Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. Proc Natl Acad Sci USA

Department of Psychiatry and Behavioral Sciences, Medical Investigation of Neurodevelopmental Disorders Institute, UC Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2011; 108(50):20195-200. DOI: 10.1073/pnas.1107560108
Source: PubMed


Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4-6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism.

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    • " phantom was used to derive a 3D image distortion map for each child ' s MRI scan . Distortion correction was carried out on all T1 - weighted images to adjust for hardware - induced var - iation , which has been recognized as an important source of error [ Fox & Freeborough , 1997 ] . These proce - dures have been described in detail previously [ Nordahl et al . , 2011 , 2012 ] ."
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    • "A more established picture began to emerge with respect to macro-level measures of brain size, as indexed by measures such as head circumference, brain weight, and magnetic resonance imaging measures of grey and white matter volume. Here data have been presented to suggest larger brain size early in development in ASD compared to controls, characterized as brain 'overgrowth', but a pattern that changes across development, such that by adolescence and adulthood, brain sizes may be smaller than controls (Nordahl et al., 2011; Redcay & Courchesne, 2005; Schumann, Bloss, Carter Barnes, Wideman, Carper et al., 2010; though see Raznahan, Wallace, Antezana, Greenstein, Lenroot et al., 2013, for methodological cautions with respect to population head size norms; Davis, Keeney, Sikela & Hepburn, 2013, that the relationship between head size and disorder is only found in families with a single child with ASD; Nordahl et al., 2011, that larger head size is associated with regressive sub-type of ASD). However, the robustness of early head size differences has recently been questioned. "
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    Full-text · Article · Apr 2015 · Developmental Science
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    • "ces in HC or brain size were found in the female participants . Boys without regressive autism did not differ in HC from TD boys at birth , but diverged from the TD boys and ASD boys with regressive autism between 4 and 6 months of age . Brain volume continued to be abnormally large between 2 and 4 years of age in the boys with regressive autism ( Nordahl et al . , 2011 ) . These results most likely differ from previous studies due to the much larger sample size , comprehensive diagnostic assessments , and the availability of HC data in conjunction with brain volume data obtained via MRI . Gillberg ( 2002 ) provided further evidence that head growth trajectory may differ within ASD . He measured the he"
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