Brain structural abnormalities in young children with autism spectrum disorder

Objective To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children. Methods Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status. Results Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume. Conclusions These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

[1]  T. Kemper,et al.  NEUROANATOMICAL OBSERVATIONS OF THE BRAIN IN AUTISM , 2003 .

[2]  E. Courchesne,et al.  Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI. , 2001, Brain : a journal of neurology.

[3]  E Courchesne,et al.  Development of the hippocampal formation from 2 to 42 years: MRI evidence of smaller area dentata in autism. , 2001, Brain : a journal of neurology.

[4]  N. Minshew,et al.  Posterior fossa magnetic resonance imaging in autism. , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[5]  N. Minshew,et al.  Brain Volume in Autism , 2001, Journal of child neurology.

[6]  J. Piven,et al.  Abnormal Processing of Social Information from Faces in Autism , 2001, Journal of Cognitive Neuroscience.

[7]  M S Buchsbaum,et al.  Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. , 2000, The American journal of psychiatry.

[8]  J B Poline,et al.  Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography. , 2000, The American journal of psychiatry.

[9]  B. Leventhal,et al.  The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism , 2000, Journal of autism and developmental disorders.

[10]  A. Mayes,et al.  Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism , 2000, Neuroreport.

[11]  N. Minshew,et al.  MRI volumes of amygdala and hippocampus in non–mentally retarded autistic adolescents and adults , 1999, Neurology.

[12]  C. Gillberg Neurodevelopmental processes and psychological functioning in autism , 1999, Development and Psychopathology.

[13]  E Courchesne,et al.  Brain weight in autism: Normal in the majority of cases, megalencephalic in rare cases , 1999, Neurology.

[14]  E. Courchesne,et al.  An MRI study of autism : The cerebellum revisited , 1999, Neurology.

[15]  J. Fryns,et al.  The neurobiology of autism. , 1999, Genetic counseling.

[16]  A. Meltzoff,et al.  Neuropsychological correlates of early symptoms of autism. , 1998, Child development.

[17]  Godfrey D Pearlson,et al.  Mesial temporal lobe measurements on magnetic resonance imaging scans , 1998, Psychiatry Research: Neuroimaging.

[18]  A. Bailey,et al.  A clinicopathological study of autism. , 1998, Brain : a journal of neurology.

[19]  S Arndt,et al.  No Difference in Hippocampus Volume Detected on Magnetic Resonance Imaging in Autistic Individuals , 1998, Journal of autism and developmental disorders.

[20]  S. Bradley-Johnson Mullen Scales of Early Learning , 1997 .

[21]  R. Royall,et al.  Improving sterological estimates for the volume of structures identified in three-dimensional arrays of spatial data , 1997, Journal of Neuroscience Methods.

[22]  S. Folstein,et al.  Macrocephaly in children and adults with autism. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[23]  C. Zeanah,et al.  The clinical assessment of attachment in children under five. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  S Arndt,et al.  Regional brain enlargement in autism: a magnetic resonance imaging study. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[25]  C. Lord,et al.  Follow-up of two-year-olds referred for possible autism. , 1995, Journal of child psychology and psychiatry, and allied disciplines.

[26]  J. Piven,et al.  An MRI study of brain size in autism. , 1995, The American journal of psychiatry.

[27]  D R Fish,et al.  Methods for normalization of hippocampal volumes measured with MR. , 1995, AJNR. American journal of neuroradiology.

[28]  E Courchesne,et al.  Cross‐sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalitiGs , 1995, Neurology.

[29]  R. Adolphs,et al.  Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala , 1994, Nature.

[30]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[31]  J. Bachevalier Medial temporal lobe structures and autism: A review of clinical and experimental findings , 1994, Neuropsychologia.

[32]  B. J. Casey,et al.  Quantitative magnetic resonance imaging of human brain development: ages 4-18. , 1996, Cerebral cortex.

[33]  J Townsend,et al.  The brain in infantile autism , 1994, Neurology.

[34]  Anthony Bailey,et al.  Autism and megalencephaly , 1993, The Lancet.

[35]  L. Squire,et al.  Independence of memory functions and emotional behavior: Separate contributions of the hippocampal formation and the amygdala , 1991, Hippocampus.

[36]  C. Lord,et al.  Austism diagnostic observation schedule: A standardized observation of communicative and social behavior , 1989, Journal of autism and developmental disorders.

[37]  J W Murakami,et al.  Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. , 1989, Archives of neurology.

[38]  E. Courchesne,et al.  Hypoplasia of cerebellar vermal lobules VI and VII in autism. , 1988, The New England journal of medicine.

[39]  L. Goldman,et al.  Diagnostic yield of the autopsy in a university hospital and a community hospital. , 1988, The New England journal of medicine.

[40]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[41]  T. Kemper,et al.  Histoanatomic observations of the brain in early infantile autism , 1985, Neurology.

[42]  Y. Hoshino,et al.  Computed Tomography of the Brain in Children with Early Infantile Autism , 1984, Folia psychiatrica et neurologica japonica.

[43]  A R Damasio,et al.  A neurological model for childhood autism. , 1978, Archives of neurology.

[44]  W. F. Vonderhaar A COMPARATIVE STUDY OF PERFORMANCE SCALE IQ'S AND SUBTEST SCORES OF DEAF CHILDREN ON THE WECHSLER INTELLIGENCE SCALE FOR CHILDREN AND THE WECHSLER INTELLIGENCE SCALE FOR CHILDREN-REVISED , 1977 .

[45]  H. Klüver,et al.  An analysis of certain effects of bilateral temporal lobectomy in the rhesus monkey, with special reference to "psychic blindness." , 1938 .