A Copyright Harvard Health Publications
Several studies raise questions about cause and prevention.
The conventional wisdom has always been that autism spectrum disorders (ASD) develops mostly because of genetic rather than environmental factors. Indeed, ASD is usually considered among the most heritable psychiatric disorders, with studies in twins suggesting that genetic factors account for at least 90% of the risk of developing an ASD, much more than the genetic risk of depression, anxiety, or other psychiatric conditions.
A large population study in twins turned the accepted wisdom on its head by suggesting that environmental factors may be more important in the development of ASDs than previously realized. Several other studies identified possible environmental culprits: the use of selective serotonin reuptake inhibitors (SSRIs) or lack of folic acid early in pregnancy, and a variety of complications near or shortly after giving birth. It’s clear that genetic risk still matters, but leading researchers are rethinking what causes ASDs and how to prevent them.
The research is a reminder of just how complex autism spectrum disorder is. Altogether, it’s likely that several genetic vulnerabilities are interacting with multiple environmental factors simultaneously.
The key deficits in autism spectrum disorder (ASD), as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) , are problems with communication and social interaction as well as behaviors, interests and activities that are restricted and repetitive. Examples are ritualistic behaviors like constantly tapping of fingers or humming.
The conventional wisdom that ASD is largely genetic goes back to the 1970s, when studies found that if one identical twin developed an ASD, there was a 90% chance that the other twin (who shared the same genes) would do so as well. In fraternal twins, who like other siblings share only some genes, the concordance rate (the likelihood that both would develop ASD) was as low as zero
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changed the way these disorders are classified. Autism spectrum disorder (ASD) is the term now designated for disorders that had been classified separately in the prior edition of the DSM. ASD now incorporates autistic disorder (autism), Asperger’s disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified.
For years, critics pointed out that the concordance rate in fraternal twins seemed too low to be credible, which would throw off the heritability estimate. Meanwhile, another line of research, on ASD prevalence, also raised concerns.
In the 1960s, researchers estimated that four to five children out of 10,000 would develop an ASD. Prevalence of ASDs may now be more than 100 per 10,000 children. Genetic changes, which take thousands of years to develop, certainly do not explain this increase. Certainly, some of the change is due to improved awareness and readiness to diagnose ASD. Yet, one or more recent environmental factors might be also be involved.
In more recent studies of heritability, the concordance rates for ASD in identical twins have been lower than previously thought. In a large study using up-to-date diagnostic criteria (the California Autism Twins Study, led by a team at Stanford), ASD concordance rates for identical twins ranged from 50% for girls to 77% for boys. At the same time, they found concordance rates of 31% to 36% for same-sex fraternal twins, more than previously estimated. The researchers further estimated that genes accounted for about 38% of the risk of developing an ASD, while environmental factors that twins shared, such as events during pregnancy, accounted for 58%. These results implied that environmental factors play much more influential a role than previously suspected.
It’s important to point out that environment is an all-encompassing term in research papers. Although lay readers often interpret the term as something in the atmosphere, such as toxins, scientists use it to describe anything outside the body. In ASD research, the environmental factors being investigated include prenatal conditions in the womb and complications at birth.
SSRIs and pregnancy
A number of studies have looked at the possibility that children of mothers who took a selective serotonin reuptake inhibitor (SSRI) during pregnancy are at higher risk for developing ASD. This question is of great importance because depression is fairly common and SSRIs are the most widely prescribed antidepressants.
A case control study done in California found that there was a small but significant association between SSRI treatment and ASD cases. A similar finding emerged from a later study done in Quebec, Canada.
These data are difficult to interpret, because psychiatric illness in the mother during pregnancy is also associated with ASD in children. It is therefore not possible to know whether ASD is connected to the disease, its treatment, or some other factor.
The findings about SSRIs need to be interpreted with caution until more is known. It should also be recognized that it is not safe to leave depression untreated, and not just for the sake of the mother. Untreated depression can also cause problems in the offspring.
Vitamins and folic acid
Folic acid (one of the B vitamins) plays a critical role in the development of the brain and nervous system. Investigators have seen this, for example, in the connection between folate deficiency and deformities of the spinal cord such as spina bifida. Research has also suggested that women who take multivitamins several months before conceiving and during the first month of pregnancy may significantly reduce their risk of giving birth to children with ASDs. As a result, it has been recommended that women of child bearing age should be taking daily Folate, with the recommended dose being 400 micrograms per day.
Women may need to be cautioned, however, not to take too much folate, because another study has raised the question that levels of folate that are too high may be associated with an increase in the incidence of ASD.
Advice, with caveats
Complications during birth or soon afterward (the perinatal period) can also affect risk of developing ASDs. A careful review of multiple studies identified multiple perinatal risk factors for ASDs. Among those that increased risk the most were anemia (an iron deficiency) in the newborn, inhaling meconium (fetal feces), birth injury or trauma, and a mother who hemorrhaged during birth. Some of these complications can be prevented by good prenatal care, but others may be an early sign of developmental abnormalities.
And while the research has renewed focus on environmental factors that might influence ASD risk, genes still matter as well. The consensus has always been that ASDs develop because of alterations in multiple genes; the studies are identifying multiple environmental factors that also contribute, probably by interacting with genes.
Until more is known, the best advice for women is to discuss their own particular circumstances with their doctor. Here are some basic principles to consider with regard to the risk of giving birth to a child with an ASD:
- Take a multivitamin. Taking 400 micrograms of folic acid daily appears to help prevent birth defects such as spina bifida. It’s not yet clear whether this will also help reduce risk of ASDs, but it may be an added benefit of taking a daily dose of folate. Women should discuss the dosing with their doctors, since taking too much folate may present risks.
- Ask about SSRIs. Women who are taking an SSRI (or who develop depression during pregnancy) should talk with a clinician about all the risks and benefits of these drugs. The key is to balance the risks of taking a medication against the risks of leaving depression untreated.
- Practice prenatal care. Eating nutritious food, trying to avoid infections, and seeing a clinician for regular check-ups can increase the chances of giving birth to a healthy child.