Parent training boosts medication effect for autism [Updated]

Life with a child who has a pervasive developmental disorder such as autism or Asperger's syndrome is often a storm of tantrums, irritability, impulsive behavior and obstinacy — a challenge that has child psychiatrists casting about for ways to help the stressed-out families of their patients, as well as the patients themselves. 

The antipsychotic medication risperidone is approved for those with autism to reduce irritability, and many other medications are widely used to rein in the defiance and explosive behavior that often come with a PDD diagnosis. But a group of researchers, spurred by the National Institute of Mental Health, set out to see if parent training could help children already on medication to further temper their negative behaviors, and bring an added measure of peace to their families.

Compared with kids on medication alone, the behavior of children whose parents got a battery of training sessions improved more and by several measures. The success of the program prompted the authors of the study — researchers from Ohio State University, Indiana University, Yale University and the University of Pittsburgh as well as with NIMH — to declare they will make the parent-training manual, homework assignments and therapist scripts broadly available. Their study is published in the Journal of the American Academy of Child & Adolescent Psychiatry. [Updated 5:45 p.m. Nov. 24] (An earlier version of this article included an incorrect name for this publication. It now has the correct name.)

"Because parents are the agents of change, parent training is less expensive than many other forms of psychosocial intervention," the researchers concluded. The growing population of kids with PDD, they added, makes the availability of "effective behavioral interventions" an urgent need.

Over 24 weeks, the parents of children with pervasive developmental disorder attended as many as 17 sessions, 60 to 90 minutes long, aimed at teaching them to help the child acquire and consolidate self-management and communication skills and to be more flexible and compliant. Parents learned to use visual schedules to ease transitions, to use positive reinforcement effectively, to teach their kids how to communicate their needs and be more flexible. A behavior therapist came to the home twice and made two telephone calls to answer questions and give support. 

— Melissa Healy

Do these genes make my heart seem big? Study finds a gene for empathy

In the long-running nature-nurture debate over what makes us who we are, chalk up a new victory for nature.

A study published Monday in the Proceedings of the National Academy of Sciences has found a single coding variation in the human genome that appears responsible, at least in part, for individual variations in such personality and behavior traits as empathy and response to stress. 

The gene they looked at -- the OXTR gene -- carries the design and production blueprint for cells scattered throughout the heart, uterus, spinal cord and brain that serve as docking stations for a chemical called oxytocin.

Scientists have long known oxytocin as the chemical of bonding and nurture. Produced in the hypothalamus and pumped into both the brain and the bloodstream, oxytocin responds to warm human interaction and drives us to seek it out when our stores are low. It is thought to cause the letdown of milk in breastfeeding mothers, and to soar for many after lovemaking. At the same time, oxytocin appears to have a pronounced calming effect: people and mice alike seem to chill out when the chemical is puffed up their noses or pumped into their bloodstreams, even under conditions of stress.

These two qualities prompted research psychologists from Oregon State University and University of California Berkeley to ask themselves: If some people's genetic endowment made them richer in oxytocin receptors, might they not, by nature, be more attuned to others and more unflappable when under stress?

In the massively complex human genome, it's a daunting challenge to find a single site where a tiny variation in the code of inheritance might produce observable differences in behavior. Fortunately, the authors of the PNAS study had a few clues to guide them: Researchers had earlier found a site on the OXTR gene where certain variations brought with them a higher incidence of autism -- a disorder marked by impairments in social interaction and communication. Variations in this site also had been shown to predict how sensitively mothers responded to their offspring. Perhaps, they asked, coding variations at this same site would yield more subtle differences in a person's sociability and ability to withstand stress?

To make a long story short, they did. The researchers put 192 college students at UC Berkeley through a pair of experimental tests -- one that measured their ability to infer the emotional state of others from looking at their facial expressions and another that measured their jumpiness when warned that a loud blast of noise was imminent. The students also were asked to rate their own levels of empathy and ability to handle stressful situations.

The one in four subjects who inherited a variation in this allele called G/G were significantly better at accurately reading the emotions of others by observing their faces than were the remaining three-quarters of subjects, who had inherited either a pair of A's or an A and a G from their parents at this site. Compared to the three-fourths with A/A or A/G variations, the G/G individuals were also less likely to startle when blasted by a loud noise, or to become stressed at the prospect of such a noise. And by their own reports, the G/G subjects were mellower and more attuned to other people than were the A/As or A/Gs.

The group's findings would appear to strike a decisive blow for nature over nurture in shaping who we are and how we behave. In fact, subjects were asked to rate how nurturing their own parents were, and researchers found that a subject's genetic inheritance seemed a better predictor of his empathic disposition than did his mother and father's parenting styles.

But UC graduate student Laura R. Saslow, a co-author of the paper, cautioned that genetic inheritance -- nature -- is never the sole determinant of our personalities. While researchers will get closer to filling in the inborn components of our personalities, the environments in which we've been raised will always interact with our genetic inheritance and shape how it expresses itself, Saslow says.

"Really, both matter," says Saslow.

-- Melissa Healy

  

Mercury levels not higher in children with autism

The blood levels of mercury are similar in children who are developing normally and children with autism, researchers reported today, and do not appear to be contributing to developmental problems.

The study, reported in the journal Environmental Health Perspectives, is part of a dedicated effort by scientists to identify and study possible causes of autism, both environmental and genetic. The study participants are children between ages 24 months and 60 months who are diagnosed with autism as well as children with other developmental disabilities, and children who are developing normally.

The study examined sources of mercury from fish consumption, personal-care products, vaccinations and dental fillings. Researchers found fish consumption was the biggest and most significant predictor of blood-mercury levels. However, the children with autism appeared to have much lower blood-mercury levels than the children who were developing normally. The lower levels may be due to the observation that children with autism are picky eaters and may eat less fish. When controlling for the difference in fish consumption, however, the two groups had similar levels of blood mercury.

The study, however, did not examine whether mercury plays a role in causing autism because mercury was measured after the diagnosis was made.

"The bottom line is that blood-mercury levels in both populations were essentially the same," said the lead author of the study, Irva Hertz-Picciotto, a researcher at the UC Davis, MIND Institute, in a news release. "However, this analysis did not address a causal role, because we measured mercury after the diagnosis was made.

"It's time to abandon the idea that a single 'smoking gun' will emerge to explain why so many children are developing autism. The evidence to date suggests that, without taking account of both genetic susceptibility and environmental factors, the story will remain incomplete."

-- Shari Roan

Autism's genetic roots examined in new government-funded study

Researchers at Harvard University and Children's Hospital Boston will sequence the genomes of at least 85 people diagnosed with autism in a bid to tease out the genetic basis for some cases of the neuropsychiatric disorder.

Funded by $4.5 million from the federal stimulus package, the study's broad outlines were unveiled Wednesday.

The study's first phase will focus on 85 autistic patients from the Middle East. All have a recessive form of the disease, and all are linked by common ancestry. Studying this unique population, researchers have already narrowed the hunt for the common genetic mutation they share to an area that represents just 1% of their genome.

The Boston researchers hope to extend their genomic analyses beyond the 85 Middle Easterners to include American families as they refine their gene-hunting techniques.  An "informatics" lab at Children's Hospital Boston will compare the genetic profiles culled from autistic subjects to stored genetic data on normal, healthy controls in order to find a needle -- or needles -- in a haystack: any genetic variations that might cause or boost the risk of autism.

Autism affects roughly one in 150 children, according to the Centers for Disease Control and Prevention. But many researchers and activists believe the disorder is becoming more prevalent, and the cause of that growth has sparked heated debate across the country. The condition frequently runs in families, and scientists consider it the most heritable of the neuropsychiatric disorders.

Still, studies of autism in the population find that genes can account for no more than 15% of the numbers of autism cases seen.  

The rest are as yet unexplained. Many argue that environmental exposures -- in particular, to preservatives used in certain vaccines -- are a key factor in the development of autism. But a wide range of comprehensive investigations has failed to find such a link.

-- Melissa Healy

The vaccines-autism debate: on 'Dateline' this Sunday

If you just can't get enough of the vaccines-cause-autism debate, check out "Dateline" this Sunday (Aug. 30), when NBC's Matt Lauer will interview Dr. Andrew Wakefield, whose 1998 medical study was the first to suggest a possible link between the MMR vaccine and autism.

That study, published in the Lancet, was later the subject of controversy, and in 2004, 10 of the paper's 13 authors retracted their names from the report. Wakefield stands by his data and some parents of children with autism are staunch supporters of his theory.

Also featured on the program will be two people with points of view very different to Wakefield's: Brian Deer, a British investigative journalist who wrote in the Sunday Times of London that Wakefield's data may have been falsified, and pediatrician/vaccine expert Dr. Paul Offit, author of the book "Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure."

"A Dose of Controversy"  airs at 4 p.m. PT.

-- Lori Kozlowski

Related links:

Bringing science back into America's sphere

'Bringing science back into America's sphere' hits a nerve

Age of Autism

Respectful Insolence blog

Photo: Tim Sloan / Getty Images

Autism and the gut: no real link after all?

Many parents of autistic children say that their kids seem to have gut disturbances. And many try diets -- such as ones free of gluten or casein -- in the hope that their kids will fare better. The gut-autism link was heavily promulgated by Dr. Andrew Wakefield of the UK, who hypothesized that the MMR vaccine causes problems for the gut as well as the mind in children, resulting in autism. (Wakefield's research has been discredited.)

A Mayo Clinic study published in Pediatrics now reports that the frequency of gut disturbances is no higher in children with autism than in the general population. Read a New York Times article about the issue here.

Here's one doctor's opinion on such diets.

Your thoughts/experiences?

-- Rosie Mestel

Skeptical about hyperbaric chambers for autism? You and Do'C

Healthy Skeptic reporter Chris Woolston noted recently that hyperbaric chambers are becoming, if not the must-have accoutrement for the wealthy health-seeker, at least something of a fad in such circles.

The prospect of slowing or reversing aging is one big draw. Others hope the little extra air pressure and oxygen a chamber provides can cure their cancer or some other chronic disease. In recent years, a growing number of parents have sought hyperbaric therapy to treat their children's autism or cerebral palsy.

Here's Woolston's story: Portable hyperbaric chambers: An expensive folly?

Now Autism Street blogger Dad Of Cameron (a.k.a. Do'C) weighs in with his own reporting:

I'm a science blogging skeptic myself and have written about this so-called "treatment" in considerable detail.... I've provided a roundup of some good skepticism on the subject.

Here's his post: Mild HBOT for autism - a brief skeptical guide.

Skeptics always welcome. (Note: Those who contend that the Earth is flat or the moon landing was staged fall under a different category.)

-- Tami Dennis

Autism researcher: 'Time to start looking' at the environment

Researchers at the UC Davis M.I.N.D. Institute have concluded that the seven- to eightfold increase in the number of children with autism born in California since 1990 cannot be explained by changes in how the condition is diagnosed or how statistics are gathered. Instead, the study, published in the current issue of the journal Epidemiology, suggests research on the cause of the neurodevelopmental disorder should shift to the environment.

"It's time to start looking for the environmental culprits responsible for the remarkable increase in the rate of autism in California," a co-author of the paper, Irva Hertz-Picciotto, said in a news release. "Right now, about 10 to 20 times more research dollars are spent on studies of the genetic causes of autism than on environmental ones. We need to even out the funding."

Hertz-Picciotto, an autism researcher and professor of environmental and occupational health and epidemiology, said the study is important because many researchers, state officials and advocacy organizations have been skeptical of the autism statistics in California. The incidence of autism in the state has increased from nine in 10,000 children (diagnosed by age 6) in 1990 to more than 44 in 10,000 for children born in 2000. The study was conducted using state health records as well as Census Bureau statistics, state birth certificates and vital statistics. The researchers correlated the cases of autism with birth records and excluded children not born in California. They calculated the rate of incidence in the population over time and examined the age of diagnosis.

The study concluded that migration was not the cause of the increase. In addition, inclusion of milder cases of autism only accounted for one-tenth of the increased number of cases. Only 24% of the increase could be attributed to an earlier age of diagnosis.

The M.I.N.D. Institute is currently conducting a study to look at the possible effects of metals, pesticides and infectious agents on neurodevelopment. "If we're going to stop the rise in autism in California, we need to keep these studies going and expand them to the extent possible," Hertz-Picciotto said.

Another study published recently suggests better ways to diagnosis autism may be on the horizon. Early diagnosis and treatment is considered crucial for the optimal development of children with autism. However, no diagnostic tests exist. Children are usually diagnosed using rating systems or checklists. The Centers for Disease Control and Prevention has fact sheets on  autism screening and early signs of the disorder to encourage early diagnosis. However, Italian researchers say they hope babies can be screened for the disorder by using more objective measures.

The study, published in the December issue of the Journal of Proteome Research, found abnormal proteins in the saliva of autism patients that could eventually provide a clue for the molecular basis of the disorder and a marker for a subgroup of patients with autism. The researchers discovered that at least one of four proteins in 19 children with autism had significantly lower levels of phosphorylation, a process that allows proteins to function normally.

-- Shari Roan

Why a malaria vaccine?

The RTS,S vaccine against malaria featured in a Times article today is the closest to possible licensure and use, but it's not the only malaria vaccine candidate. Studies on several others that have also advanced to human trials were presented Monday at a meeting of the American Society of Tropical Medicine and Hygiene underway in New Orleans.

One, under development by the U.S. Naval Medical Research Center and the biopharmaceutical company GenVec Inc., is a genetic vaccine, a newer technology than the protein-based RTS,S. It uses genes found in the DNA of the malaria parasite and delivers them via a de-activated cold virus, prompting the production of antibodies as well as another type of immune reaction called a cell-mediated response.
Another, from the U.S. Military Vaccine Program and the biotech firm Sanaria Inc., is a vaccine that uses an injection of live but weakened malaria parasites to provoke an immune response, much like the measles or mumps vaccines do.

More than one type of vaccine may be needed to beat back malaria, according to Dr. Carlos C. "Kent" Campbell, a longtime director of the malaria program at the national Centers for Disease Control and Prevention. The mosquito-borne parasite that causes malaria is wily. Like HIV, the AIDS-causing virus, it mutates and evades the immune system.

Like many parasites, Plasmodium falciparum also has a complex life cycle, existing in different stages in the liver and bloodstream, making it difficult to target. There is, in fact, no licensed vaccine against any human parasitic disease. Decades of failures have fueled considerable skepticism among malaria experts about whether a vaccine is even possible.

What is not in dispute is that a malaria vaccine is needed, even with the impressive success of insecticide-treated bed nets over the last two years. Campbell pointed out that only one class of insecticide now exists to treat bed nets. So when mosquitoes develop resistance -- and they inevitably will -- gains such as the impressive 69% reduction in severe malaria cases that Zambian health officials announced at this conference could disappear.

Malaria researchers are passionate advocates of vaccines -- especially when confronted with the vocal vaccine critics that have arisen after a controversial paper, since refuted in numerous scientific studies, suggested that the measles vaccine could cause autism. Today's article on RTS,S, for example, has generated e-mail accusations that African children are being used as guinea pigs.

The original guinea pigs were volunteers like Dr. Thomas L. Richie, a U.S. Navy captain who directs the naval research center's malaria program. He and fellow researchers, along with White House policy wonks,  doctors from the National Institutes of Health and other volunteers, not only received the first innoculations but agreed to be stung by malaria-carrying mosquitoes to see whether the vaccine worked.
"Vaccines are always accepted when the horror of the disease is in front of us," Richie said. "We grew up not seeing measles, never seeing diphtheria."

In the early 1900s, he said, diphtheria swept through New England towns, killing a quarter of grade-school-age children within two weeks. The horror of malaria is still very much at the front in  sub-Saharan Africa, where 90% of the estimated 1 million deaths occur each year, most of them among  children under age 5.

-- Mary Engel

Link found between autism and rainfall

Deepening the mystery surrounding the causes of autism, researchers have found a link between high levels of precipitation and increased rates of autism -- a disorder that affects one in 150 American children.

In a study to be released today in November's Archives of Pediatric and Adolescent Medicine, Cornell University economist Michael Waldman found that in areas of California, Oregon and Washington that experienced high levels of rain and snowfall during the years 1987-2001, autism rates among school-aged children rose when measured in 2005. Those children diagnosed with autism would have been under 3 during the periods of high precipitation, the period during which autism is generally diagnosed.

Both Waldman and Dr. Noel S. Weiss of the University of Washington, Seattle, who wrote an editorial about the study in the Archives, cautioned that the findings are very preliminary and stressed that they opened a world of possible explanations for autism besides rainfall itself. High levels of precipitation could mean kids spend more time indoors exposed to household toxins such as cleaning products, or watching TV. Both are hypothesized factors in the development of the disorder. The kids could spend less time in the sunshine, suppressing their bodies' production of Vitamin D, Waldman suggested. Or the link could suggest a more direct role of rainfall in giving rise to autism, he wrote, washing some toxin into drinking water or something else to which children are exposed.

Weiss suggested that the data from which Waldman drew his autism statistics could be unreliable, as diagnoses and records of those diagnoses vary from state to state and county to county.

-- Melissa Healy