Study Shows Autism-related Developmental 'Red Flags' Identifiable At Age Two In Children

Science Daily — Early detection of autism is critical for early intervention, yet autism spectrum disorders (ASD) are typically not diagnosed until after three years of age. However, a study published today in the Journal of Child Psychology and Psychiatry found differences between typically developing children and those with ASD are detectable by two years of age. Because there are currently no medical diagnostic tests for autism, identifying developmental disruptions in infants and very young children with ASD may allow for earlier detection and critical intervention.

The study examined development in 87 infants at 6, 14 and 24 months of age using a standardized development test. Based on data and clinical judgment at 24 months, participants were classified as: unaffected, language delayed (LD) or ASD. Researchers compared development across groups at the three target ages and observed statistically significant differences between the ASD group and the unaffected group at 14 months. By 24 months, significant differences were detectable between the ASD group and both the unaffected and LD groups.

"Introducing behavioral interventions even one year earlier can make a tremendous difference in the lives of children with autism and their families," said Dr. Rebecca Landa, Director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, MD and lead author of the study. "If we are able to educate professionals to identify red flags in development we can then recognize and diagnose the disorder at one-and-a-half or two years of age, instead of three or four, allowing for earlier intervention and ultimately better outcomes."

Participants in the study included infants at high risk for autism (siblings of children with autism), and infants at low risk (no family history of autism). Researchers measured development using the Mullen Scales of Early Learning (MSEL), a standardized test which assesses five domains of development, including: gross and fine motor; visual reception; and receptive and expressive language. At 14 months, four of the five mean MSEL scores were significantly lower in toddlers with ASD than those in the unaffected group. By 24 months, the ASD group performed significantly worse than the unaffected group in all domains of development, and worse than the LD group in three domains. Nearly half of the ASD group showed developmental worsening between 14 and 24 months.

This study and previous research studies conducted by Dr. Landa found that developmental red flags for parents and physicians to watch for include: poor eye contact; reduced responsive smiling; diminished babbling; reduced social responsivity; and difficulty with language development, play and initiating or sustaining social interaction.

"With so many unanswered questions in the autism arena, we need to tackle this condition on many different fronts," said Dr. Gary Goldstein, President and CEO of the Kennedy Krieger Institute. "For this reason, experts at Kennedy Krieger are not only conducting early diagnosis and intervention research, but also investigating the genetic and environmental causes of autism, as well as other potential treatment options."

Autism is the fastest growing developmental disorder in the United States. This year more children will be diagnosed with autism than AIDS, diabetes and cancer combined, yet profound gaps remain in our understanding of both the causes and cures of the disorder. Increasing our knowledge about developmental disruptions in individuals with ASD is crucial, since early detection and intervention can lead to improved outcomes in individuals with ASD.

About the Kennedy Krieger Institute
Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 12,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit www.kennedykrieger.org.

Note: This story has been adapted from a news release issued by Kennedy Krieger Institute.

Mutant Mice Show Key Autism Traits

Science Daily — While the causes of autism remain complex and mysterious, researchers are steadily adding pieces to its intricate puzzle. In what they believe to be a significant new approach to understanding "autism spectrum disorders" (ASD), researchers have developed a mouse that shows abnormal social interactions and brain hypertrophy characteristic of the disease.

In an article in the May 4, 2006, Neuron, Luis Parada and his colleagues report the results of removing (knocking out) a single gene associated with brain disorders in mice. The gene, called Pten, had been associated with a broad array of such disorders when knocked out throughout the animals' bodies. However, Parada and colleagues engineered mice to knock out the gene only in mature, or "postmitotic," neurons of the cerebral cortex and hippocampus in the brain. These regions are associated with higher brain function such as learning and memory.

The mutant mice showed major abnormalities in a variety of social interactions normally undertaken in mice, found the researchers. For example, they were far less likely to approach and sniff new mice introduced into their cage, compared to normal mice. And while normal mice show markedly less interest when such new mice are later reintroduced, the mutant mice did not show such a reduction in interest. This abnormality indicated "impaired social learning or inability to identify the juvenile due to the low level of initial interaction," wrote the researchers.

In other tests of social behavior, the researchers found that--when given the choice of investigating a cage holding another mouse or an empty cage--the mutant mice showed similar preference for the two. Normal mice by far prefer investigating the caged mouse.

The researchers also found the mutant mice to be deficient in nest-forming and sexual and maternal behavior. In tests of their reaction to such sensory stimuli as bright environments, the mutant mice showed hyperactivity and increased anxiety. They also showed sporadic seizures.

The researchers concluded that "the mutant mice exhibited deficits in all social paradigms tested and also showed exaggerated reaction to sensory stimuli, anxiety-like behaviors, seizures, and decreased learning, which are features associated with ASD."

Finally, the researchers found that the mutant mice showed the same kind of abnormal overgrowth of neurons and their interconnections seen in some people with ASD that also show increased brain volume and enlarged heads.

Wrote Joy Greer and Anthony Wynshaw-Boris in a preview in the same issue of Neuron, "caution is warranted because there are aspects of ASD that are not recapitulated in the Pten mutants. For example, the Pten mutants do not display the expression of abnormal repetitive behaviors seen in ASD, although it is unreasonable to expect perfect phenotypic overlap of human ASD with any mouse model."

Also, they wrote, "as appropriately pointed out by the authors, Pten deletion is restricted to postmitotic neurons in the CNS [central nervous system] in their model, and current evidence suggests that ASD is a developmental rather than a neurodegenerative disorder."

Greer and Wynshaw-Boris concluded that "Whether or not the findings . . . have direct relevance to ASD, the experimental results described are intriguing and represent an important entry point to understanding the role of Pten in postmitotic neurons of the hippocampus and cortex as well as providing new insight into the molecular correlates mediating social- and anxiety-related behaviors in the postnatal CNS."

The researchers include Chang-Hyuk Kwon, Bryan W. Luikart, Craig M. Powell, Jing Zhou, Sharon A. Matheny, Wei Zhang, Yanjiao Li, and Luis F. Parada of the University of Texas Southwestern Medical Center in Dallas, TX; Suzanne J. Baker of St. Jude Children's Research Hospital in Memphis, TN. This work was supported in part by the American and Lebanese Associated Charities, NIH grant NS44172 (to S.J.B), and NIH grant R37NS33199 and the American Cancer Society (to L.F.P.).

Kwon et al.: "Pten Regulates Neuronal Arborization and Social Interaction in Mice." Publishing in Neuron, 50, 377-388, May 4, 2006. DOI 10.1016/j.neuron.2006.03.023 www.neuron.org