The Early Origins of Autism

Rodier, P.M. (February 2000). The Early Origins of Autism. Scientific American.

Miller and Stromland made a surprising observation that 5% of thalidomide victims had autism, a rate about 30 times higher than the rate among the general population. This suggested that autism originates in the early weeks of pregnancy when the nervous system is just beginning to develop. Examining these victims' specific malformations indicated that their development had been impacted about 20-24 days into gestation, before many pregnant women even know they are pregnant. This was way earlier than investigators would have guessed, since very few neurons are even formed by the 4th week. However, most are the motor nerves of the cranial nerves in the brain stem. And indeed, many subjects with autism exhibit abnormalities of eye movement and lack of facial expression, consistent with this observation.

However, it is more likely that these early brain injuries affect more than just the function of the cranial nerve, and may interfere with proper development or wiring of other brain regions in turn. People with autism consistently show a reduction in the number of neurons in the cerebellum of the brainstem, a structure typically thought to involved in fine motor control but also seen activated during certain tasks requiring high-level cognitive processing. Some people with autism also display marked decreases in the facial nucleus (controls muscles of facial expression) and superior olive (a relay station for auditory information). Interestingly, "knock-out" mice engineered to lack the expression of the gene known as Hoxa1 (active when brainstem neurons are forming), show all of these symptoms. While variant alleles of Hoxa1 have been identified, these are only one of many genes involved in the spectrum of autism disorder. Other genes must be found which also increase the risk (or decrease the risk) of developing the disorder.