To expand on the recent twins study, Hallmayer said, the next step should include siblings, so as to collect information on the entire family.
“We need to see how the sibling rate for autism or ASD rate compares with the dizygotic rate,” he said.
“The risk of siblings being affected by ASD is higher than we previously thought,” Hallmayer said. “We may be talking about some other forms of autism that we have overlooked before.”
The recently published Baby Siblings Research Consortium study, which used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD, found that 18.7% of the infants developed ASD.2
Discussing the relevance of the twins and sibling studies for psychiatrists, Hallmayer said the twins study demonstrated that autism is as etiologically complex as schizophrenia, bipolar disorder, and major depression. Regarding the sibling research, he recommended that psychiatrists refer parents of a child with autism or ASD who are contemplating another pregnancy to very good genetics counselors “so they know what the risks are.”
Evidence is accumulating that overt symptoms of autism emerge around the end of the first year of life. Because prenatal and early postnatal environments are shared between twins, the twin study investigators hypothesized that shared environmental factors might include parental age, low birth weight, multiple births, and maternal infections during pregnancy.
On the basis of the twins and baby siblings studies, Hallmayer speculated that the shared environmental factors, such as autoimmune factors in the mother, might be ones that affect the development of the child in the womb.
One of Hallmayer’s coauthors on the twin pairs with autism study was Lisa Croen, PhD, Senior Research Scientist with Kaiser Permanente Northern California and Director of the Kaiser Permanente Autism Research Program. Recently, she was first author on a study that examined whether exposure to antidepressants in early pregnancy may increase the risk of ASD.3
The population-based study involved 298 children with ASD and their mothers and 1507 randomly selected control children and their mothers drawn from the Kaiser Permanente Medical Care Program in Northern California.
“We found an approximately 2-fold increased risk of ASD associated with treatment with SSRIs of the mother during the year before delivery and an approximately 3-fold increased risk associated with treatment during the first trimester, independent of indication,” the investigators reported. “Additionally, we observed no increase in ASD risk associated with a history of mental disorders after controlling for SSRI use during pregnancy.”
“This is the first study to ever establish this association, and it has to be treated with a great deal of caution,” Croen said. “It has to be replicated before we can say there is a causal connection. And we know there is a risk to the mother of not being treated for depression if she’s depressed, so the risk to the baby really has to be balanced with the potential risks of not treating the mom for depression. . . . We are not advocating that women stop taking their medication during pregnancy. It is really a decision that has to be made between the patient and the provider as to what’s best.”
1. Hallmayer J, Cleveland S, Torres A, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011;68:1095-1102.
2. Ozonoff S, Young GS, Carter A, et al. Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics. 2011 Aug 15; [Epub ahead of print].
3. Croen LA, Grether JK, Yoshida CK, et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011;68:1104-1112.
4. Croen LA, Connors SL, Matevia M, et al. Prenatal exposure to β2-adrenergic receptor agonists and risk of autism spectrum disorders. J Neurodev Disord. 2011;3:307-315.
5. Croen LA, Grether JK, Yoshida CK, et al. Maternal autoimmune diseases, asthma and allergies, and childhood autism spectrum disorders: a case-control study. Arch Pediatr Adolesc Med. 2005;159:151-157.
6. Croen LA, Goines P, Braunschweig D, et al. Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study. Autism Res. 2008;1:130-137.
7. Goines PE, Croen LA, Braunschweig D, et al. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: a case-control study. Mol Autism. 2011;2:13.