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Mexico Autism Conference Day 3 Recap

Conference Concludes with Presentations on Treatments, Genetics, Brain Development, Epidemiology and Screening Methods
July 09, 2007

Autism Speaks to the World, an International Congress for Autism Research, hosted by Autism Speaks and the Mexican Autism Clinic, A.C. (CLIMA) concluded on July 7 at the Royal Pedregal Hotel in Mexico City. Held from July 5-7, 2007, the Congress promoted awareness, treatment services, and autism research throughout Mexico and the world.

Presentations given during day three of the congress described current treatments for autism; genetics and underlying brain physiology of the disorder; autism epidemiology; screening methods; and range of programs supported by Autism Speaks. (For previous recaps, click here for day one and here for day 2. )

Lawrence Scahill, professor of nursing and child psychiatry at Yale University, opened the day's proceedings with an assessment of several drugs available for autism treatment now. Scahill stated that the number of children with autism who use medication rose from 30 percent in 1993, to 45 percent in 2001. Of that increase, most could be attributed to heightened use of newer antipsychotics, in addition to a more than three-fold rise in prescriptions for serotonin reuptake inhibitors, and a doubling in prescriptions for stimulants such as methylphenadine, better known as Ritalin. However, the drugs' efficacy for treating problems such as hyperactivity, repetitive behavior, or self-injury in patients with autism was not always equal to that seen in patients with other disorders, he reported. For instance, methylphenadine offered at most a 17 percent improvement in hyperactive symptoms among children with autism, compared to a 40 percent improvement among children with attention deficit hyperactivity disorder, he said. What's more that level of improvement was observed only at the highest dose levels, which were not tolerated by 18 percent of patients with autism, compared to just 3 percent of patients with ADHD. Likewise, SRIs provided little efficacy in the treatment of repetitive behaviors, compared to the better results seen in patients with obsessive compulsive disorder. The most compelling results were obtained with the antipsychotic medication respiridol, which produced a more than 50 percent benefit in terms of mitigation of tantrums, aggression, and self injury. However, respiridol also produced substantial weight gain as a side effect, leading Scahill to caution that metabolic side effects should be carefully monitored during use. Scahill also mentioned that his new research will compare respiridol combined with parental training for improvement of daily living skills in autism patients to respiridol use alone.

The next speaker, Pat Levitt, director of the Vanderbilt Kennedy Center for Research on Human Development at Vanderbilt University, pointed out that most of the drugs used in psychiatry today were discovered serendipitously. Knowledge of underlying systems affected in autism should produce more targeted drugs, he said. Along those lines, Levitt described studies that identified a mutation in a gene called MET, which plays complimentary roles in brain, as well as gastrointestinal (GI) and immune system development. Children with autism often reported to present gastrointestinal and immune problems, he said. A simple mutation that substitutes cytosine for guanine in the gene's sequence appears to be correlated with poor connectivity among brain regions in children with autism, he said. But given MET's known role and activities in regulating the immune system, Levitt suggested that MET mutations might impact brain, GI, and immune system in parallel, and possibly increase susceptibility to environmental factors that trigger autism.

Eric Courchesne, a professor of neuroscience at the University of California at San Diego described his influential studies showing that children with autism have enlarged head circumference at six to 14 months of age. Subsequent studies with volumetric imaging, he said, indicated that the brains of two to four year old children with autism are far larger than normal. Much of that abnormal growth is found in the grey and white matter of the frontal lobe, where social and communication skills affected by autism are coordinated, he said. As children with autism mature, Courchesne added, brain overgrowth becomes arrested. Later, he said, brain matter may actually “thin” or become reduced in volume, although this has yet to be confirmed. Courchesne also described his current research studying post-mortem brains of autistic individuals, supported in part by Autism Speaks. Those studies have shown that frontal lobes in the brains of children with autism contain 42% more cells than normal, explaining their profoundly increased weight and size. Because brain cells develop prenatally, Courchesne emphasized that key processes leading to autism likely occur during pregnancy.

Cecilia Montiel-Nava, from La Universidad del Zulia, in Venezuela, described her work coordinating the only large-scale epidemiology study of autism in Latin America. Performed in children aged three to nine years living Maracaibo, which is the largest municipality in Venezuela, that study generated a prevalence rate of 11.2 cases per 10,000 individuals, which is substantially less than the 60 to 70 cases per 10,000 individuals found in replicated studies performed elsewhere. Montiel-Nava suggested that the population from which those numbers were drawn may not be representative of the population at large, however. Moreover, addition of PDD/NOS cases increased the prevalence rate to 36.0 per 10,000, she said. Like Dr. Fombonne who spoke earlier in the week, Montiel-Nava emphasized that epidemiology studies are crucial to determine needs for public health planning. “We're also providing services for the families of patients that we identify,” she said. “For those who benefit, it's the difference between day and night.”

Tony Charman, a clinical psychologist at Institute of Child Health in London, evaluated screening tools for autism, emphasizing their difference with diagnostic methods that are more rigorous. Charman stated that screening tools must be considered both in terms of their sensitivity—meaning the proportion of children they correctly identify as having the disorder—and their specificity, which is the proportion of children identified correctly as not having the disorder. Screening tools used into two major studies were compared: One, in the United Kingdom, used a screening method called Checklist for Autism in Toddlers, or CHAT. The other, in the Netherlands, employed a test called the Early Screening of Autistic Traits, or ESAT. CHAT, used to screen roughly 16,000 toddlers aged 18 months, demonstrated low sensitivity unless administered in a two-stage process—first by parents, then by clinicians. In single-stage evaluations performed by parents alone, the screen missed up to two thirds of cases, he said. ESAT results proved inconclusive, in part because a third of parents opted out of the study, possibly because age of child assessment was too young, at 14 months. Charman emphasized that screening tool selection should balance needs with the consequences of false-positive or false-negative results. For instance, school audits might tolerate false positive results better than other screens designed to identify children for further evaluation, which can be expensive and anxiety provoking for parents, he said.

Finally, Clara Lajonchere and Andy Shih, Autism Speaks' vice president for clinical programs and vice president for scientific affairs respectively, gave overviews of Autism Speaks' programs. Speaking in Spanish, Lajonchere emphasized that while autism affects one in every 150 people in the US, it gets just $30 million in private funding annually and $90 million from the government. Leukemia, on the other hand, which afflicts one in every 25,000, gets more than $235 million in research funds per year. Created in 2005, Autism Speaks now strives to promote a vision of collaboration and information exchange, she said. Those goals are advanced by several key programs; including AGRE, which is a collaborative repository for genetic material used in autism research; the Autism Tissue Program, a brain bank which collects post-mortem brain samples from autism patients; a Clinical Trials Network, which seeks to accelerate studies of key drugs for autism treatment; a treatment portfolio, which advances evidence-based treatment protocols for autism; and an Internet-based system to support autism research worldwide.

Shih concluded with an overview of current and upcoming Autism Speaks projects. “The reason we're here is that you need our help as much as we need yours,” he said. “And the only language that transcends cultural or social customs is science.”