Autism is largely genetic, but evidence also points to "triggers" in the prenatal environment.
Some experts suspect that the stage is set for autism early in the first trimester, a suspicion rooted in the birth-defect epidemic caused by the morning-sickness remedy thalidomide in the 1960s. Of the babies born with severe limb abnormalities after their mothers took the drug, 5 percent also had autism, about 30 times the expected rate. This points to brain injury between 20 and 36 days after conception, when arms and legs are being formed. In contrast, an Ohio State University study found that women who'd suffered major stress, such as the death of a spouse, between the 24th and 28th weeks of pregnancy had a higher risk of delivering an autistic child.
Evidence also points to prenatal hormone levels: The more testosterone is present in the womb, the more likely a child is to have ASD. And researchers at the Centers for Disease Control and Prevention have noted possible associations with obstetrical complications, including preterm delivery, low birth weight and breech presentation of the baby.
Whenever it begins, the cascade of events that leads to autism probably starts with a genetic vulnerability, most likely with dysfunction in five to 15 genes. "With multiple dysfunctional genes, the child's system becomes susceptible to environmental insult," Pessah says.
Many questions about moms
One focus of current investigation is whether a maternal immune system gone awry could raise the risk of autism. "We've found increased numbers of persons with autoimmune diseases, such as rheumatoid arthritis and lupus, in the families we've studied," says Zimmerman. One study showed double the risk in children whose mothers suffered from psoriasis during pregnancy.
Zimmerman has also found an association with a mother's low levels of serotonin, a brain chemical known as a mood regulator and closely linked to depression. His study showed the mothers of autistic children having low levels of serotonin in the fluid that carries the chemical to the fetus, even though the women were not depressed. "A mother's levels are important to fetal brain growth," he says. "Mom's serotonin might be important to jump-start the fetus's production of its own."
Some scientists suspect that a mother's age could also be a risk factor. "We don't see teenage mothers or women in their early 20s bringing young autistic children to the clinic," says Zimmerman. "It's mostly mothers in their 30s and 40s." Advanced maternal age means more exposure to all kinds of toxins, viruses and chemicals, he adds, "and the older they are, the more likely people are to develop autoimmune diseases; this is especially true for women."