Severe emotional stress during the first delicate months of a woman's pregnancy may permanently impair the neurodevelopment of her unborn child, leading to an increased risk of schizophrenia later in life, new research suggests.
The link between maternal stress and fetal development is not new: A study in the Lancet in 2000 suggested, for example, that a mother's stress during pregnancy may increase the risk of congenital brain malformations in her baby. And it has been well established that severe maternal stress is associated with low birth weight and premature birth. Now, a new study by British and Danish researchers in this week's Archives of General Psychiatry examines the impact of stress the acute, agonizing kind, such as that experienced with death or sickness in the mother's immediate family, and not the run-of-the-mill anxiety of daily life on the future psychiatric health of her offspring.
The study group consisted of 1.38 million births recorded in Denmark, from 1973 to 1995. Children were followed from age 10 until their death, their departure from Denmark, the onset of schizophrenia or the end of the study period in 2005. Researchers determined also whether the birth mothers had suffered extreme stress due either to the death or illness (heart attack, cancer or stroke) of a first-degree relative six months prior to and at any time during pregnancy. The data showed that women who experienced a close family member's death during the first three months of pregnancy had a 67% increased risk of having a child who would develop schizophrenia later in life. Stress before pregnancy or in late pregnancy had no such effect; neither did stress associated with a family member's illness.
Intuitively, it makes sense that death would have an impact that illness did not. "The problem with diagnoses of heart disease and that kind of thing is that it's likely that there has been worry about the health of that individual for some time," says the study's author, Kathryn Abel of the Centre for Women's Health Research at the University of Manchester. "Once somebody gets admitted with a heart attack or stroke or a serious illness, in some way there is relief because they're being managed it might not be such an acute event, which we know death to be, even when someone has been ill for a long time. When they die, that's it."
If the severity of maternal stress matters, then one would expect the death of child to cause more injury than the death of a parent. Indeed, says Abel, her data hinted at such a response compared with women who lost a parent, those who lost a child appeared to have a higher likelihood of giving birth to a child at risk for schizophrenia but her sample size was too small to confirm the theory.
How the mother's emotional stress impacts her fetus's growth is still mostly a mystery. It's possible that increased levels of the stress hormone cortisol interfere directly with fetal development. Or it may be that the mother's stress response triggers a cascade of other chemical changes in her immune system, in blood levels of sex hormones, or perhaps in cell-signaling proteins called cytokines that may indirectly affect early fetal development. Whatever the exact mechanism, its effects lend credence to the theory that starting early in pregnancy, "mothers transmit information to their fetus about what condition they're likely to be born into whether they're going to be thrifty and expect to be in a relative state of starvation, for example, or whether they can expect plenty a clear evolutionary advantage," says Abel. "But it may be that in some settings, it has an adverse consequence because it restricts the growth of the fetus, and perhaps causes abnormal development of the brain, which makes it more susceptible to diseases, such as schizophrenia."
Though the current study looked only at schizophrenia risk, Abel and her collaborators at the University of Aarhus believe that maternal stress may have a similar effect on the risk of other conditions, among them depression and other mental disorders, along with social consequences such as the risk of criminal conviction or the likelihood of marriage, "things that tend to cluster in the deprived," says Abel. "We have not shown that this is specific to schizophrenia. We've just only looked at schizophrenia."
Abel hopes to replicate her findings in Sweden with a bigger study population and richer data, including the socio-economic status of mothers. "Social class is one of the big, enduring predictors of risk of mental illness. The lower the social class the higher the risk. You're born with this risk," says Abel.
The other big congenital risk factor is genetics, first-degree family history being the most powerful risk factor for schizophrenia. And, in fact, the new study found that the added risk associated with maternal stress disappeared in children whose mothers already had a family history of mental illness showing once again that the interplay of environment and genes is anything but straightforward.