The Study Identifies The First Neurobiological, Early-Warning Signs

Small head circumference at birth, followed by a sudden and excessive increase in head circumference during the first year of life, has been linked to development of autism by researchers at the University of California, San Diego (UCSD) School of Medicine and Children's Hospital and Health Center, San Diego. Autism spectrum disorder occurs in one out of every 160 children and is among the more common and serious of neurological disorders of early childhood.
The study identifies the first neurobiological, early-warning signs of autism during a child's first year of life, and offers the potential for earlier diagnosis, intervention and improved clinical outcomes for autistic children. In addition, this dramatic brain overgrowth is expected to become a major focus of future autism genetics research.

The early-warning sign -- abnormally accelerated rate of head, and therefore brain, growth -- occurs well before the first clinical signs of autism. It also appears to predict the severity of clinical outcome as well as the degree of brain abnormality at a later age. Currently, the disorder is not typically detected until ages two to four, when a child develops behavioral signs and symptoms, such as delayed speech, unusual social and emotional reactions, and poor attention to and exploration of the environment.

The investigators noted that this rapid, excessive brain growth in infants with autism does not allow enough time for accumulation of experiences and emotions that guide and shape normal behavior.

"During this period of important learning and plasticity, when the brain is experiencing the world and deciding how to construct itself, it's growing too fast in the infant with autism," says the study's senior author Eric Courchesne, PhD, UCSD professor of neurosciences and director of the Center for Autism Research at Children's. "Without the guidance of experience and learning, the brain may be creating abnormal connections that make it very hard for autistic children to make sense of the world they live in."

The research team also found that the rate of excessive brain growth predicted the severity of autism. Children later diagnosed with a more severe form demonstrated a faster, and greater rate of brain overgrowth during their first year of life, compared to that of children with a milder form of the disorder.

Noting that the new findings offer strategies for earlier diagnosis and treatment, study co-author Natacha Akshoomoff, PhD, said "previous studies have shown that early therapeutic services result in a better outcome for the child. These usually include speech and occupational therapy, plus communication and social skill building. However, currently there are no biological or medical interventions for children identified with autism." Akshoomoff is a UCSD assistant professor of psychiatry, and assistant research scientist at Children's.

In studying the medical records of 48 two- to five-year olds who have been diagnosed with autism spectrum disorders, the research team recruited volunteers from community advertisements and referrals. Each of the children in the study had been a participant in previous MRI studies reporting age-related changes in the brain in autism. The children's head circumference measurements at birth and during various points in their first year of life were compared to the Centers for Disease Control and Prevention growth charts for normal children and to the Fels Longitudinal Study of head circumference in 51 infants born between 1980 and 2001.

It was found that the head size of the autistic children at birth was, on average, in the 25th percentile, meaning that the circumference measurement for these children was smaller than 75 percent of other newborns. During the first year of life, however, these same children experienced sudden, rapid and excessive brain growth, that put them in the 85th percentile at about 12- to 14-months of age. From then on, the brain growth slowed.

"This burst of overgrowth takes place in a brief period of time, between about two months and six to 14 months of age," Courchesne says. "So, we know it cannot be caused by events that occur later, such as vaccinations for mumps, measles and rubella or exposure to toxins during childhood."

Although no one has yet determined the biological cause of autism, the new findings "give us information about the timing of abnormal brain development," says study co-author Ruth Carper, PhD, a post-doctoral researcher in the UCSD Department of Neurosciences and a research associate at Children's. "This provides a timeframe for further research, to determine the exact brain abnormalities and the biological mechanisms which produce them."

"This dramatic brain growth in early life is the first active neuro-developmental process to be discovered in infants with autism," Courchesne adds. "It provides, for the first time, a developmental process to target for animal model studies of the disorder. Animal models that accurately mimic these abnormal growth events will be necessary in order to discover causes and biological treatments for autism. Once we know what causes this specific growth defect, it may be possible to use biological treatments to successfully intervene before the overgrowth begins, thereby allowing the brain and behavior to develop down more normal paths."

Although some conditions, such as hydrocephalus or certain types of metabolic disorders, cause a large head circumference in the first year of life, these clinical conditions are much less common than autism spectrum disorders, which occur in as many as one out of every 160 children. According to the Autism Society of America, more than a million Americans (including adults) suffer from an autistic disorder.

The correlation between rapid brain growth and the behavioral manifestations seen in autistic children was also discussed in study. The three authors noted that "this early, yet transient, period of brain overgrowth must be an important factor in causing the emergence of autistic behavior because it occurs at the beginning of an important period of developmental neuroplasticity and learning."

Research has shown that the developing human brain is designed to benefit from an extended period of experience-guided growth. In the study, the researchers noted that sensations, emotions, thoughts and actions direct the brain's axonal and dendritic growth, creating, reinforcing or eliminating brain synapses as needed. Eventually, these experiences lead to the emergence of refined higher order neurobehavioral functions, such as cognitive, emotional, linguistic and motor skills.

"Using our findings as an early indicator of autism, intervention might begin two or three years earlier when the brain might be at a more malleable stage and so, might result in a better outcome for the child," Courchesne says. And, all it takes is a simple, low-tech tape measure. Unfortunately, not all infants get their head circumference measured on a regular basis, Akshoomoff notes. "Although nearly all hospitals measure a newborn's head circumference, this measurement is sometimes not included in each well-baby visit," she says. "If pediatricians include head circumference measurements routinely throughout the first year of life, and use up-to-date head circumference norms, they might notice a rapid growth, and could then refer the child for thorough diagnostic testing and possible early intervention services." The research team, directed by Courchesne, plans to expand this study to a larger group of children, to better determine the timing of brain mal-development. This will include sophisticated MRI studies that follow children under age three for several years.


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