Prenatal exposure to lead may be linked to the development of schizophrenia in young adulthood, according to a study by Columbia University Medical Center researchers and others. The study is one of the first prospective studies of a prenatal chemical exposure as a risk factor for an adult psychiatric disease.
Researchers at CUMC, the New York State Psychiatric Institute, and Kaiser Permanente Health Care analyzed second-trimester blood serum samples from a group of people born in Oakland, Calif., between 1959 and 1966, says Dr. Mark Opler, postdoctoral research fellow in the Department of Psychiatry and first author of the paper. In the 1950s and 60s, lead exposure in California was relatively high because leaded gasoline was still in use.
The investigators compared levels of a biological marker for lead exposure with a diagnosis of schizophrenia years later. The study of 44 people diagnosed with schizophrenia and 75 people without the disease all were born at Kaiser Foundation Health Plan clinics.
They found that people with elevated levels of the biological marker, delta-aminolevulinic acid, were about twice as likely to receive a diagnosis of schizophrenia as young adults as those with lower levels, says Dr. Ezra Susser, professor and chairman of epidemiology at the Mailman School of Public Health and head of epidemiology of brain disorders at NYSPI.
"The results are preliminary because of the small numbers, but they are important, because they raise the possibility that lead-induced damage to the developing brain may show itself decades after the exposure," Dr. Susser says. "Dr. Opler is already collecting data for a further study which will enlarge the sample size."
The researchers say more study is needed because their results, when adjusted for confounding factors associated with both lead exposure and schizophrenia (such as parental age, socioeconomic status, maternal smoking or alcohol use), only approached statistical significance, which makes it difficult to draw definitive conclusions.
The results were presented Feb. 13 at the 2004 American Association for the Advancement of Science meeting and were published in the January 2004 online version of the journal Environmental Health Perspectives.
By studying families in which more than one person has Alzheimer's disease, Columbia University Medical Center researchers have found that genes play a strong role in memory function.
Determining how genes influence memory is an important intermediate step toward finding the genetic basis of memory and Alzheimer's disease.
"The results are exciting because if we can identify the genes that are responsible for memory, they may lead us to identifying more of the genes that contribute to Alzheimer's," says Dr. Joseph H. Lee, assistant professor of epidemiology at the Mailman School and first author of the study, which appeared in the Feb. 10 issue of the journal Neurology.
The researchers studied about 1,000 people from more than 250 families affected by Alzheimer's disease, primarily in the Dominican Republic and Puerto Rico. The investigators tested all study participants for memory, attention, abstract reasoning, language, and visual-spatial ability, analyzing results to determine how much of the individual's ability in those areas was due to genetics.
"We found that about half of the variation in memory performance among individuals is due to genetics," says Dr. Richard Mayeux, Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Epidemiology and senior author. "The other half is due to environmental factors such as education. But the influence of genetics was not as strong in the areas of attention, abstract reasoning, language, and visual-spatial ability."
Because one form of the ApoE gene increases the risk of developing Alzheimer's, the researchers controlled for the influence of ApoE. They found evidence that ApoE does not have much effect on memory performance, Dr. Lee says.
More research is needed to determine whether the study results apply to people without multiple family members with Alzheimer's disease.
Bruises from clumsiness and stumbling are some of the first signs of a rare, inherited neurodegenerative disease called Niemann-Pick Type C (NPC). As children grow older, walking and swallowing become increasingly difficult and vision and hearing deteriorate. Many die in their teens or earlier, although the age of onset varies, even within families.
No treatments can slow the disease's progression, which is usually blamed on faulty cholesterol transport within cells. But CUMC researchers now believe hidden lipid transport pathways may exist in cells and may provide clues needed to develop effective therapies. The research was published in the Feb. 16 Journal of Cell Biology.
At the same time, the researchers have also found that faulty cholesterol transport is probably not the ultimate culprit behind the disease. Cholesterol has been blamed because it gets stuck in the cells' lysosomes and can't be used by the cell for making membranes or growth factors for the brain.
Instead, Dr. Steven Sturley, professor of pediatrics in the Institute of Human Nutrition, and his colleagues have fingered faulty transport of sphingolipids another integral component of the cell membrane that also accumulate in lysosomes.
They base their conclusion on studies with yeast, which have the gene that causes NPC. When the researchers put the yeast's NPC gene into mammalian cells lacking their own endogenous gene, both cholesterol and sphingolipid problems were prevented. Since the yeast protein only transports sphingolipids in yeast, Dr. Sturley says, "we think the protein's primary role in people is moving sphingolipids out of the lysosome, and cholesterol, which binds tightly to sphingolipids, just goes for the ride. It points to sphingolipids as a way to a possible therapy, not cholesterol."
The researchers also saw that yeast cells can thrive without the NPC gene, suggesting that yeast have hidden sphingolipid pathways that bypass the NPC gene. If the same pathways exist in people, they may provide new targets for therapies.
Dr. Marc Patterson, professor of clinical neurology and pediatrics and director of pediatric neurology, is testing a new drug in a children's clinical trial that blocks sphingolipid synthesis. The same treatment slows the disease's progression in lab animals.