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A proliferation of connections between billions of neurons occurs in all children, of course. A child's brain, unlike a computer, does not come into the world with its circuitry hard-wired. It must set up its circuits in response to a sequence of experiences and then solder them together through repeated neurological activity. So if Courchesne is right, what leads to autism may be an otherwise normal process that switches on too early or too strongly and shuts off too late--and that process would be controlled by genes.
Currently Courchesne and his colleagues are looking very closely at specific genes that might be involved. Of particular interest are the genes encoding four brain-growth regulators that have been found in newborns who go on to develop mental retardation or autism. Among these compounds, as National Institutes of Health researcher Dr. Karin Nelson and her colleagues reported last year, is a potent molecule known as vasoactive intestinal peptide. VIP plays a role not only in brain development but in the immune system and gastrointestinal tract as well, a hint that other disorders that so frequently accompany autism may not be coincidental.
The idea that there might be early biomarkers for autism has intrigued many researchers, and the reason is simple. If one could identify infants at high risk, then it might become possible to monitor the neurological changes that presage the onset of behavioral symptoms, and someday perhaps even intervene in the process. "Right now," notes Michael Merzenich, a neuroscientist at the University of California, San Francisco, "we study autism after the catastrophe occurs, and then we see this bewildering array of things that these kids can't do. What we need to know is how it all happened."
The genes that set the stage for autistic disorders could derail developing brains in a number of ways. They could encode harmful mutations like those responsible for single-gene disorders--cystic fibrosis, for instance, or Huntington's disease. They could equally well be garden-variety variants of normal genes that cause problems only when they combine with certain other genes. Or they could be genes that set up vulnerabilities to any number of stresses encountered by a child.
A popular but still unsubstantiated theory blames autism on the MMR (measles, mumps and rubella) vaccine, which is typically given to children at around 15 months (see box). But there are many other conceivable culprits. Researchers at the University of California at Davis have just launched a major epidemiological study that will test the tissues of both autistic and nonautistic children for residues of not only mercury but also PCBs, benzene and other heavy metals. The premise is that some children may be genetically more susceptible than others to damage by these agents, and so the study will also measure a number of other genetic variables, like how well these children metabolize cholesterol and other lipids.