Brain growth across the life span in autism: Age-specific changes in anatomical pathology

Abstract

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has lead to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism there may also be age-specific changes in gene expression, molecular, synaptic, cellular and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies.

Effects of age and symptomatology on cortical thickness in autism spectrum disorders

“…Across these studies, grey matter volumes within frontal and temporal lobes were significantly increased in children and adolescents with ASD compared to typically developing individuals (Bloss & Courchesne, 2007;Carper, Moses, Tigue, & Courchesne, 2002;Courchesne, Campbell, & Solso, 2011;Hazlett, Poe, Gerig, Smith, & Piven, 2006;Kates et al, 2004;Palmen et al, 2005;Schumann et al, 2010). However, volumetric measurements of lobular regions do not provide spatially localized information on grey matter abnormalities.…”

Class I histone deacetylase inhibition ameliorates social cognition and cell adhesion molecule plasticity deficits in a rodent model of autism spectrum disorder

“…Epidemiological studies have also demonstrated teratogen exposure during the first trimester to be significantly correlated with an increased risk of developing ASD (Christianson et al, 1994;Rasalam et al, 2005). The developmental emergence of this condition has been associated with abnormal synapse remodelling arising from dysregulation of synaptic development proteins, including cell adhesion molecule function and glycosylation state Pinto et al, 2010;), that inexorably gives rise to an array of neuroanatomical malformations (Courchesne et al, 2011).…”

Clinical Evaluations on the Diagnosis of Autism

“…Development peaks occur between 2 and 5 years of age, when cranial circumferences are above average and cerebral volume increases, and are followed, in adolescent and adult ages, by reduced cerebral dimension and function (Aylward et al, 2002;Courchesne et al, 2010;Hazlett et al, 2011). The evaluation and monitoring of child development dynamics may be performed using WHO Anthro software (World Health Organization-WHO, 2011), made in accordance with WHO standards (WHO, 2007) for children aged between 0 and 5.…”