Despite a flurry of research on autism spectrum disorder, the syndrome remains mysterious to most Americans. But experts say the answers are starting to come into focus.
Autism was once considered the “kiss of parenting death,” as Dr. Lawrence Diller, an expert in childhood developmental disorders and author of the influential book Remembering Ritalin, put it.
Before autism came to be seen as a spectrum of disorders ranging in severity, a diagnosis meant “that the parent would have no relationship with their child,” Diller said.
Those affected by autism have difficulties communicating and interacting with others.
With milder cases diagnosed as part of autism spectrum disorder (ASD), autism isn’t a parenting death sentence anymore. But with rates of the developmental disorder doubling over the past decade, would-be parents still dread it. Researchers have hustled to provide some answers.
The discoveries they’ve made can, for the nonscientist, seem to increase rather than whittle away at the mystery of autism.
It’s due in part to the many unanswered questions about this disorder that debunked research blaming vaccines for autism has continued to sway some parents.
One scientific certainty, reached after reviewing decades of studies on the effects of routine childhood vaccinations, is that the measles, mumps, and rubella, or MMR, vaccine is
“Autism is a pervasive disorder that poses incredibly difficult challenges and burdens on the families who are affected. Everybody is looking for answers — scientists, educators, and, most of all, families,” said Dr. Paul Wang, head of medical research at the advocacy organization Autism Speaks.
The biggest question about autism is why the diagnosis rate is increasing so quickly.
It has more than doubled since 2001, now affecting one in 42 boys and one in 189 girls.
Broader diagnostic criteria account for some of that growth, experts say, but not all. In fact, ASD is still probably underdiagnosed in less affluent communities, experts said.
A recent analysis found that changing diagnostic and reporting criteria account for 60 percent of the increase in autism rates. In other words, the disorder may not be increasing quite as fast as the numbers indicate, but it is still on the rise.
“We believe that there is a very real increase in autism cases that cannot be fully attributed to changes in diagnosis and awareness,” Wang said.
Autism has a genetic component, but genes alone can’t account for the increasing prevalence of the disorder. And how exactly autism risk works remains unclear, at least for the layperson.
In about 1 in 3 sets of identical twins, one twin develops autism and the other does not. A recent study found that even in siblings who both have autism, the genetic fingerprints of the disease are not the same.
There must be an environmental component as well, researchers agree — but what is it?
The list of environmental factors that may contribute to autism is wildly diverse, including air pollution, older fathers, diabetic mothers, viral infections during pregnancy and emotional trauma in the mother’s life long before she became pregnant.
What picture of autism can we draw from these seemingly unrelated findings?
Experts agree that, although the outward signs of autism show up in toddlers just as they are getting a major course of vaccines, the condition is most likely set by the time a child is born.
“The evidence so far is strongest for factors that affect the baby even before birth. That is, the processes underlying autism start very early in life, well before the first birthday, and even during pregnancy,” Wang said.
Dr. Daniel Geschwind, director of the Center for Autism Research and Treatment at the University of California, Los Angeles, focuses on the genetics of autism.
The genes linked to autism “affect the early, early development of brain circuits such as the kind of neurons, the kind of cells that are born and how they’re connected to each other,” he said.
Much of the strongest evidence on which environmental factors can spur autism also focuses on what happens to a fetus in the womb, according to Andrea Roberts, Ph.D., a researcher at the Harvard School of Public Health.
For instance, air pollution is thought to be a possible trigger for autism, but it’s the pregnant mother’s exposure that is most likely the problem, not the baby’s in its first years of life.
One trying to pin down the genetics of autism could reasonably throw up their hands at headlines like “27 Genes Newly Linked to Autism” and “Not Even Siblings with Autism Share the Same Genetic Risk Factors.”
The finding that siblings don’t share the same genetic blueprint for autism surprised even the experts, Wang said. Even so, the genetics of autism are about as well understood as they are for any other complex behavioral trait.
“It’s not like tuberculosis. It’s not a disease, it’s a syndrome. Just like having a fever is not having a disease — there are many different causes of fever,” Geschwind said.
Another comparison is often drawn with Alzheimer’s disease. Few doubt that a risk for Alzheimer’s is passed down through families. But a large number of genes, together, create the risk.
“The genetic landscape of any complex common disease like Alzheimer’s disease, Parkinson’s, or autism is going to be complex. There are different forms, and there’s not one single genetic cause,” Geschwind said.
Through screening the genomes of those affected by autism and their families, research has produced a complicated picture of ASD’s genetic underpinnings, but there are some basic themes emerging.
The list of genes linked to autism stands at about 100, according to Geschwind, but he wouldn’t be surprised to see it reach 500 in time.
Some of ASD’s genetic footprints are fairly straightforward.
Fragile X syndrome, a set of developmental problems that often includes autism, is caused by single clear genetic problem involving the X chromosome. Boys with Fragile X are more likely to be on the autism spectrum than girls — and this points to one of the clearest findings in genetic research.
Girls seem to have something protective in their genetics that makes them less likely to develop autism. Genetic risk factors have to be stronger in girls for them to develop autism spectrum disorder. When the genetic risks are strong enough to produce autism in girls, the result tends to be more severe cases.
In some cases, children with autism spectrum disorder simply inherit risk factors from both parents. Each parent’s genes may not be strong enough to produce a diagnosable disorder, but when combined, the result is a child with ASD.
“Most of the genetic risk for autism comes from many, many very common genetic variants. We can’t think of it as being caused by any one gene; it’s caused by a lot of different genes. One person might have variants on this set of genes, the other has variants on another, and one of the kids might get both sets,” Roberts said.
For instance, in one influential study, a mother who did not have autism nevertheless had a history of social isolation and repetitive behaviors. She had a GRIP1 mutation. She had two sons who were diagnosed with ASD. One, with a milder case, also had one copy of the mutation. The brother with the more crippling disorder had two copies.
One theory for the rise of autism that several experts mentioned in interviews with Healthline is that adults who have some genetically driven social impairments may be more likely to have children now than they would have been in the past. Because those who struggle to communicate with people often excel at communicating with computers, the rise of high-tech professions has given people with ASD more chances to succeed and to meet potential mates.
“Even though it’s a genetic thing, you can have some changes in prevalence and frequency,” said Wang.
Many of the genes linked to autism are de novo mutations, or genetic mutations that happen during fetal development. In these cases, the disorder is genetic but not inherited.
The tendency for parents to have children later may partially account for increases in genetic disease. Older mothers were first linked to a greater chance of ASD in children. But older fathers play a role, too.
As men age, the sperm they produce is more prone to creating de novo genetic mutations in their offspring. A 2012
There’s a variety of genes affected and multiple ways in which they’re mutated, but many of the genetic trouble spots are linked to early brain development, Geschwind said. Recent studies have suggested that some of the same genetic patterns can result in schizophrenia instead of autism, a mental illness that also affects social interaction.
In fact, one strange new finding about autism that seems to point to an environmental driver may instead be evidence that genetic risk for ASD is bundled with the risk for post-traumatic stress disorder, or PTSD.
In a 2013 study, Roberts found that women who were seriously abused as children were likelier to have children with autism. Childhood abuse is also likely to cause PTSD, Roberts said.
One way to interpret the correlation is to say that the abuse changed the way the women’s bodies dealt with stress, which, in turn, interrupted some normal process of fetal development.
“Stressful experiences in childhood affect your biology throughout life,” Roberts said.
But Roberts sees the study as an indication that the women themselves were genetically predisposed to PTSD, and those same genes were among those that led to autism in their offspring.
“My interpretation of that paper is that it’s probably showing genetic overlap,” she said. “These mental illnesses are all associated with different kinds of biological dysregulation, particularly inflammation, and hormonal response in the stress response system.”
Genetics only create the risk of autism. It’s environment that turns a genetic risk into an actual problem. So what is the environmental catalyst?
There’s no clear answer, but there is a short list of theories that have a growing and credible body of evidence to back them up.
The first is maternal nutrition.
“Nutrition is very, very important, maybe even starting before pregnancy,” said Wang.
Folic acid is now commonly prescribed to expectant moms to ward off birth defects. It may also help reduce the risk of autism. Interestingly, folic acid may steer developing infants with certain genetic risk profiles safely away from actual autism, while having no effect on those with distinct genetic risks.
After having a child, a mother’s store of folic acid falls without a supplement. That may provide a simple explanation for another strange finding on autism: A study published in the journal Pediatrics in 2011 found that children conceived within a year after the birth of an older sibling were more likely to develop autism. The authors thought the most likely reason was “maternal nutritional depletion” of folic acid, iron, or polyunsaturated fatty acids.
Stress could also be a reason, the study noted. A mother’s stress could interfere with normal developmental processes that lead to a healthy newborn
Some researchers also suspect that skyrocketing rates of obesity may be partly to blame for the uptick in ASD.
Studies have linked diabetes, obesity, and hypertension in the mother to higher rates of autism in their children. Mothers whose metabolic processes are abnormal may also risk creating an unhealthy developmental environment for a fetus.
“There are biologically plausible mechanisms by which that could happen, and weight is certainly something that’s changed a lot,” Roberts said. “We know that moms who are overweight have a much higher risk of a variety of adverse birth outcomes.”
Several studies, including one done by Roberts, also link exposure to air pollution during pregnancy to higher rates of autism. The most common culprit is particulate matter, the tiny particles whose biggest source is the burning of diesel fuel. Particulate matter, which creates chronic inflammation in the body when inhaled, has been blamed for other poor health outcomes in adults.
Wang also pointed to recent findings from a Swedish study that women who were hospitalized for bacterial infections during pregnancy were 30 percent more likely to have an autistic child. Here, it’s probably the mother’s immune response that interferes with normal development.
“Infections and inflammation during pregnancy, and exposure to air pollutants during pregnancy, are two groups of factors for which the evidence is strong,” Wang said.
While most of the evidence on environmental triggers of ASD is based on correlation, there are some animal studies that show that immune response in the mother during pregnancy can trigger neurodevelopmental disorders.
These general findings don’t satisfy researchers or parents. But Autism Speaks reminds parents that the risk factors most likely only play a part when the fetus already has genetic risk factors.
“In the presence of a genetic predisposition to autism, a number of nongenetic, or ‘environmental,’ stresses appear to further increase a child’s risk … It is important to keep in mind that these factors, by themselves, do not cause autism. Rather, in combination with genetic risk factors, they appear to modestly increase risk,” the organization says on its website.
Parents aren’t likely to stop worrying about autism any time soon. But as they wait for science to give more complete answers about this mysterious disorder, prospective parents can at least play a more active part in managing the risks.