Study hints that prenatal toxins can trigger psychiatric disease.
Babies exposed to lead in the womb may be at increased risk of developing schizophrenia as adults, US researchers have revealed.
Scientists know that toxins such as lead and alcohol can harm a mother's unborn child and trigger developmental problems during childhood. But the new study is one of the first to show that this damage can precipitate disorders that strike decades later. Schizophrenia is usually diagnosed in the late teens or early twenties.
Ezra Susser of Columbia University, New York and his team tested stored blood samples collected from expectant California mothers between 1959 and 1966. They compared the blood lead levels of 44 women whose children went on to develop schizophrenia with 75 others whose children did not.
Offspring of mothers whose blood topped 150 micrograms of lead per litre were twice as likely to develop schizophrenia as those whose blood levels were below this threshold, Susser revealed at the American Association for the Advancement of Science meeting in Seattle, and in an online paper1.
If the finding holds up in other groups, as many as a quarter of all schizophrenia cases in this same age group might be explained by lead, Susser suggests. In the 1950s and 60s, lead exposure in California was relatively high because of the use of leaded gasoline, he says.
Most petrol is unleaded today. But lead still leaches into the environment from industrial smelters and paint, and Ezra says it might still account for a significant chunk of schizophrenia cases in developing countries. "We think it's a very important finding," he says.
Suicidal brain cells
Susser suspects that lead may kill nerve cells in a fetus's growing brain. Doctors know that prenatal exposure to the toxin can cause childhood mental retardation and other brain deficits, but they are unsure exactly how lead causes injury.
In the past few years, animal research has shown that drugs that dampen brain-cell activity - such as alcohol, certain anaesthetics and anti-epileptic drugs - prompt cells to commit suicide. Brain cells are thought to be particularly vulnerable from mid-pregnancy through the first two or three years of a baby's life.
Even a single dose of alcohol or some anaesthetics can wipe out a swathe of nerve cells in this way, says John Olney of Washington University School of Medicine in St Louis, Missouri.
Olney has found that a blood alcohol level equivalent to that after a couple of cocktails, maintained for just half an hour or more, can double or quadruple the number of brain cells dying off in a mouse's growing fetus. It is not yet known if alcohol has the same effect in humans.
Ezra says he now hopes to examine whether fetuses exposed to alcohol or other drugs are also at increased risk of schizophrenia or other psychiatric disorders as adults. He also has preliminary evidence that an influenza infection during the first half of pregnancy boosts the risk of schizophrenia in adults, he says.
Opler, M. G. A. et al. Prenatal lead exposure, -aminolevulinic acid, and schizophrenia. Environmental Health Perspectives, doi:10.1289/ehp.6777, (2004).