Trends in Neurosciences
ReviewNeuroanatomy of autism
Introduction
Autism is a heterogeneous disorder with multiple causes and courses, a great range in the severity of symptoms, and several associated co-morbid disorders. Increasingly, researchers refer to ‘the autisms’ rather than a single autism phenotype [1]. It would be surprising, therefore, if the neuropathology of autism was identical across all affected individuals.
Section snippets
The core and co-morbid features of autism
As initially described by Kanner [2], individuals with autism have three core features: (i) impairments in reciprocal social interactions; (ii) an abnormal development and use of language; and (iii) repetitive and ritualized behaviors and a narrow range of interests. In addition to the core features of autism, there are common co-morbid neurological disorders [3]. The prevalence of mental retardation in idiopathic autism is ∼60% although, when the autism spectrum is taken as a whole, the number
Where might one expect to see neuropathology?
In Figure 1, we summarize the major brain regions that form the putative neural systems involved in the functions that are most impacted by the core features of autism. Several brain regions have been implicated in social behavior through experimental animal studies, lesion studies in human patients or functional imaging studies [8]. These include regions of the frontal lobe, the superior temporal cortex, the parietal cortex and the amygdala. Language function is distributed throughout several
Experimental techniques
Structural magnetic resonance imaging (MRI) is a safe, relatively noninvasive tool for evaluating gross neuroanatomical changes related to autism. An ideal study would include a very large sample size (i.e. hundreds of subjects) of well-characterized individuals of both genders [14], imaged at birth and followed longitudinally at least into late childhood or early adolescence. The ideal study, however, has not been carried out. Many have been hampered by small sample sizes and virtually all are
Postmortem cortical neuropathology
As discussed above, MRI studies have consistently found increases in brain size in younger children with autism followed by an abnormal growth pattern through adolescence. What does this tell us about the neuropathology of autism? If the brain is larger, are there too many neurons, glia, synapses and so forth? If the difference in brain size does not persist into adulthood, what neuropathological underpinnings account for this phenomenon of an abnormal growth trajectory? With the availability
Neuropathology of the cerebellum
Five MRI studies of individuals with autism at a wide range of ages have found the cerebellum to be enlarged relative to controls [45]. However, this increase in cerebellar volume is generally proportional to total brain volume, with one exception in which the difference exceeded that of the cerebrum [46]. Only one published study to date has examined children younger than age 3, and this study did not find a difference in cerebellar size between the children at risk for autism and typically
Neuropathology of the amygdala
The amygdala (Figure 3) in boys with autism appears to undergo an abnormal developmental time course that includes a period of precocious enlargement that persists through late childhood 21, 25. Sparks et al.[21] found a 13%–16% abnormal enlargement of the amygdala in young children with autism (36–56 months of age). Recent studies suggest that amygdala enlargement is associated with more severe anxiety [54] and worse social and communication skills [55].
Schumann et al.[25] examined the
Other brain regions
The investigation of other brain regions that might be affected in autism (Figure 1) is limited. There is little MRI evidence and no postmortem evidence for abnormalities in the thalamus 61, 62, 63 and basal ganglia 64, 65, 66, 67. There is evidence for enlargement of the caudate nucleus that might be correlated with the presence of repetitive and ritualistic behaviors in adolescents and young adults 64, 65. There is also evidence, although somewhat inconsistent (see Ref. [45] for a review),
Where do we go from here?
Given the enormous heterogeneity in the manifestation of core features of autism spectrum disorders, varied occurrence of significant co-morbid syndromes and generally small sample sizes of both MRI and postmortem studies of autism, it is remarkable that any significant group differences have been detected. It would not be surprising, therefore, if more clear-cut pathology emerges once distinct phenotypes of the disorder are considered as factors in the analyses.
Attempts at defining the
Acknowledgements
The authors have been supported by NIH grants R37 MH057502 and MH41479. C.W.N. was a Fellow of the Autism Research Training Program (T32 MH07134). We would like to thank the following colleagues who read earlier versions of this manuscript and provided helpful advice: Margaret Bauman, Gene Blatt, Manuel Casanova, Joseph Piven, Sally Ozonoff and two anonymous reviewers.
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