Risk factors in autism: A deeper look at the subtype argument

It has been well demonstrated that prenatal (during gestation) and perinatal (after birth) risk factors are associated with autism spectrum disorders. But which risk factors have a significant relationship with the prevalence of autism remains up for debate. Several papers argue that maternal stress during pregnancy is an important risk factor for autism, but even this proposition is muddled, as several prenatal stressors do seem to be related to autism (e.g., the experience of a natural disaster, loss of a loved one), whereas others, albeit surprisingly, do not (e.g., physical abuse).

An answer to these discrepant findings may lie an argument supported by many autism researchers: that autism is a conglomeration of several distinct subtypes, each with their own genetic and behavioral profile. If there exist specific subtypes of autism, is it possible that one risk factor may contribute to one subtype while not influencing the occurrence of another?

A recent paper published in the Journal of Autism and Developmental Disorders asks this very question. Janne Visser and colleagues from Radboud Unversity in The Netherlands argue that defining autism broadly versus narrowly affects which risk factors seem to have a significant impact. In their study, research participants underwent an extensive diagnostic protocol, including the standard diagnostic measures for autism (ADI-R and ADOS) as well as several other diagnostic tools. Following the diagnostic protocol, participants were classified as either having autistic disorder (AD), a narrowly defined diagnosis, or pervasive developmental disorder-not otherwise specified (PDD-NOS), a more broad diagnosis. Parents of these children and those of matched controls completed a survey with questions pertaining to many pre- and perinatal risk factors.

The most robust finding in this study was an expected one. When the AD and PDD-NOS groups were combined into one autism spectrum disorder group, this group demonstrated an increased occurrence of several risk factors, including maternal infections, prenatal stress, and low birth weight, as compared to the control group. The occurrence of these risk factors was also related to the severity of core autism symptoms, such as repetitive behaviors and impairments in communication.

Interestingly, however, when the AD and PDD-NOS groups were compared to each other, one risk factor, smoking during pregnancy, stood out as being significantly related to PDD-NOS, but not AD. Smoking during pregnancy was also related to lower IQ, but only in the PDD-NOS group, a finding that remained even after controlling for birth weight, which is commonly affected by smoking. This distinction between two autism subtypes provides support for the argument that subtypes of autism (narrowly versus broadly defined) may have different environmental and genetic influences.

Smoking during pregnancy is also a risk factor associated with ADHD, suggesting that this disorder may have underlying mechanisms similar to those of PDD-NOS, but not of AD. These mechanisms may be more than environmental, as Visser and colleagues propose. Smoking during pregnancy may be associated with specific genetic traits that can be passed from mother to child. These traits may contribute to the development of disorders, such as PDD-NOS and ADHD.

Why smoking during pregnancy wasn’t related to AD remains to be seen. It’s clear, however, that future studies should examine risk factors as they relate to not just autism in general but to specific subtypes of this disorder. Fortunately, the subtypes argument is being supported increasingly in the field of autism research. Although it begs more questions about each subtype and its associated characteristics, the subtypes argument provides a more focused and realistic approach to studying the true spectrum that is autism.