ReviewPrenatal stress and risk for autism
Section snippets
The symptoms, prevalence, and costs of autism
Autistic disorder (AD) is a particularly severe neurodevelopmental disorder, with great costs for society as well as for patients and their families. The most widely used diagnostic criteria for AD are those described in the revised text edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) of the American Psychiatric Association (APA, 2000). Briefly stated, those criteria involve (a) qualitative impairment of reciprocal social interactions, (b) marked impairment in
Overview of genetic and environmental factors in autism
Although the importance of genetic factors in AD is strongly suggested by data from twin, family, and genetic association studies (e.g., Campbell et al., 2006, Folstein and Piven, 1991, Muhle et al., 2004), the same studies also indicate that environmental factors play a significant role. The much higher concordance rates in monozygotic (MZ) compared to dizygotic (DZ) twin pairs do point to a high heritability in AD, but these rates also suggest that exposure to environmental modifiers may
The importance of identifying preventable environmental causes of autism
Because AD is so devastating and there is, with rare exception, no established method for preventing AD, research is urgently needed to identify potential environmental factors that contribute to AD. Identification of environmental factors that can be avoided, prevented, or ameliorated by programs of primary prevention is therefore especially important.
In this paper, we review several complementary lines of research that suggest that one environmental factor that increases risk for AD is
Prenatal stress and increased risk of AD
Two retrospective studies have found that prenatal exposure to stressful events is associated with increased risk of AD. Ward (1990) compared data from prenatal records of 59 mothers of AD children to records of a matched sample of 59 mothers of healthy children. He found that the mothers of AD children reported having experienced significantly more family discord during the pregnancies with the AD children: 19 of the mothers of AD children, but only 2 of the control mothers, experienced
Research on related effects of prenatal stress
The existing evidence for significant effects of prenatal stress on postnatal behavior is robust. There are more than 100 experiments published in the scientific literature on the effects of prenatal stress in laboratory animals. There are also several dozen studies of humans, including several involving natural experiments. While an exhaustive review of all these studies is beyond the scope of this paper, several important and well-established general principles that are particularly pertinent
Postnatal hypersensitivity to stress: a marked effect of prenatal stress
While prenatal stress can produce a wide range of behavioral, endocrinological, and anatomical outcomes, it tends to have particularly strong effects on the systems that mediate the organism's response to stress.
Prenatal stress can produce other abnormalities commonly found in AD
In addition to contributing to behaviors that resemble essential symptoms of AD, prenatal stress is also associated with an increased risk of developing other conditions that tend to be associated with AD, such as abnormalities in cognitive, neurological, and immune functions.
Mechanisms by which prenatal stress can disrupt fetal brain development
Experiments with laboratory animals indicate that prenatal stress can disrupt brain development through several mechanisms (Mulder et al., 2002). The neuroinflammatory effects just noted represent one mechanism. Prenatal stress can also (a) reduce uterine and placental circulation, inducing fetal hypoxia; (b) stimulate the release of maternal stress hormones that can cross the placenta and alter the development of the HPA axis; (c) produce complications of pregnancy and delivery; and (d) have
Can prenatal stress help explain other risk factors for AD?
Converging lines of evidence suggest that prenatal stress might be a common factor that helps to mediate the association of AD with several of its previously identified risk factors.
Factors that may moderate the effect of prenatal stress on risk for AD
Several factors are likely to moderate how prenatal exposure to stressful events affects prenatal development and the risk for AD. One such moderating factor is likely to be the genetic susceptibility of mother and fetus. In animals, there are well-established genetic strain differences that influence the behavioral and endocrine responses of individuals to stress.
Recent research has found evidence for interactions between genes and the postnatal environment in the etiology and pathogenesis of
Implications for prevention and treatment
If pre- and peri-natal exposure to stressful events is shown to be a significant risk factor for AD, this could have a number of important clinical implications for prevention and treatment.
Directions for future research
Studies to date on prenatal stress and AD, while yielding significant evidence for an association, nonetheless had key limitations. New research is needed to address these limitations. For example, high levels of stressful events reported by mothers during their pregnancies with AD children (Ward, 1990, Beversdorf et al., 2005) could have been due to biased retrospective reports by mothers. To control for this possibility, one approach would be to ask mothers about life events that occurred
Conclusion
In summary, empirical evidence from a wide variety of studies strongly suggests that prenatal stress may play a significant role in the etiology of AD. This evidence comes from studies involving many different investigators, research designs, and subjects, including humans and different animal species. This research indicates that prenatal stress can cause a variety of postnatal abnormalities, including not only the behaviors that resemble the defining core symptoms of AD, but also other
Acknowledgements
This paper was supported in part by grants from the Autism Speaks/Cure Autism Now Foundation, NIMH (MH 071286) and FIC (D43 TW05807), and the Stanley Medical Research Foundation. The authors thank Beverly Gilligan, Siena Napoleon, Catherine Riffin, Andrea Surova, and Bruno Trinidade for their help with library research and the typing of the manuscript.
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