Unusual brain growth patterns in early life in patients with autistic disorder: An MRI study. Neurology, 57, 245-254

Department of Neuroscience, School of Medicine, University of California, San Diego, La Jolla, USA.
Neurology (Impact Factor: 8.29). 08/2001; 57(2):245-54. DOI: 10.1212/WNL.57.2.245
Source: PubMed


To quantify developmental abnormalities in cerebral and cerebellar volume in autism.
The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable.
Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI-VII than normal controls.
Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

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    • "Recently, a prospective study of sibling infants at risk for ASD reported that infants who later developed ASD had enlarged total cerebral volume as early as 12 months of age [Shen et al., 2013]. This is consistent with many other studies indicating that young children with ASD have brain overgrowth [Amaral, Schumann, & Nordahl, 2008; Courchesne et al., 2001; Hazlett et al., 2005, 2011; Nordahl et al., 2011; Schumann et al., 2010]. The cellular underpinnings of the brain overgrowth during early childhood, however, remain unclear. "
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    ABSTRACT: The Autism Phenome Project is the largest, single site, longitudinal magnetic resonance imaging (MRI) study of young children with autism spectrum disorder (ASD). Previous analyses from this cohort have shown that the children with autism have a total brain volume at time 1 (∼3 years of age) that is 6% larger than typically developing (TD) children. This finding is driven primarily by 15% of the boys with ASD that have disproportionate megalencephaly (ASD-DM) or brain size that is 1.5 standard deviations above what would be expected for the child's height. In the current study, cerebral cortical grey matter volume, thickness, and surface area were assayed from MRI scans of 112, 3-year-old boys with ASD and 50 age-matched TD boys. The boys with ASD-DM (n = 17) were analyzed separately from the boys with normal brain size (ASD-N, n = 95). Previous studies of cortical thickness and surface area for ASD children in this age range have come to diametrically different conclusions concerning the significance of cortical thickness vs. surface area. Current analyses indicate that cortical thickness was comparable across the ASD and TD groups. However, surface area was significantly greater in the ASD group compared to the TD group. This result was driven largely by the children with ASD-DM. Even in the ASD-DM group, not all cortical regions demonstrated increased surface area. These results provide strong evidence that the early cortical overgrowth associated with ASD is due primarily to increased surface area and not to increased cortical thickness. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
    Autism Research 07/2015; DOI:10.1002/aur.1520 · 4.33 Impact Factor
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    • "in the first year of life ( Chawarska et al . , 2011 ; Dawson et al . , 2006 ; Dissanayake et al . , 2006 ; Fukumoto et al . , 2008 ; Gillberg , 2002 ; Lainhart et al . , 2006 ; Mills et al . , 2007 ; Mraz et al . , 2007 ; Rommelse et al . , 2011 ; Webb et al . , 2007 ) , followed by a period of deceleration sometime between 1 and 5 years of age ( Courchesne et al . , 2001 ; Dawson et al . , 2006 ; Lainhart et al . , 2006 ; Redcay & Courchesne , 2005 ; Rommelse et al . , 2011 ) . This deceler - ation continues so that by late adolescence there is very little difference in head size between individuals with ASD and those with typical development . By early adulthood , brain growth appears to slow and decli"
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    ABSTRACT: Head circumference growth in individuals with an Autism Spectrum Disorder (ASD) has been well characterized in the first two to three years of life and reflects a period of acceleration followed by a period of deceleration when compared with their typically developing (TD) peers. While this altered growth trajectory has been consistently found for head circumference, it is less clear if an abnormal growth trajectory also exists across measures of height and weight. Moreover, most studies have focused on infancy and early childhood, and no longitudinal data have been collected in older children with ASD. This review focuses on the physical growth trajectory of individuals with ASD, and proposes that a general growth dysregulation is present in ASD, and that an endophenotype within ASD may exist that is characteristic of extreme overgrowth. Two possible explanations for a general growth dysregulation are suggested: (1) a connective tissue disorder, which is frequently associated with increased height and disproportionate body ratios; and (2) a dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which regulates growth hormones. The existence of a general growth dysregulation, and possible endophenotype, may serve as a potential biological marker in ASD.
    Developmental Review 02/2015; 36. DOI:10.1016/j.dr.2015.02.001 · 3.23 Impact Factor
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    • "Studies investigating head circumference (HC) and MRI brain volume suggest that in the first year of life, there exists a critical period of abnormal total brain growth that subsequently leads to an enlargement in early childhood, which can sometimes persist into adulthood (Courchesne et al., 2001; Hazlett et al., 2005; Schumann et al., 2010). An aberrant trajectory of growth of the amygdala is also found in MRI studies of individuals with ASD, with amygdala enlargement found even at two years of age (i.e., Mosconi et al., 2009). "
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    ABSTRACT: In this article, a variety of neuroimaging methods that have been applied to investigate autism spectrum disorders (ASDs) will be covered, and a review of the latest findings for each will be summarized. Studies that attempt to map identified brain anomalies in individuals with ASD are mapped onto the symptoms, traits, and severity of the disorder.
    Brain Mapping: An Encyclopedic Reference. V, Edited by Editor-in-Chief: Arthur W. Toga, 02/2015: chapter olume 3: Social Cognitive Neuroscience, Cognitive Neuroscience, Clinical Brain Mapping.: pages Pages 1049–1060; Elsevier Inc.., ISBN: ISBN: 978-0-12-397316-0
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