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The Journal of Neuroscience, July 14, 2004, 24(28):6392-6401; doi:10.1523/JNEUROSCI.1297-04.2004
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Neurobiology of Disease
The Amygdala Is Enlarged in Children But Not Adolescents with Autism; the Hippocampus Is Enlarged at All Ages
Cynthia Mills Schumann,1 Julia Hamstra,1 Beth L. Goodlin-Jones,1 Linda J. Lotspeich,2 Hower Kwon,2 Michael H. Buonocore,3 Cathy R. Lammers,4 Allan L. Reiss,2 andDavid G. Amaral1,5 1Department of Psychiatry and Behavioral Sciences, Center for Neuroscience and the M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders) Institute, University of California Davis, Sacramento, California 95817, 2Stanford Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, 3Department of Radiology, University of California Davis School of Medicine, University of California Davis Imaging Research Center, Sacramento, California 95817, 4Department of Anesthesia and Pain Medicine, University of California Davis School of Medicine, Sacramento, California 95817, and 5California National Primate Research Center, University of California Davis, Davis, California, 95616
Autism is a neurodevelopmental disorder characterized by impairments in reciprocal social interaction, deficits in verbal and nonverbal communication, and a restricted repertoire of activities or interests. We performed a magnetic resonance imaging study to better define the neuropathology of autistic spectrum disorders. Here we report findings on the amygdala and the hippocampal formation. Borders of the amygdala, hippocampus, and cerebrum were defined, and their volumes were measured in male children (7.5-18.5 years of age) in four diagnostic groups: autism with mental retardation, autism without mental retardation, Asperger syndrome, and age-matched typically developing controls. Although there were no differences between groups in terms of total cerebral volume, children with autism (7.5-12.5 years of age) had larger right and left amygdala volumes than control children. There were no differences in amygdala volume between the adolescent groups (12.75-18.5 years of age). Interestingly, the amygdala in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. Thus, the amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children. Children with autism, with and without mental retardation, also had a larger right hippocampal volume than typically developing controls, even after controlling for total cerebral volume. Children with autism but without mental retardation also had a larger left hippocampal volume relative to controls. These cross-sectional findings indicate an abnormal program of early amygdala development in autism and an abnormal pattern of hippocampal development that persists through adolescence. The cause of amygdala and hippocampal abnormalities in autism is currently unknown.
Key words: Asperger; amygdaloid complex; development; mental retardation; MRI; neuroanatomy
Received April 6, 2004; revised May 24, 2004; accepted May 29, 2004.
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