If a woman is anxious for months at a time—say she's in a troubled marriage or is financially strapped—high levels of the stress hormone cortisol may reach her fetus. Such a fetus doesn't need as many brain receptors to sense the hormone's presence, so it develops fewer. But having fewer cortisol receptors changes a person's ability to cope in later life. The cortisol system has its own shut-off valve; when cortisol levels in the bloodstream reach a certain point, the body stops making the hormone and everything returns to normal. But people with fewer receptors don't sense that it's time to stop making cortisol until they're practically swimming in it. Living with high levels of cortisol not only creates wear and tear on the body but also makes it tough to handle strong emotions without lashing out or withdrawing, and it may set people up for depression.
Infants whose pregnant mothers developed posttraumatic stress disorder after the September 11 attacks were found to be more easily upset by loud noises and unfamiliar people. "Temperament is not only genetically determined," says Catherine Monk, a Columbia University psychologist. "It is constructed throughout early development and, in part, in utero by exposure to the mother's mood." In a study of thousands of women in England, those who ranked in the top 15 percent for anxiety during pregnancy had children with double the rate of emotional and behavioral problems at 10 years old.
Stress may cause long-term cognitive deficiencies, too. Coe subjects pregnant monkeys to three loud car-horn bursts at unpredictable intervals over a 10-minute period, and he does it daily for one-quarter of their pregnancy. "Certainly women living in the Congo or in Iraq have a much more stressful pregnancy than anything I ever studied," he says. Yet even this moderate amount of stress results in infant monkeys that are less able to hold up their heads or scrutinize novel objects. At three years old, their hippocampus, a brain area responsible for learning and memory, is 10 percent smaller than normal, which likely translates into worse functioning.
Just as challenges can bring out the best in adults, prenatal stress seems to benefit children sometimes: Two-year-olds whose mothers were moderately anxious or depressed during pregnancy performed better than average on reasoning and coordination tasks such as solving puzzles, stacking blocks, and manipulating small objects. It may be that moderately emotionally "charged" women provided a more varied intrauterine environment, with stimulations that sped up brain development.
On the other hand, one of the scariest risks for stressed-out pregnant women is the greater chance that their child will one day be schizophrenic. Israeli girls who were in their second month in the womb during the 1967 Arab-Israeli war were 4.3 times more likely to become schizophrenic than girls born at other times, and boys were 1.2 times more likely to develop the disease. Another study found that children of women who experienced the death of a close relative during the first trimester of pregnancy were also more likely to later develop schizophrenia.
Researchers speculate that the placenta is very sensitive to stress hormones coursing through a severely stressed-out mother's body, and that those hormones cause alterations in the fetal brain that help unleash schizophrenia down the line.
<!--put comment to force the end tag of span-->The First Forty Days
if a woman gets the flu during her first trimester, her child is seven times as likely to develop schizophrenia as a teenager or young adult. It may not be the flu itself that causes the malfunction, but rather an immunological reaction. Cytokines—proteins the mother's body produces in response to the flu—get transmitted to the fetus and harm its brain.
What is really intriguing is that mice that were given a specific cytokine, interleukin-6, gave birth to offspring who not only displayed schizophrenic-like behaviors but also behaviors analogous to those seen in autistic humans.
A 2008 study suggests that 12 to 15 percent of autism cases may occur because maternal autoantibodies—antibodies that a person makes against something in themselves—interfere with proteins in the fetal brain. After identifying unusual antibodies in women who had more than one autistic child, researchers injected the antibodies into four pregnant monkeys. They also gave antibodies taken from women with healthy children to another four pregnant monkeys. The offspring of the monkey mothers who received the regular antibodies were fine, but all four of those whose mothers got the unusual autoantibodies spontaneously developed bizarre tics, such as pacing and doing repeated backflips. "Repetition of motor behaviors is one of the three cardinal features of autism," says David Amaral, a neuroscientist at the M.I.N.D. Institute at the University of California, Davis, who headed the study. Scientists don't know under which conditions these autoantibodies form, nor why they do so.
They do know that a critical window for development is 20 to 40 days after fertilization. During that time, fetuses that eventually develop autism or schizophrenia often begin to display shared physical characteristics, such as protruding ears and unusual toes.
A groundbreaking idea could hold the answer to the puzzle of why some children are autistic while others become schizophrenic. Researchers Bernard Crespi and Christopher Badcock argue that a struggle between genes from Dad's sperm and Mom's eggs results in different expressions of the same genes. When a genetic region that plays a role in brain development is disrupted, the theory says, if the genes inherited from the father dominate, the disruption gives rise to autism, whereas if the genes inherited from the mother dominate, the interference will result in schizophrenia.
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