General Hospital (MGH) has identified specific portions of the brain's white matter that are abnormally large in children with autism and developmental language disorder (DLD). The findings confirm that the previously observed overgrowth of white matter occurs after birth and suggest that it may be related to the process of myelination, in which portions of nerve cells called axons are covered with a material called myelin. The report appears in the April issue of Annals of Neurology.

The researchers noted that the factor most closely associated with the areas showing the greatest volume increase is when the axons in those areas myelinate, a key step in maturation that allows nerve impulses to be transmitted properly. In both autistic and DLD patients, the most enlarged areas were those that myelinate latest in normal development and where myelination takes a longer period of time.

"Knowing that white matter is most enlarged in the area that develops myelin latest will help us narrow the time window in which to look for the cause of these problems and should help focus future research," says Martha Herbert, MD, PhD, of MGH Neurology and the Center for Morphometric Analysis, the paper's lead author.

Autism is a serious developmental disorder characterized by a lack of normal social interaction, language abnormalities and repetitive, ritualistic behavior. Many earlier studies have shown that autistic children often have unusually large brains and experience rapid brain growth in the first years of life. This increased brain volume appears to be concentrated in the white matter. Primarily made up of axons - long processes that extend out from brain or other nerve cells - the white matter is located in the interior of the brain, beneath the cerebral cortex which contains the bodies of brain cells.

The same white matter abnormality is found in developmental language disorder, a condition in which language is abnormal but intelligence and behavior are normal. Few studies have measured brain volume in DLD patients,and some have shown increased brain volume in these children as well.

The current study used advanced techniques for analyzing magnetic resonance imaging(MRI) studies to subdivide white matter into distinct regions related to the pathways taken by axon fibers. Imaging studies were made on 63 children - 13 with autism (all boys), 24 with DLD (14 boys, 7 girls), and 29 normal controls (15 boys, 14 girls). The participants were about ages 8 and 9, and all were high functioning, with IQs over 80.

The results showed that in both the autistic and DLD participants, the outer layer of white matter was significantly larger than among controls, while the inner areas were no different from controls. While all portions of the outer layer of white matter were enlarged in autistic participants, the frontal lobe area (behind the forehead) showed the greatest enlargement. White-matter enlargement in the DLD participants was seen in the frontal, temporal (behind the temples) and occipital (back of brain) areas, but not in the parietal lobe (upper, lateral area). Both groups of children showed the greatest white matter enlargement in the prefrontal area, the very front of the brain. Of particular interest, white matter in the corpus callosum, which connects the right and left hemispheres, showed no volume increase.

"Finding a change in these children's brains that occurs after birth may give us better targets for preventing and treating these disorders. If we develop methods for early detection, we may be able to treat these conditions before they get too advanced," says Herbert, an instructor in Neurology at Harvard Medical School.

Herbert's co-authors are senior author Verne Caviness, MD, DPhil, David Ziegler, Nikos Makris, MD, PhD, Joseph Normandin, and David Kennedy, PhD, of the MGH; Pauline Filipek, MD, University of California at Irvine; Thomas Kemper, MD, Boston University School of Medicine; and Heather Sanders, University of Pittsburgh School of Medicine.

The research was supported by grants from the National Institute of Neurological Disorders and Stroke, the Cure Autism Now Foundation, the National Institutes of Health, the Human Brain Project, the Fairway Trust, and the Giovanni Armenise-Harvard Foundation for Advanced Scientific Research. Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

This story has been adapted from a news release issued by Massachusetts General Hospital.
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