Neural anomalies

In patients with autism, neuroanatomic and neuroimaging studies reveal abnormalities of cellular
configurations in several regions of the brain, including the frontal and temporal lobes and the
cerebellum. Enlargements of the amygdala and the hippocampus are common in childhood.
Markedly more neurons are present in select divisions of the prefrontal cortex of autopsy
specimens of some children with autism, compared with those without autism.[22]
Magnetic resonance imaging (MRI) studies have suggested evidence for differences in
neuroanatomy and connectivity in people with autism compared with normal controls.
Specifically, these studies have found reduced or atypical connectivity in frontal brain regions, as
well as thinning of the corpus callosum in children and adults with autism and related conditions.
Importantly, some of the regional differences in neuroanatomy correlate significantly with the
severity of specific autistic symptoms.[23, 24] For example, social and language deficits of people
with autism likely are related to dysfunction of the frontal and temporal lobes.[25]
In a study of postmortem brain tissue from 11 children with autism and 11 unaffected controls,
researchers found focal disruption of cortical laminar architecture in the cortexes of 10 of the
children with autism and 1 of the controls, suggesting that brain irregularities in autism may have
prenatal origins. The patches of abnormal neurons were found in the frontal and temporal lobes,
regions involved in social, emotional, communication, and language functions. Since the changes
were in the form of patches, the researchers believe that early treatment could rewire the brain
and improve ASD symptoms.[26, 27]
On MRI scans, the brains of children with autism spectrum disorder demonstrate greater
myelination in bilateral medial frontal cortices and less myelination in the left temporoparietal
junction.[28] Similarly, region-specific differences in the concentrations of gray matter, made up of
neuronal cell bodies, dendrites, unmyelinated axons and glial cells, are also found in the brains of
people with autism.[29]
Postmortem specimens of the brains of people with autism demonstrated reductions for gammaaminobutyric acidB (GABAB) receptors in the cingulate cortex, a key region for the evaluation
of social relationships, emotions, and cognition, and in the fusiform gyrus, a crucial region to
evaluate faces and facial expressions.[30] These findings provide the basis for further investigation
of autism and other pervasive developmental disorders.

Metabolic anomalies
In animal studies, dysfunction of serotonin and the neuropeptides oxytocin and vasopressin has
been associated with abnormalities in affiliative behaviors. Neurophysiologic dysfunction
involving 1 or more of these substances may also be present in humans with autism
Elevations of blood serotonin levels occur in approximately one third of individuals
with autistic disorder and are also reported in the parents and siblings of patients.
Functional anomalies in other neurotransmitters (eg, acetylcholine, glutamate) have
also been identified in some people with autism spectrum disorder. [25, 31]
Serum biotinidase is reduced in some people with autistic disorder. This enzyme is
required for the use and recycling of the B vitamin biotin. Deficiency of biotin has
been linked with behavioral disorders.
Immunologic studies have identified abnormalities such as decreased plasma
concentrations of the C4B complement protein. Such abnormalities may be the
source of the increased susceptibility to infection seen in some people with autism.
Diet is a controversial aspect of autism. The greatest attention has been given to
gluten- and casein-free diets; anecdotal information suggests that these diets help
some children with autism.[32] Test findings suggest that low-functioning children
with autism may have impairment in the metabolism of phenolic amines. [33]
Therefore, symptoms of autistic disorder are possibly aggravated by the
consumption of dairy products, chocolates, corn, sugar, apples, and bananas;
however, no large population studies have confirmed this.
Oxidative stress may play a role in the pathogenesis and the pathophysiology of
autism.[34] Compared with normal children, children with autism have decrements in
the following[34] :

Plasma levels of cysteine, glutathione, and methionine

The ratio of S -adenosyl-L-methionine (SAM) to S -adenosyl-L-homocysteine

(SAH)

The ratio of reduced to oxidized glutathione

Some children with autism display hyperlacticacidemia [35] as well as evidence of

mitochondrial disorders[35] including carnitine deficiency.[36] These abnormalities may
reflect disturbed neuronal energy metabolism.