The Neuropathology of Autism

Abstract

Autism is a behaviorally defined neurodevelopmental disorder that affects over 1% of new births in the United States and about 2% of boys. The etiologies are unknown and they are genetically complex. There may be epigenetic effects, environmental influences, and other factors that contribute to the mechanisms and affected neural pathway(s). The underlying neuropathology of the disorder has been evolving in the literature to include specific brain areas in the cerebellum, limbic system, and cortex. Part(s) of structures appear to be affected most rather than the entire structure, for example, select nuclei of the amygdala, the fusiform face area, and so forth. Altered cortical organization characterized by more frequent and narrower minicolumns and early overgrowth of the frontal portion of the brain, affects connectivity. Abnormalities include cytoarchitectonic laminar differences, excess white matter neurons, decreased numbers of GABAergic cerebellar Purkinje cells, and other events that can be traced developmentally and cause anomalies in circuitry. Problems with neurotransmission are evident by recent receptor and binding site studies especially in the inhibitory GABA system likely contributing to an imbalance of excitatory/inhibitory transmission. As postmortem findings are related to core behavior symptoms, and technology improves, researchers are gaining a much better perspective of contributing factors to the disorder.

Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism

“…Our study provides novel evidence that altered expression of parvalbumin is another neuropathological feature of the cerebellum in individuals with ASD. It is well established that the cerebellum is a major locus of neuropathology in autism [reviewed in Blatt, ; Fatemi et al, ]. Early cerebellar damage/injury has been reported to be a very high risk factor for ASD [Limperopoulos et al, ; see Wang, Kloth, & Badura, for review].…”

The basolateral amygdala γ‐aminobutyric acidergic system in health and disease

“…Indeed, in a fragile X mental retardation 1 ( FMR1 ) gene KO model of fragile X syndrome, the total number of neurons, including GABA‐immunopositive interneurons in the BLA, was unaffected. Similarly, human studies of autistic children have shown little morphological alterations in the BLA compared with developmentally typical children (for review see Blatt, ). However, there appears to be a significant decrease in the total number of BLA inhibitory synaptic connections, indicating aberrant circuit development (Olmos‐Serrano et al, ).…”

Endocannabinoid Signaling in Autism

“…Altered neurodevelopment during early pregnancy represents the neuropathological cause of ASD [53,54]. Postmortem studies have unveiled neuroanatomical and cytoarchitectonic abnormalities in the cerebellum, inferior olivary complex, deep cerebellar nuclei, hippocampus, amygdala, entorhinal cortex, fusiform gyrus, and anterior and posterior cingulate cortex, with thinner cortical minicolumns, excessive growth of the frontal lobes, and excessive dendritic spine density [55]. These abnormalities are suggestive of derangements occurring during the first/second trimester of pregnancy, namely reduced programmed cell death and/or increased cell proliferation, altered cell migration, abnormal cell differentiation with reduced neuronal body size, abnormal neurite sprouting, and pruning that result in atypical cell-cell wiring.…”