In the last few decades, an increasing number of children are being diagnosed with Autism Spectrum Disorders, fueling both speculation and research about the causes. Some wonder whether the increase is “real,” or whether ASD has been present at the same rates, but is being correctly diagnosed more often. A few studies have attempted to examine artifacts such as improved diagnosis, early-age detection and changes in diagnostic criteria used by physicians and psychologists. This research, much of it conducted using data from the California Department of Developmental Services, demonstrates that although a portion of the rise may be attributed to these factors, about half of the increase remains unexplained. Ultimately, the proportion explained by changes in root causes versus how it is diagnosed may remain elusive. Nevertheless, a few conclusions are clear.
First, there is no single cause of ASD, and few if any cases of ASD results from one factor acting alone. Second, both genes and environment play substantial roles. Most genes probably increase susceptibility. Here, environment may act in concert with the underlying susceptibility or may contribute to it, by altering which genes are expressed (i.e., turned “on”). It should be underscored that environment is broad. It includes diet and nutrition; bacteria, viruses, medical procedures and medications; and environmental chemicals (naturally occurring and man-made) in air, food, water, soil and everyday household and personal care products used for cleaning homes or on our bodies or hair. In short, environment covers anything not inherited in our DNA code. Third, to understand root causes of this condition, we need to explore causes of both ‘background' rates of ASD (genes, or exposures present for a long time) and the surge in cases (primarily exposures that have changed in recent decades).
Emerging evidence suggests some promising clues.
1) Nutritional status of the mother at the start of her pregnancy. Two studies examined intake of prenatal vitamin supplements in the few months just before conception and very early pregnancy. Both showed about 40 percent lower risk in children whose mothers took these supplements. Notably, regular multivitamins, containing less folic acid, made no difference. Particularly intriguing was that the strongest ‘protection' from vitamin supplementation was when the woman or child was genetically predisposed to poorer absorption or metabolism of folic acid. Prenatal vitamin supplements are currently recommended to prevent neural tube defects, rare malformations in which the brain fails to form properly. It appears that ASD may be a second reason for taking these supplements, preferably before pregnancy.
2) Certain classes of insecticides. These products are widely used in agriculture, homes and gardens. Elevated risk for autism was found in children whose mothers lived near agricultural applications of any of three different chemical insecticides: organochlorine, organophosphate and pyrethroid. Concern about safety arises because these compounds are designed to be harmful – usually lethal – to insects, yet the mechanisms for inducing toxicity are relevant to mammals, including pets and humans. While typical human exposures may have little impact on an adult, the developing fetus and infant may be especially vulnerable. First, barriers that protect the brain later in life are not fully developed; second, embryonic cells must differentiate into specialized cells (e.g., neurons, muscles, glands) that perform specific functions and must migrate to their proper locations through complex processes requiring chemical signals to turn genes on and off at exactly the right times.
3) Air pollution from traffic or industrial sources. Using residential addresses, researchers found that children with ASD, as compared to those with typical development, on average resided closer to freeways or to higher levels of outdoor air pollutants. The specific pollutants varied across studies, with the most consistent results for small particles and several metals.
4) Some viral infections and/or fever. Many decades ago, children congenitally exposed during an epidemic of rubella were far more likely to develop autistic symptoms. Today, vaccinations have generally eliminated this disease. On the other hand, influenza, particularly when accompanied by a fever, or fever from any cause, has been reported more commonly in pregnant mothers whose children developed autism than by those whose children developed typically. These microbes may act on the developing central nervous system (CNS) or they may produce an inflammatory reaction in the mother, which then acts upon the fetal CNS. Indeed, poor regulation of immune responses may contribute to ASD.
The verdict is not in yet, and despite efforts of researchers to ensure valid results with no interference from factors not studied, research on complex disorders with multiple causes is challenging. Besides the exposures described above, newborn conditions such as low APGAR scores, preterm delivery or fetal distress may indicate higher risk for autism. Also, parents of children with ASD are, on average, older than parents of those who develop typically, and age can be a marker for poorer quality gametes, chronic or auto-immune conditions, more interventions and diagnostic procedures during the pregnancy, and accumulated chemical exposures or the damage they produce. Moreover, chromosomal anomalies, gene mutations and deleted or duplicated sections of DNA are more frequently found in the genome of persons with ASD, but are not always inherited from parents. These de novo genetic events may be due to unidentified environmental insults right around or shortly after conception.
A decade ago, only a handful of scientific reports dealt with root causes of autism that might be modifiable, either by individual behaviors or at the wider population level. Today, this research is burgeoning and there is hope that strategies to actually prevent ASD or reduce its severity are on the horizon.
Irva Hertz-Picciotto is a professor at the UC Davis MIND Institute.