This manuscript reviews
biological abnormalities shared by
autism spectrum disorder (ASD) and
epilepsy. Two neuropathological findings are shared by ASD and
epilepsy: abnormalities in minicolumn architecture and γ-
aminobutyric acid (
GABA) neurotransmission. The peripheral neuropil, which is the region that contains the inhibition circuits of the minicolumns, has been found to be decreased in the post-mortem ASD brain. ASD and
epilepsy are associated with inhibitory
GABA neurotransmission abnormalities including reduced GABAA and GABAB subunit expression. These abnormalities can elevate the excitation-to-inhibition balance, resulting in hyperexcitablity of the cortex and, in turn, increase the risk of
seizures. Medical abnormalities associated with both
epilepsy and ASD are discussed. These include specific genetic syndromes, specific metabolic disorders including disorders of energy metabolism and
GABA and
glutamate neurotransmission,
mineral and
vitamin deficiencies,
heavy metal exposures and immune dysfunction. Many of these medical abnormalities can result in an elevation of the excitatory-to-inhibitory balance. Fragile X is linked to dysfunction of the mGluR5 receptor and Fragile X, Angelman and Rett syndromes are linked to a reduction in GABAA receptor expression. Defects in energy metabolism can reduce
GABA interneuron function. Both
pyridoxine dependent seizures and
succinic semialdehyde dehydrogenase deficiency cause
GABA deficiencies while
urea cycle defects and
phenylketonuria cause abnormalities in
glutamate neurotransmission.
Mineral deficiencies can cause
glutamate and
GABA neurotransmission abnormalities and
heavy metals can cause
mitochondrial dysfunction which disrupts
GABA metabolism. Thus, both ASD and
epilepsy are associated with similar abnormalities that may alter the excitatory-to-inhibitory balance of the cortex. These parallels may explain the high prevalence of
epilepsy in ASD and the elevated prevalence of ASD features in individuals with
epilepsy.