"A critical mass of scientists and the new tools of molecular biology are deepening our understanding of autism at a breathtaking pace," said Helen Tager-Flusberg, chair of the conference and a professor at the Boston University School of Medicine. "The immune system, behavior, genetics, and the environment all factor in to this complex and devastating disease. We are putting the pieces together."
Among the advances reported by scientists were:
- Early Detection: Identification of both potential biological markers in the blood (biomarkers) and behaviors that will allow scientists and physicians to identify autism in infants, and thus initiate early treatment.
- Immune System: Strong evidence that autism may be a disorder involving the immune system as well as a disorder of the brain.
- Genetics: Studies homed in on chromosomal regions implicated in autism. Exciting results came from looking at autistic-like traits.
- Environment: Scientists documented overlap between environmentally responsive genes and genes associated with autism, and found evidence into the potential role of environmental toxins such as PCBs.
Scientists reported their findings at the 4th International Meeting for Autism Research (IMFAR). The UC Davis M.I.N.D. Institute, Cure Autism Now, and the National Alliance for Autism Research initiated the annual conference, which is the most extensive exploration of research advances in autism.
Scientists reported progress in being able to diagnose the youngest children through both biomarkers and behavioral observations.
"Whereas today most autistic children are not diagnosed until they are two to three years old, detection in infants would allow early treatment, which can profoundly benefit some children with autism," said David G. Amaral, research director at the UC Davis M.I.N.D. Institute. "And, ultimately, finding biological markers in infants may also yield the fastest route to a cure."
Reports on scientific advances in early detection included:
Biomarkers: Amaral reported on a comparison of blood samples from 70 autistic children and 35 same age normally developing children revealed differences in proteins, metabolites and the immune system. These included elevated levels of immune system B cells and natural killer cells in the autistic group, and more than 100 proteins that the two groups expressed differently.
Behavior: Researchers identified a variety of behaviors, some identifiable in the first year of life, that are predictive of autism. Lonnie Zwaigenbaum at McMaster University in Hamilton, Canada, reported that vocal differences at 12 months were predictive of autism in high-risk infants (those with older siblings who have autism, and Sally Rogers of the UC Davis M.I.N.D. Institute and Marian Sigman of UCLA found that at 12 months, high-risk infants are less likely to respond to their own name than low-risk infants. Other predictive behaviors in very young children included abnormalities in gesture, eye contact, body or limb posturing, and atypical sounds and words.
In addition, two studies showed that clinical diagnoses can be made reliably at 14 to 18 months of age. This is a major advance over current clinical practice, which diagnoses children between ages three and four.
Although autism is considered a disorder of the brain, emerging evidence indicates that it may be a disorder of the immune system as well. For instance, a study by Judy Van de Water at the UC Davis Center for Children's Environmental Health and UC Davis M.I.N.D. Institute reported differences in protein molecules called cytokines. The study compared immune cell responses between autistic and typically developing same-age children aged two to five. One difference appeared in response to bacteria, with cells from the autistic group having lower levels of cytokines, which help mediate the body's overall immune response and can also affect mood and behavior. Scientists say the potential connection of cytokines to autism is an intriguing area of research that warrants further investigation.
Autism has a strong genetic component, and estimates are that five to 20 genes are likely involved in the condition. Some of these genes may be responsible for inherited traits that by themselves do not cause autism, but may be associated with it. These traits, called endophenotypes, can be behavioral or biological. Scientists are identifying such traits in the family members of autistic children.
"As we identify endophenotypes and their related genes, such as for language delay, we will be homing in on genes for autism," said Daniel Geschwind of the University of California, Los Angeles, School of Medicine. "This is one of the most exciting developments in the field of autism genetics today."
Scientists at the conference reported on endophenotypic traits such as large head size in family members, parents' abnormal brain processing of faces, and the degree to which relatives of autistic children can read another person's mental state. One recent study by Geschwind and his colleagues validated the importance of endophenotypes in teasing out the genetics of autism. The study identified autism-related regions of the genome in children who are part of the AGRE consortium (the largest publicly available collection of autism families). Using the Social Responsiveness Scale (SRS), an instrument that rates 65 behaviors to measure the severity of a child's symptoms and social impairments, the scientists found that the SRS is a powerful tool to detect genetic loci for autism-related social impairment. Specifically they found evidence supporting the location of genes for autism on chromosomes 11 and 17, as well as in a number of other regions of the genome.
The number of children diagnosed with autism has increased significantly in recent years, leading many scientists to think that non-genetic factors in the environment may be at least partially responsible. Studies that investigated this possibility included:
PCBs and Language Development
Dr. Tal Kenet, Michael Merzenich, and Isaac Pessah at the University of California, San Francisco and Davis, found that rats' exposure to polychlorinated biphenyls (PCBs) showed disturbances in the development of the brain's auditory cortex, but without affecting hearing. However, in humans such brain defects would almost certainly disturb language development in ways typical of autism, the researchers said. The study suggests that environmental factors may combine with genetic predispositions to contribute to the increased incidence of autism.
Environmentally Sensitive Genes Overlap with Genes Associated with Autism
Dr. Martha Herbert at Massachusetts General Hospital found at least 51 overlapping genes when her team compared a scan of the Environmental Genome Project database with published autism genome scans. In addition, children with Autism Spectrum Disorder who possessed alterations within one or more of these 51 genes were likely to exhibit altered susceptibility to environmental toxicants.
Other reported studies evaluated the effectiveness of behavioral treatments; costs of healthcare for children with autism; changes in the prevalence of autism; mental processes behind special skills in autistic people; and brain anatomy and development associated with autism.
"All of these studies reflect only a small snapshot of the wealth of insight and experience being accumulated by today's scientists," Amaral said. "It is heartening for parents, doctors and scientists to see this progress, while also knowing the distance we have yet to go to prevent and treat, and perhaps one day cure, autism."
IMFAR is organized by the International Society for Autism Research, a new professional society that emerged as a result of the conference. Financial support comes from the Autism Society of America, Cure Autism Now, Janssen, the National Alliance for Autism Research and the National Institute of Mental Health.
The UC Davis M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute is a unique collaborative center for research into the causes and treatments of autism, bringing together parents, scientists, clinicians and educators. For further information, go to http://www.