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Programmed for Psychopathology?
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Programmed for psychopathology?
Stress during pregnancy may increase children's risk for mental illness, researchers say.

Sadie F. Dingfelder

Add one more apparent risk factor for mental illness to the already lengthy list: In addition to the often-studied effects of genetics and upbringing, some researchers suggest that maternal environment, the hormone-laced bath that envelops a developing embryo, may contribute to the later development of psychopathology. 

In particular, stress and its effects on pregnant mothers' hormonal balance appear negatively related to the mental health of their children, according to a literature review published in the January Psychological Bulletin (Vol. 130, No. 1). Schizophrenia, depression and behavioral difficulties are just a few mental health problems that children may be at increased risk for when they have stressed mothers.

Researchers at the Utrecht University Medical Center in the Netherlands reviewed 255 human and animal subject studies on the effects of maternal environment and found no single pathway responsible for increased levels of psychopathology in humans and behavioral abnormalities in animals with mothers exposed to environmental stress--from work-related stress in humans to the stress of tail-shocks in rodents. 

"Exposure to maternal stress may be related to abnormalities in brain development," says primary investigator Anja Huizink, PhD, of Utrecht University and Erasmus Medical Center. These changes may broadly affect the later functioning of infants, says Huizink, who contends that maternal stress does not engender vulnerability to any one mental illness, a theory held by some researchers of maternal stress. 

Early theories

Unlike Huizink, some scientists have found support for the theory that prenatal stress increases vulnerability to a particular psychopathological outcome: schizophrenia.

One study conducted in 1998 by professor Jim van Os, MD, PhD, of the Netherland's Maastricht University, investigated the connection between maternal stress caused by the German invasion of the Netherlands in May 1940 and the later psychopathology of babies born to mothers pregnant during that invasion.

Using information from the Netherlands National Psychiatric Case Register, a comprehensive record of psychiatric in-patient admissions, van Os and his colleagues tracked the mental health of more than 100,000 men and women born to mothers who were pregnant during the invasion. They found that these babies, compared with babies born in the prior or subsequent year, were more likely to later develop schizophrenia. The researchers found no significant vulnerability for affective disorders.

While stressed babies' increased incidence of schizophrenia was statistically significant, the effect was small. Overall, there was less than a 0.5 percent difference in the prevalence of the mental illness between the two groups--potentially due to the multiple genetic and environmental factors that contribute to mental illness. However, for babies exposed to stress during the first trimester, the effect proved to be more robust.

"Early effects, at least during the first or second trimester, affect the children most because that is when the development of the brain is in its most critical stages," says van Os. "You'd expect anything affecting brain development then would have long-lasting effects."

Stress begets fetal distress

While the general or specific vulnerability to mental illness continues to be a hot topic, most scientists agree that maternal stress affects infants through hormonal mechanisms.

One such mechanism, discovered through animal studies, involves the hypothalamic-pituitary-adrenal (HPA) axis. Chronic activation of this system in mothers, says Huizink, may be responsible for HPA dysregulation--their offspring's difficulty controlling stress hormones. HPA dysregulation has been associated with greater emotionality and difficulty calming down after a stressful situation, explains Huizink.

Though the placenta provides embryos with some protection against mothers' increased stress hormone levels, placental levels of the stress hormone cortisol vary in direct proportion to the mother's levels of the hormone, says Huizink. In animals, increased fetal exposure to these stress hormones leads to decreased numbers of stress-hormone receptors in the hippocampus, the part of the brain responsible for mediating stress response.

Decreased sensitivity in the hippocampus may account for difficulties regulating stress responses, which have been observed in mice and primates born to stressed mothers. In a 1990 study published in Physiology and Behavior (Vol. 48, No. 2), Aviva Wakshlak, PhD, and her colleagues at Hebrew University-Hadassah Medical School in Jerusalem, found that rats born to stressed dams experienced heightened emotionality and timidity. For example, they avoided open arms of mazes and tended to defecate excessively. 

In these mice, says Huizink, the stress-hormone regulatory system seems to be impaired, leading to difficulty stabilizing hormones and calming down after a danger has passed. A similar effect may be found in prenatally stressed humans, says Huizink.

"It is possible that these individuals are more sensitive to stress later in life," she says. And oversensitivity to stress, notes Huizink, is related to a variety of mental illnesses, including affective disorders.

Vivette Glover, PhD, who runs the Fetal and Neonatal Stress Research Group at the Imperial College of London, agrees. In a study of 7,144 mothers and babies from the Avon region of England, published in the December 2002 issue of the Journal of the American Academy of Child and Adolescent Psychology (Vol. 14, No. 12), Glover and her colleagues found that women who reported experiencing high levels of anxiety during pregnancy were twice as likely as nonstressed women to have children with behavioral difficulties, depression and anxiety, which the researchers measured when the children were 4 and 7 years old.

"We were able to focus on anxiety prenatally, and not later," says Glover, who also statistically accounted for the potential confounding effects of smoking, alcohol abuse, birth weight, maternal age and socioeconomic status--all factors that tend to correlate with maternal anxiety and may affect the developing baby directly.

However, says Huizink, while the findings of her research review converge on the idea that maternal anxiety adversely affects developing humans, precisely how this happens remains an open question. Additionally, she notes that researchers still do not know how intense maternal stress must be to adversely affect developing infants. 

"There are clues we can find in animal studies," she says, "but we don't know yet if the same mechanisms apply in humans."


* Caspi, A., Sugden, K., Moffitt, T., Taylor, A., Craig, I., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation in the 5-HTT gene. Science, 301, 386-389.

* Huizink, A., Mulder, E., & Buitelaar, J. (2004). Prenatal stress and risk for psychopathology: Specific effects or induction of general susceptibility? Psychological Bulletin, 130(1), 115-142.

* O'Connor, T., Heron, J., Glover, V., & the ALSPAC Study Team. (2002). Antenatal anxiety predicts child behavioral/emotional problems independently of postnatal depression. Journal of the American Academy of Child and Adolescent Psychology, 41(12), 1470-1477.

* Sagrestano, L.M., Feldman, P., Killingsworth Rini, C., Woo, G., & Dunkel-Schetter, C. (1999). Ethnicity and social support during pregnancy. American Journal of Community Psychology, 27(6), 869-898. 

* van Os, J., & Selton, J. (1998). Prenatal exposure to maternal stress and subsequent schizophrenia. British Journal of Psychiatry, 172(1), 324-326.