Prenatal Alcohol, Toxin Exposure Can Cause Rapid Brain Cell Death

SEATTLE - Prenatal exposure to alcohol, club drugs and environmental toxins, such as lead, may kill fetal brain cells and cause mental health problems, including schizophrenia, later in life, say researchers from Washington University and elsewhere.

Among the research results presented in a press conference Friday at the annual meeting of the American Association for the Advancement of Science, brain scientists found that:

As few as two cocktails may kill fetal brain cells.

Women with high levels of delta-ALA, an indicator of lead exposure, in their blood, were twice as likely to have a child with schizophrenia, as women with low levels of the substance.

An estimated one in 100 live births are affected by exposure to alcohol.

"We've known for 30 years that alcohol can have deleterious effects on the developing fetal nervous system. And for 30 years we've been trying to understand why," said Dr. John W. Olney, a neuroscientist at Washington University.

In humans, the brain goes through a growth spurt, which starts toward the end of the second trimester of pregnancy and continues through the first three years of life.

During the growth spurt, new brain cells are added, connections form and dissolve between the brain cells, and some unnecessary cells are killed off.

Olney's research with infant mice indicates that brain cells called neurons are particularly vulnerable to committing suicide during the brain's growth spurt. Alcohol and drugs, such as anesthesia or anti-convulsants, interfere with neurotransmitters, including glutamate, which excites brain cells, and GABA, a brain chemical that inhibits neuron activity, Olney said. When those brain chemicals can't do their jobs, developing neurons shut down and die.

Olney and his colleagues have discovered that low levels of alcohol can accelerate brain cell suicide to two to four times the normal rate. A blood alcohol level of 0.07 - just below the legal intoxication limit - sustained for half an hour to an hour is enough to cause the brain damage. That blood alcohol level is about the equivalent of two cocktails, Olney said. The damage first appears in an area involved in controlling movement called the caudate nucleus, and in the cerebral cortex, the brain's "central intelligence agency," within four hours of alcohol exposure, Olney said.

Club drugs, such as the anesthetic ketamine - known as Special K - also can cause brain damage in developing fetuses, Olney said. Most people who use such drugs combine them with alcohol. The mixture is a recipe for brain cell suicide.

The brain damage caused by alcohol is not always readily apparent, said Ann P. Streissguth of the University of Washington. New brain imaging techniques may help researchers identify people who have damage associated with alcohol exposure in the womb, she said.

A study of 415 patients who had been diagnosed with fetal alcohol syndrome or fetal alcohol effects indicates that early brain damage can cause problems later in life.

Over 90 percent of the children, adolescents and adults in the study have mental health problems, Streissguth said. The problems range from attention deficit disorders in 60 percent of the children and adolescents, depression in 40 percent to 50 percent of the teenagers and adults, and psychotic behavior in about 30 percent of the adults. About 25 percent of adults with fetal alcohol problems had attempted suicide. And only 11 of the 90 adults in the study were able to live and work independently, Streissguth said.

The problems can extend into the next generation as well, she said. Over half of the 44 adults in the study who had become parents are no longer caring for their own children. Child protective services took children away from 36 percent of the mothers, and 45 percent of the fathers had given up raising their children, Streissguth said.

Alcohol and drugs are not the only substances that could damage the fetal brain and lead to life-long mental problems.

A study by Columbia University epidemiologist Ezra S. Susser suggests that exposure to lead during pregnancy also may cause fetal brains to commit cell suicide and may be linked to the development of schizophrenia later in life. If the results of the study hold true when repeated, it would be the first time an environmental toxin has been linked to the mental illness, Susser said. The study will appear in the journal Environmental Health Perspectives.

Susser analyzed blood samples taken from pregnant women in the years 1959 to 1966. The researchers also followed the children of those women to see which got schizophrenia.

Scientists can't measure lead levels directly in the blood, Susser said, so they determined how much of a chemical called delta-ALA, a marker for lead, was in the samples. When the researchers examined the two sets of data, they found that mothers with high levels of delta-ALA were two times more likely to have a child with schizophrenia than mothers with low levels of the chemical.

Susser cautioned that the study does not prove that prenatal exposure to lead causes schizophrenia, but may indicate that lead has previously undiscovered effects, some of which may persist long after the initial exposure.

Another study of the same group indicated that women who got the flu during the first half of pregnancy also were more likely to have children with schizophrenia, Susser said. His group also is evaluating the effect of prenatal nutrition on schizophrenia.

The studies indicate that brain cell suicide in fetuses could be activated by a variety of mechanisms, disrupting brain development and causing a wide variety of psychiatric problems decades later, the scientists said.

(c) 2004, St. Louis Post-Dispatch. Distributed by Knight Ridder/Tribune News Service.

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