Abstract
Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits.
Highlights
The clinical diagnosis of autism is currently based primarily on the observation of delayed or disrupted development of social and communication skills; of restricted, repetitive, and stereotypical patterns of behavior, interests, and activities; and having an onset prior to 3 years of age [1]
The first aim of this study was to test the hypothesis that autism is associated with global developmental alterations of neuronal growth including subcortical structures, hippocampus, archicortex, cerebellum, and brainstem
The second aim of this study was to characterize the differences between the trajectories of neuronal growth in (a) children, teenagers/young adults, and adults diagnosed with autism, and (b) age-matched control individuals
Summary
The clinical diagnosis of autism is currently based primarily on the observation of delayed or disrupted development of social and communication skills; of restricted, repetitive, and stereotypical patterns of behavior, interests, and activities; and having an onset prior to 3 years of age [1]. Autism does not have defining neuropathological diagnostic criteria, but smaller than normal neuron size has been reported in qualitative and quantitative studies. Casanova et al [3] reported reduced size of neurons in the frontal and temporal cortex of autistic subjects. Reduced perikaryon volume of pyramidal neurons in the inferior frontal cortex in Brodmann areas 44 and 45 of autistic subjects [4], and in layers V and VI in the fusiform gyrus [5] support the hypothesis of the link between abnormal neuronal growth in some cortical regions and autism functional alterations. The amygdala is involved in processing of social information and emotional interpretation, as well as fear and anxiety [6,7,8]
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