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UC Davis Autism Study Finds Structural Differences in Brain Areas Regulating Fear

October 10, 2007

Study Highlights the Promise of Neuropathology Research in Autism



Anxiety and a lack of emotional regulation are among the major challenges that individuals with autism face. The amygdala, a part of the brain involved in regulating fear-response, may be part of the impaired physiology of autism, which contributes to these deficits. A new study out of the University of California, Davis/M.I.N.D. Institute by Cynthia Schumann, Ph.D. and CAN Scientific Advisory Board member David Amaral, Ph.D., has shown that there are fewer neurons in the amygdalae of autistic adolescent and adult males than in the amygdalae of individuals without autism. The researchers found that while the autistic group showed no difference in overall volume of the amygdala, they had fewer neurons overall. Moreover, a comparison of the functional subdivisions of the amygdala (nuclei) showed a decreased number of neurons in the lateral nucleus, which modulates sensory processing through direct connections with numerous brain areas.

While it has long been proposed that the amygdala is involved in the pathophysiology of autism (for recent CAN science articles that discuss the amygdala and autism see Research Identifies Gene Involved in Fear-Response Learning and CAN's Science Director Examines Autism's Characteristic Eye Contact Avoidance), the exact nature of the deficit has not been known. In an earlier Magnetic Resonance Imaging study of the amygdala in children and adolescents, Drs. Schumann and Amaral, with their colleagues, demonstrated that autistic children have larger amygdalae than those of children the same age. However, by adolescence, there is no difference in the size of the amygdala between individuals with or without autism. This suggests an early, overactive growth phase in autism which ends in late childhood, a theory that has also been supported by data from other laboratories (To read how this finding relates to our overall understanding of brain size differences in autism see Cure Autism Now Science Summary: Gray Matter Enlargement). Previous post-mortem studies by CAN Scientific Advisory Board member, Margaret Bauman, M.D. and colleagues examined the structure of the amygdala in a small number of individuals and observed smaller cell sizes and increased density of neurons. While these and other studies have been integral to building our knowledge about the size and the general cellular structure of the amygdala in autistic individuals, these studies did not provide information about differences in the actual number of neurons in the amygdala.

This current study is important because it is the first to examine the pathology of the amygdala in autism through an actual count of neurons using an extremely accurate optical technology known as stereology. As such, the study provides direct evidence of a structural deficit in the amygdala, adding an important new piece to our emerging understanding of the possible cellular abnormalities in the amygdalae of autistic individuals. Measuring neuron density (the number of neurons per a certain amount of tissue) can be confounded by the fact that brain tissue shrinks when it is processed for analysis. Dr. Schumann explains, "This is one of the reasons stereology is such a valuable tool. It is an unbiased way of counting neurons that is independent of tissue volume." Studies using this technique can help better characterize the cellular impairments in the amygdalae of autistic individuals. Building on the findings from this study, the researchers propose that future studies could determine if the decreased numbers of neurons is a phenomenon which is due to later cell degeneration resulting in loss of an initially normal or excessive number of neurons, or whether individuals with autism start off with a lower number of neurons early in development.

The findings from current studies are encouraging, but since the number of individuals involved in such studies is still small, continued research in this area is vital. Realizing the critical need for more neuropathological studies to examine in detail the brain abnormalities in autism, earlier this year CAN established a collaborative neuropathology workgroup to directly characterize how the brains of individuals with autism develop. Using similar stereological techniques, researchers from multiple sites will be sharing their time and expertise to analyze the structure of the frontal lobe of the brain in autism. Among the several principle investigators in this new effort are Eric Courchesne, Ph.D. and Katerina Semendeferi, Ph.D. (University of California, San Diego), Carlos Pardo, M.D. (Johns Hopkins University), Karoly Mirnics, M.D. (University of Pittsburgh), and Dan Buxhoeveden, Ph.D. (University of South Carolina). Using the largest group of brains yet assembled for postmortem analyses, the workgroup organized by CAN will be characterizing several parameters, including neuron numbers and the presence of abnormalities in laminar patterns, minicolumns, neuroinflammatory cells, and axonal characteristics. In order to carry this out, the effort also includes important collaborations with the Autism Tissue Program and the New York Institute for Basic Research in Developmental Disabilities on Staten Island. Dr. Schumann, who has since joined the laboratory of Dr. Courchesne, will be continuing her studies on the pathology of the brain as part of this large effort to identify the cellular systems affected in autism.

To read the press release from UC Davis, click on the link:
UC Davis M.I.N.D. Institute Researchers Find Fewer Neurons In The Amygdala Of Males With Autism

To hear the feature on this article on NPR, click on the link:
New Autism Study Shows Discrepancy in Brains

Featured Article:

Schumann C & Amaral D. Sterological analysis of amygdala neuron number in autism. The Journal of Neuroscience. July 19, 2006. 26(29):7674-7679.

References:

Bauman M & Kemper TL. Histoanatomic observations of the brain in early infantile autism. Neurology. 1985. 35:866-874.

Bauman M & Kemper TL. Neuroanatomic observations of the brain in the autism. In Bauman M & Kemper (Eds.). 1994. The Neurobiology of Autism. pp. 119-145. Baltimore: Johns Hopkins UP.

Schumann C, Hamstra J, Goodlin-Jones B, Lotspeich L, Kwon H, Buonocore M, Lammers C, Reiss A & Amaral D. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. The Journal of Neuroscience. July 14, 2004. 24(28):6392-6401.