Abstract
IntroductionA total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. The volume of cytoarchitectonic subdivisions, neuronal numerical density, and total number of neurons per region of interest were determined in 14 subjects with autism and 14 age-matched controls by using unbiased stereological methods.ResultsThe study revealed that significant differences between the group of subjects with autism and control groups are limited to a few brain regions, including the cerebellum and some striatum and amygdala subdivisions. In the group of individuals with autism, the total number and numerical density of Purkinje cells in the cerebellum were reduced by 25% and 24%, respectively. In the amygdala, significant reduction of neuronal density was limited to the lateral nucleus (by 12%). Another sign of the topographic selectivity of developmental alterations in the brain of individuals with autism was an increase in the volumes of the caudate nucleus and nucleus accumbens by 22% and 34%, respectively, and the reduced numerical density of neurons in the nucleus accumbens and putamen by 15% and 13%, respectively.ConclusionsThe observed pattern of developmental alterations in the cerebellum, amygdala and striatum is consistent with the results of magnetic resonance imaging studies and their clinical correlations, and of some morphometric studies that indicate that detected abnormalities may contribute to the social and communication deficits, and repetitive and stereotypical behaviors observed in individuals with autism.
Highlights
A total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism
Repeated measures analysis of variance To test the hypotheses that structures differ in the degree to which autism affects, first, the number of neurons in the structure and, second, the volume of the structure, we conducted repeated measures analyses of variance with structure and autistic status as factors, with the potential confounders of brain weight, post-mortem interval, days of fixation, and log age entered as covariates
Estimates of the volume of 38 brain subdivisions, neuronal number per cubic millimeter, and neuronal number per specific cytoarchitectonic subdivision revealed that significant alterations in the group of subjects with autism are limited to the caudate nucleus and nucleus accumbens in the striatum, the lateral nucleus in the amygdala, and Purkinje cells in the cerebellum
Summary
A total of 38 brain cytoarchitectonic subdivisions, representing subcortical and cortical structures, cerebellum, and brainstem, were examined in 4- to 60-year-old subjects diagnosed with autism and control subjects (a) to detect a global pattern of developmental abnormalities and (b) to establish whether the function of developmentally modified structures matches the behavioral alterations that are diagnostic for autism. In the past three decades, numerous studies have been conducted on the trajectory of brain overgrowth, differences between the sizes of individual brain structures and regions, and the abnormal number and size of neurons in the brain in autism spectrum disorder (ASD). Reassessment of evidence of early brain overgrowth revealed that studies using head circumference norms are significantly more likely to identify head circumference abnormalities in ASD than are comparisons between head circumference data of children with ASD and locally recruited control subjects [14]. The authors of this analysis suggest that reports of early brain overgrowth in children with ASD reflect replicable Centers for Disease Control and Prevention norm biases rather than a disease-related phenomenon. There is no doubt that in several genetic syndromes characterized by autistic-like behavior, the brain is enlarged [15], or affected individuals are microcephalic [16,17]
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