state of vasopressin deficiency. However, the researchers are interested in whether giving vasopressin might help relieve autism symptoms and are now carrying out a clinical trial to test its effects.

The work also provides an interesting complement to oxytocin findings published by the same team last year. In the oxytocin study, the scientists found that children with autism could have low, medium or high oxytocin levels, just like other children. However, oxytocin levels were linked to social ability in all children, not just those with autism.

Based on the new findings, it’s possible, Parker told me, that vasopressin is uniquely important for children with autism. She’s eager to expand her work in this overlooked corner of brain-chemistry research.

Previously: Stanford research clarifies biology of oxytocin in autism, “Love hormone” may mediate wider range of relationships than previously thought and Volunteers sought for autism drug study
Artwork by Dimka

Health Disparities, Mental Health, Pediatrics, Public Health

Stanford study of mental illness in incarcerated teens raises policy questions

Stanford study of mental illness in incarcerated teens raises policy questions

depressionMental illness is an even bigger problem for jailed teenagers than experts previously realized.

That’s the take-away message from a Stanford study, publishing today in the Journal of Adolescent Health, which compared 15 years’ worth of hospital stays for adolescents in California’s juvenile justice system with hospitalizations of other California kids and teens. Experts already knew that juvenile inmates are more likely than other young people to have mental health problems, but the new study gives fresh perspective on the scope of the issue.

The research team, led by Arash Anoshiravani, MD, an adolescent medicine specialist at Lucile Packard Children’s Hospital Stanford, looked at 15 years of hospital-stay data for California’s 11- to 18-year-olds. From a total of almost 2 million hospitalizations, about 11,000 were for incarcerated youth.

Of these 11,000 hospital stays, 63 percent were due to mental-health diagnoses. In contrast, just under 20 percent of the hospital stays by adolescents from the general population were prompted by mental illness. Hospital stays were also longer for the incarcerated teens, suggesting more severe illness.

However, the kinds of diagnoses were pretty similar between the two groups, with depression and substance abuse the most common. From our press release about the new study:

The types of diagnoses suggest that many incarcerated teens’ mental health problems developed in response to stressful and traumatic childhood experiences, such as being abused or witnessing violence, Anoshiravani said.

“They’re regular kids who have had really, really horrible childhoods,” he said, adding that he hopes the new data will motivate social change around the problem.

“We are arresting kids who have mental health problems probably related to their experiences as children,” he said. “Is that the way we should be dealing with this, or should we be getting them into treatment earlier, before they start getting caught up in the justice system?”

Previously: Online health records could help high-risk teens, study finds, Lucile Packard Children’s Hospital partners with high schools on student mental health programs and Increasing awareness and advocacy of emotional disorders with mental health first-aid programs
Photo by ryan melaugh

Autoimmune Disease, In the News, Mental Health, Pediatrics, Research, Stanford News

Stanford doctors unraveling mysterious childhood psychiatric disease

Stanford doctors unraveling mysterious childhood psychiatric disease

BrainModel2A story in Sunday’s Wall Street Journal highlights Stanford’s leadership in treating a mystifying disease in which a child suddenly develops intense psychiatric problems, often after an infection. The disease, called pediatric acute-onset neuropsychiatric syndrome, can be terribly disabling, altering kids’ personalities, interfering with their school work and making it hard for families to function.

As the story (subscription required) explains, some physicians question whether PANS is actually a separate disease from the psychiatric diagnoses it resembles, which include obsessive-compulsive disorder and anorexia nervosa. But doctors at Lucile Packard Children’s Hospital Stanford suspect something else is truly going on, likely an autoimmune attack on the brain. The team, led by Jennifer Frankovich, MD, and Kiki Chang, MD, is working to learn more about the disease:

In an effort to establish the science of PANS, the Stanford clinic is collecting extensive data on the patients. Doctors try to piece together what is driving symptoms from pediatric records, parent reports, even teacher interviews. They are analyzing DNA samples from each patient and looking for clues in their immune systems. If they find strep, they bank the strain for further research. “It is easier to study something that is established,” Dr. Frankovich said. “To build something new is really hard.”

The team’s insights from 47 of their patients were published earlier this year in a special PANS-focused issue of the Journal of Child and Adolescent Psychopharmacology, and the researchers are currently working to expand the capacity of their PANS clinic, the first of its kind in the country. More information about PANS and its effect on children and families is also available in a Stanford Medicine magazine story I wrote last year about Frankovich and Chang’s work.

Previously: What happens when the immune system attacks the brain? Stanford doctors investigate and My descent into madness — a conversation with author Susannah Cahalan
Photo by GreenFlames09

Health Policy, Mental Health, Patient Care, Pediatrics, Stanford News

Stanford expert on new treatment guidelines for teens’ eating disorders

Stanford expert on new treatment guidelines for teens' eating disorders

eatingdisorder-plateEating disorders often begin in the teenage years, but, surprisingly, the medical community long lacked a teen-specific set of guidelines for treating these serious illnesses.

That changed in May with the publication of a set of practice parameters co-authored by Stanford eating disorder expert James Lock, MD, PhD, who also directs the Comprehensive Eating Disorders Program at Lucile Packard Children’s Hospital Stanford. The parameters were based on an extensive review of the current scientific evidence around eating-disorder treatment, including recent studies by Lock and his colleagues that show that teens’ parents can play an active role in helping their children recover from anorexia nervosa. That’s a big shift from traditional thinking about eating disorders, which held that young patients’ families should be shut out of treatment.

In a new Q&A, I talked with Lock about why the parameters were needed. He told me:

There have never been practice parameters that address eating disorders in children and adolescents, and expertise in treating these disorders has been sort of sequestered. Yet eating disorders are so prevalent and are such a severe problem: Lifetime prevalence in adolescent girls is around 1 percent, and the disorders have among the highest fatality rates of all mental illnesses.

Teens need treatment approaches that account for their level of physical and emotional development, the fact that their parents generally want and need to be involved in their recovery, and the fact that they have not usually had eating disorders for as long as adult patients with the same diagnoses.

Lock also discusses how he hopes the new guidelines will improve training of psychiatrists, how recent changes to eating disorder diagnostic criteria are making it easier for doctors to get their patients the help they need, and why outpatient treatment is the new front line for young people with eating disorders.

Previously: Patient tells how social media helped her overcome the “shame” of her eating disorder, Incorporating family into helping teens overcome eating disorders and Story highlights need to change the way we view and diagnose eating disorders in men
Photo by Darren Tunnicliff

Chronic Disease, Genetics, Health Disparities, Pediatrics, Research, Stanford News

Cystic fibrosis is deadlier for Hispanic patients, Stanford study finds

Cystic fibrosis is deadlier for Hispanic patients, Stanford study finds

Lungs-embroideryHow do physician-scientists select research projects? Sometimes, they’re prompted by the niggling feeling that something is not right.

That’s what happened to cystic fibrosis doctor MyMy Buu, MD, the lead author on a new paper that uncovers an important health disparity, a higher mortality rate for CF patients of Hispanic ethnicity. Buu, a pediatric pulmonologist who takes care of CF kids at Lucile Packard Children’s Hospital Stanford, launched the research because she noticed something worrying: It seemed to her that a lot of Hispanic children with CF were not doing well.

“…I didn’t know if this was just because we have more Hispanic patients in California, or if they were actually, really, sicker,” Buu said. CF is a genetic disease that causes serious breathing and digestive problems; Buu’s job is a mixture of trying to help her patients stay relatively healthy and dealing with complications of the disease.

“Because I’m interested in health disparities, I wanted to see if there were any differences in outcomes in the Hispanic group,” she said.

She turned to the Cystic Fibrosis Foundation‘s patient registry, focusing on 20 years of data that encompass every California child diagnosed with CF from the beginning of 1991 to the end of 2010. Of the children studied, Hispanic CF patients were almost three times as likely to die as their non-Hispanic counterparts.

Buu and her colleagues were able to use the data to eliminate several possible explanations for the disparity. Hispanic children were not being diagnosed later than non-Hispanic kids and did not have less access to health care, for instance. Our press release about the study describes the factors that may contribute to the disparity:

However, the researchers did find important clinical and social differences between the groups. At age 6, the earliest that lung function is routinely and reliably measured for patients with CF, Hispanic children with CF had worse lung function than non-Hispanic kids with the disease. The gap in lung function persisted as the children aged, although it did not widen. And although the same proportion of patients in both groups eventually developed CF complications, the complications struck Hispanic patients earlier in life. Hispanic patients lived in poorer neighborhoods and were more likely to be covered by public health insurance than their non-Hispanic counterparts.

The research also showed that, between the two groups, different mutations prevailed in the disease-causing gene, which is called the CF transmembrane conductance regulator gene. Hispanic patients tended to have rare and poorly characterized mutations in their CFTR gene, whereas non-Hispanic patients had more common mutations that have been more extensively researched.

The next steps, Buu said, are to make others aware of the increased risk for Hispanic CF patients and to figure out how the risk can be reduced.

Previously: Cystic fibrosis patient on her 20+ years of care, New Stanford-developed sweat test may aid in development of cystic fibrosis treatments and Film about twin sisters’ double lung transplants and battle against cystic fibrosis available online
Image by Hey Paul Studios

Addiction, Parenting, Pediatrics, Public Health, Research, Stanford News

Teens confused about harms of marijuana and e-cigarettes, Stanford study finds

Teens confused about harms of marijuana and e-cigarettes, Stanford study finds

smoking-skaterToday’s teenagers are familiar with the dangers of smoking conventional cigarettes, but they’re much less sure of the risks posed by marijuana and e-cigarettes, according to a Stanford study published today in the Journal of Adolescent Health.

The researchers asked 24 high-school students in one Northern California school district about the benefits and risks they perceived from cigarettes, e-cigarettes and marijuana, and where they were getting information about each. The good news is that teens have clearly absorbed the message – from parents, teachers and public health campaigns – that cigarettes are bad for their health. And the kids surveyed saw no benefit to smoking cigarettes, suggesting that conventional cigarettes have lost the “cool” factor they once had among the young.

But there was a big gap in teens’ understanding of e-cigarettes and marijuana, as our press release about the research explains:

“Kids were really good at describing the harmful things that happen with cigarette smoking, but when we asked about other products, there was a lot of confusion,” said the study’s lead author, Maria Roditis, PhD, a postdoctoral scholar in adolescent medicine.

“We’re good at delivering messaging that cigarettes are harmful, but we need to do a better job with other products that teens may smoke,” added Bonnie Halpern-Felsher, PhD, professor of pediatrics in adolescent medicine and the study’s senior author. “We don’t want the message kids get to be ‘cigarettes are bad, so everything else might be OK.’”

Teens need to hear about the risks of marijuana, including its damaging effects on the adolescent brain; its addictive potential; and its ability to damage the lungs, which is similar to that from inhaling smoke from any form of plant matter, Halpern-Felsher said. They also need to hear about the risks of e-cigarettes, which include the addictive properties of nicotine and the fact that flavor compounds in e-cigarettes can cause obstructive lung disease.

In a story about the research on LiveScience.com, Halpern-Felsher speculated on some of the factors that may be affecting teens’ views of marijuana and e-cigarettes:

There are several possible reasons why teens may view the risks of smoking cigarettes differently than using marijuana or e-cigarettes. One reason involves advertising — although the tobacco industry can’t advertise on TV, in some print media or in any youth venue, similar restrictions don’t apply to e-cigarettes, Halpern-Felsher told Live Science.

Young people are seeing e-cigarettes in cool colors and cool flavors. They are also seeing celebrities use them, and that gives these products more exposure and makes them appealing, she said.

Previously: With e-cigarettes, tobacco isn’t the only danger, How e-cigarettes are sparking a new wave of tobacco marketing and To protect teens’ health, marijuana should not be legalized, says American Academy of Pediatrics
Photo by James Alby

Global Health, Pediatrics, Public Health, Research, Sexual Health, Stanford News

Male attitudes about sexual violence challenged by educational program in Kenya

Male attitudes about sexual violence challenged by educational program in Kenya

Your-MomentIn the slums of Nairobi, Kenya, where sexual assault is rampant, an NGO called No Means No Worldwide has made important inroads in reducing rape of girls and women. As I’ve reported previously, their empowerment program for high-school girls teaches young women that they are entitled to stop unwanted sexual advances and gives them skills to do so.

But, in a culture with persistent denigration of women, girls’ lack of empowerment is only part of the problem. Fortunately, the people at No Means No Worldwide have also been asking how to improve male attitudes and behaviors toward women.

The curriculum for these young men is centered on getting them to think about what kind of people they want to be

Today, they’re reporting success in the first study of their curriculum for adolescent boys. The set of six two-hour classes for young men in impoverished Nairobi high schools focused on getting participants to challenge prevailing ideas about of women, as a Stanford expert who worked on the study explains in our press release:

“The curriculum for these young men is centered on getting them to think about what kind of people they want to be,” said lead author Jennifer Keller, PhD, clinical associate professor of psychiatry and behavioral sciences. “It’s about really getting them invested in why they need to step up and care about violence toward women: It affects their mothers, sisters and girlfriends.”

The classes helped boys recognize the cultural normalization of violence against women, and gain skills and courage to stop it. Topics of discussion included myths about women, negative gender stereotypes, when and how to safely intervene if you see someone else acting violently toward a woman, and what constitutes consent to sexual activity:

“If you think that when you take a woman out to dinner, she owes you something, you may believe that consent is different than it actually is,” Keller said. “The instructors and young men talked about understanding what true consent is and how to get that consent.”

At the end of the classes and at follow-up nine months later, the boys and young men who participated had significantly better attitudes and beliefs about women than a control group who participated in a life-skills class. Members of the intervention group also were more likely to step in to try to stop violent behavior they saw toward women. In the future, the research team plans to test whether the program also improves young men’s behavior in their own relationships with girlfriends.

Previously: Rape prevention program in Kenya attracting media attention, funding, Working to prevent sexual assaults in Kenya and Empowerment training prevents rape of Kenyan girls
Photo of participants in the “Your Moment of Truth” program by Duthie Photography, courtesy of No Means No Worldwide

Patient Care, Pediatrics, Research, Stanford News, Technology

A new tool for tracking harm in hospitalized children

A new tool for tracking harm in hospitalized children

Medical-chartsIn the 15 years since the Institute of Medicine issued its groundbreaking report showing frequent harm caused by medical care, researchers have worked to devise efficient, reliable ways to detect harm to patients. Finding out what aspects of care most often hurt patients is a key step in reducing these harms, but voluntary reports, in which caregivers are asked to document harm they cause, only identify a small percentage of total harms.

New research published today in Pediatrics describes a better approach for tracking harm to kids in hospitals. Using the system on 600 medical charts from six U.S. children’s hospitals, the researchers found that almost 25 percent of patients included in the chart review had experienced at least one harm, and that 45 percent of these harms were probably preventable. The approach, called a “trigger tool,” was based on a similar harm-tracking method designed for hospitalized adult patients. Researchers look at each medical chart for “triggers” – events or lab measurements often associated with harm – and when they find a trigger, explore the medical chart in detail around the time of the trigger to see if harm occurred.

“This tool will allow us to better understand the epidemiology of harm in hospitalized children, as well as give us the capacity to track harms over time to determine if our interventions are making an improvement,” said senior study author Paul Sharek, MD, an associate professor of pediatrics and chief clinical patient safety officer at Lucile Packard Children’s Hospital Stanford and Stanford Children’s Health. He collaborated with scientists from several other institutions on the research.

I talked with Sharek last week about the study’s findings and implications. To start, I asked him to give me an example that would help me understand the difference between preventable and non-preventable harm. A child who receives a medication that provokes an allergic reaction has experienced a non-preventable harm if it’s the first time the child ever got the drug, and there were no clues beforehand that she had the allergy, he told me. But if the drug allergy was already known and the patient got the drug anyway and had an allergic reaction, that is a preventable harm.

The high rate of preventable harms shows that there is a lot of room to make all hospitals safer for kids, Sharek said. One surprise in the data was that nine common healthcare-acquired conditions that have been targeted by national safety efforts – including central line-associated bloodstream infections, ventilator-associated pneumonia and surgical site infections – together accounted for only 4 percent of all harms identified in this study. “If we were able to eliminate every one of these, according to these data, we’d still be left with 96 percent of the harms we identified,” Sharek said.

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Ethics, In the News, Patient Care, Pediatrics

Study of outcomes for early preemies highlights complex choices for families and doctors

Study of outcomes for early preemies highlights complex choices for families and doctors

3363144800_8c4c7ee6a5_zA tiny fraction of babies born at 22 weeks of gestation survive to childhood without major impairments or disabilities, according to a study recently published in the New England Journal of Medicine. But, although some of these babies can do well, there is variation between hospitals in the rate at which they are resuscitated after birth.

As was widely reported late last week, the results add to the existing debate about providing the earliest-born preemies with intensive medical care. I talked with Henry Lee, MD, a neonatologist at Lucile Packard Children’s Hospital Stanford, to get his take on the new findings. Doctors who work with tiny preemies and their families aren’t surprised by the study’s results, Lee told me, since the generally poor outcomes for 22-week babies are consistent with other studies. But they are carefully considering what to do next.

“We already knew, to a large extent, that there is variation in how different practitioners and hospitals manage patients in this peri-viable range,” Lee said. “Some hospitals tend to be more aggressive at resuscitating and actively treating these babies, others less so.”

The study’s findings highlight that doctors may have difficulty letting parents make the choice about how to handle the birth of a very early preemie, Lee noted. “We’re supposed to be communicating with parents, and they’re supposed to be making an informed decision,” he said. The variation between hospitals suggests that’s not what is actually happening; if parents were deciding what to do, the rate of resuscitation would be more consistent across hospitals. “This data is telling us that we as medical professionals are making the decision for parents, especially at really young gestational ages,” Lee said. “It’s an area that we need to continue to learn to deal with better.” Hospitals also vary in their capacity to care for such babies, he added.

Physicians from several Bay Area hospitals have already begun meeting to discuss their approaches to the earliest-born preemies, he told me. “We might not practice exactly the same, but we want to understand the rationale for what everyone is doing,” Lee said. “If one group is doing something that makes sense, we could learn from them.”

And the study also brings into focus the difficulty of balancing statistics against an individual family’s situation, Lee added. “These larger population studies help us to counsel families, but one thing I always have to say to them is that there’s uncertainty,” he said. “I tell parents that we don’t know what is going to happen to their baby – ultimately their baby is an individual and we don’t know yet. There is that very huge uncertainty.”

Previously: Counseling parents of the earliest-born preemies: A mom and two physicians talk about the challenges, Stanford-led study suggests changes to brain scanning guidelines for preemies and Talk to her (or him): Study shows adult talk to preemies aids development
Photo by Sarah Hopkins

Cardiovascular Medicine, Pediatrics, Stanford News, Transplants

Ventricular assist device helps teen graduate from high school

Ventricular assist device helps teen graduate from high school

TJ Balliao verticalWhen 17-year-old TJ Balliao was diagnosed with heart failure earlier this year, his doctors at Lucile Packard Children’s Hospital Stanford told him that he needed to receive a ventricular assist device right away. TJ was experiencing bouts of unstable heart rhythm so serious that medication alone wasn’t enough to keep him alive. The VAD, a pump implanted in his heart to help it move blood through his body, could help him survive long enough to receive a heart transplant.

But something unexpected happened after the surgery to implant TJ’s ventricular assist device. He made a strong recovery – so strong that his cardiologist, David Rosenthal, MD, offered him the opportunity to go home with his VAD, graduate from high school with his class this June, and delay a heart transplant indefinitely.

In a recent story I wrote about TJ’s case, Rosenthal explained how this could benefit TJ not just now, but also in the long run:

“It’s possible that using a VAD to intentionally delay a heart transplant could add to the patient’s total lifespan,” said Rosenthal, who directs the hospital’s pediatric heart failure and transplantation program and is professor of pediatrics at the Stanford University School of Medicine. “Survival after transplant is not as long as the natural lifespan, especially for children.”

The benefits of a VAD are many. It helps patients maintain strength while waiting for a new heart; otherwise, heart failure weakens the body, making recovery from eventual transplant more difficult. When a child is stabilized by use of a VAD, the medical team can be more selective about choosing a donor heart that is an excellent match for the recipient, too. “Plus,” said Rosenthal, “there is some likelihood that a small proportion of patients’ hearts will be able to recover and those children will avoid transplant completely.”

TJ and his medical team aren’t sure if or when he will ultimately move toward getting a heart transplant. But he’s been accepted to San Jose State University to study civil engineering, so he may be in class in the fall with his VAD battery pack at his side.

Previously: Packard Children’s heart transplant family featured tonight on Dateline, Liberated from LVAD support: One patient’s story and Pediatric social worker discusses the emotional side of heart transplants
Photo courtesy of Lucile Packard Children’s Hospital Stanford

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