A study of twins finds that shared environmental factors influence the risk of autism more than previously thought and challenges previous findings about the significance of genetics.
Among identical and fraternal twins in whom at least one child has autism or autism spectrum disorder (ASD), shared environmental factors have a more substantial impact regarding development of the condition than do genetics, according to a study in the July 4 online Archives of General Psychiatry.
“A large proportion of the variance in liability can be explained by shared environmental factors (55% for autism and 58% for ASD) in addition to moderate genetic heritability (37% for autism and 38% for ASD),” reported Joachim Hallmayer, MD, Associate Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine in Palo Alto, California, and colleagues. “Our study provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated.”
A Shift in the Environment Versus Genetics Debate?
The study included data from monozygotic twin pairs (45 male, nine female) and dizygotic twin pairs (45 male, 13 female, and 80 sex-discordant) who were born between 1987 and 2004. The monozygotic twins were slightly older and had shorter gestation periods. The mothers of the dizygotic twins were also older than the mothers of the monozygotic twins, “consistent with the known increase in dizygotic twinning with maternal age, and more likely to be white and non-Hispanic,” noted the investigators.
For twins with strict autism, the researchers found that the probandwise concordance for male twins was 0.58 for 40 monozygotic pairs and 0.21 for 31 dizygotic pairs; for female twins, concordance was 0.60 for seven monozygotic twin pairs and 0.27 for 10 dizygotic pairs. For children with ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs and 0.31 for 45 dizygotic pairs; for female twins, concordance was 0.50 for nine monozygotic pairs and 0.36 for 13 dizygotic pairs.
“Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes,” Dr. Hallmayer and colleagues wrote. “The finding of significant influence of the shared environment, experiences that are common to both twin individuals, may be important for future research paradigms.”
Increasing evidence has shown that overt symptoms of autism emerge toward the end of the first year of life, the authors noted. “Because the prenatal environment and early postnatal environment are shared between twin individuals, we hypothesize that at least some of the environmental factors impacting susceptibility to autism exert their effect during this critical period of life,” Dr. Hallmayer’s group commented. “Nongenetic risk factors that may index environmental influences included parental age, low birth weight, multiple births, and maternal infections during pregnancy. Future studies that seek to elucidate such factors and their role in enhancing or suppressing genetic susceptibility are likely to enhance our understanding of autism.”
A Disorder of Fetal Programming?
In an accompanying editorial, Peter Szatmari, MD, of the Offord Centre for Child Studies, McMaster University in Hamilton, Ontario, Canada, stated, “Perhaps ASD can be considered, at least in part, a disorder of fetal programming. There is in fact evidence that certain risk factors that affect the maternal fetal environment may place the fetus at increased risk for ASD. Clearly a renewed effort needs to be undertaken through the use of well-designed community-based epidemiologic studies.
“Whatever happens in the future, the finding by Hallmayer and colleagues is an extraordinarily important one and has the potential to shift autism research into a new field of study in much the same way that the original twin study by Folstein and Rutter accomplished back in 1977,” Dr. Szatmari concluded.
—Colby Stong
A Link Between Maternal Antidepressant Use and Autism Risk in Offspring?
Exposure to selective serotonin reuptake inhibitors (SSRIs) among pregnant women, especially during the first trimester, may modestly increase the risk of autism spectrum disorder (ASD) in their children, according to a study in the July 4 online Archives of General Psychiatry.
The findings were based on 298 children with ASD and 1,507 randomly selected control children and their mothers enrolled in the Kaiser Permanente Medical Care Program in Northern California. Data regarding prenatal exposure to antidepressants were available for 20 children and 50 controls. After adjusted logistic regression, the researchers found a twofold increased risk of ASD associated with SSRI treatment in mothers in the year before delivery (adjusted odds ratio, 2.2). The strongest effect was linked with treatment during the first trimester (adjusted odds ratio, 3.8). No increased risk was observed among mothers with a history of mental health treatment in the absence of prenatal exposure to SSRIs.
“The fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” stated Lisa A. Croen, PhD, of the Division of Research, Kaiser Permanente Northern California in Oakland, and colleagues. “Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or fetus of untreated mental health disorders.”
“Perhaps it is a coincidence that the odds ratio for ASD risk in the study by Croen and colleagues increases when first-trimester exposure to SSRIs is the sole factor,” stated Pat Levitt, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, in a related commentary. “However, it is exactly that time of human brain development during which cortical and subcortical neuronal populations are being produced, migrating to their final destinations and beginning the long process of wiring. While much occurs later, the establishment of a strong foundation developmentally may be an essential component of healthy brain development.”