Autism is a neurologic disorder of unknown cause that severely disrupts social, cognitive, and language development. While we and other groups have made progress in identifying anatomical abnormalities in the mature autistic brain, there is little direct knowledge of the sites and types of abnormality characteristic of the autistic infant, and no knowledge of subsequent growth changes. Overall goals of our MRI research are to (1) identify anatomical defects in autistic infants and toddlers; (2) determine abnormal patterns of growth from infancy to early childhood; (3) replicate newly discovered anatomical abnormalities in 2.5 to 5 year old autistic patients; and (4) determine abnormal patterns of growth from middle childhood through adulthood by completing analyses of already collected longitudinal MRI data on autistic and normal control subjects. In our funded MRI research, we have identified specific sites and types of structural and growth abnormality in autistic patients ages 29 months through 42 years. Cerebellar vermis and dentate gyrus were both hypoplastic at the earliest ages examined, but only the dentate showed subsequent age-related increase in size. Striking overgrowth of cerebrum, especially its frontal and temporoparietal regions, was seen in the youngest patients, but subsequent growth was negligible. We hypothesize that a surprising and complex pattern of abnormal regional growth emerges very early in autistic development and an best be captured in studies of autistic infants and toddlers, ages not previously studied by us and only examined in one MRI study in the literature. In our proposed research we will use MRI technologies to identify patterns of pathological growth changes in autism from late infancy (18- 30 months) through early childhood. Subject groups will be autistic, normally and mentally retarded non-autistic. We will also obtain similar neuroanatomical information about infants with PDD-NOS, and thereby gain insight into anatomical abnormalities within the wider autism spectrum. To achieve these goals, we will use a prospective diagnosis and longitudinal MRI procedure. Lastly, we will continue the quantitative measurement of our present sample of 220 subjects (children and adults with autism, and normal controls) acquired as part of our current 5 year longitudinal MRI study. Results from the proposed research will provide knowledge of the developmental anatomic phenotype in autism.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-5 (01))
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Hirtz, Deborah G
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Children's Hospital & Res Ctr at Oakland
San Diego
United States
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Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie (2011) Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 1380:138-45
Schumann, Cynthia M; Bloss, Cinnamon S; Barnes, Cynthia Carter et al. (2010) Longitudinal magnetic resonance imaging study of cortical development through early childhood in autism. J Neurosci 30:4419-27
Schumann, Cynthia Mills; Barnes, Cynthia Carter; Lord, Catherine et al. (2009) Amygdala enlargement in toddlers with autism related to severity of social and communication impairments. Biol Psychiatry 66:942-9
Akshoomoff, Natacha; Farid, Nikdokht; Courchesne, Eric et al. (2007) Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. J Autism Dev Disord 37:887-93
Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric (2007) fMRI during natural sleep as a method to study brain function during early childhood. Neuroimage 38:696-707
Bloss, Cinnamon S; Courchesne, Eric (2007) MRI neuroanatomy in young girls with autism: a preliminary study. J Am Acad Child Adolesc Psychiatry 46:515-23
Akshoomoff, Natacha (2006) Use of the Mullen Scales of Early Learning for the assessment of young children with Autism Spectrum Disorders. Child Neuropsychol 12:269-77
Belmonte, Matthew K; Carper, Ruth A (2006) Monozygotic twins with Asperger syndrome: differences in behaviour reflect variations in brain structure and function. Brain Cogn 61:110-21
Courchesne, Eric; Redcay, Elizabeth; Morgan, John T et al. (2005) Autism at the beginning: microstructural and growth abnormalities underlying the cognitive and behavioral phenotype of autism. Dev Psychopathol 17:577-97
Courchesne, Eric; Pierce, Karen (2005) Brain overgrowth in autism during a critical time in development: implications for frontal pyramidal neuron and interneuron development and connectivity. Int J Dev Neurosci 23:153-70

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