From Medscape Medical News > Psychiatry
Megan Brooks
January 30, 2012 — Prenatal and early childhood exposure to the organic solvent tetrachloroethylene (PCE) may raise the risk of certain psychiatric illnesses, particularly bipolar disorder, post-traumatic stress disorder (PTSD), and schizophrenia, later in life, new research shows.
The population-based, retrospective birth-cohort study showed that children in Cape Cod who were exposed to drinking water contaminated with PCE, which was used to line municipal water pipes, had almost a 2-fold increased risk for bipolar disorder compared with the general population.
The study was published online January 20 in Environmental Health.
Used widely in industry and to dry clean clothes, PCE is a well-known neurotoxin, Ann Aschengrau, ScD, and colleagues from Boston University School of Public Health in Massachusetts note in their report.
PCE readily crosses the blood-brain barrier and has a high affinity for the lipophilic tissues in the central nervous system. The exact mechanisms for its neurotoxic effects remain unclear but include peroxidation of cell membrane lipids, alterations in the fatty acid profile of the brain, and loss of myelin and interactions with neuronal receptors.
Exposure to PCE has been shown to cause mood changes, anxiety, and depression in people who work with it. To date, the long-term effect of this chemical on children exposed to PCE has been less clear, although there is some evidence that children of people who work in the dry cleaning industry have an increased risk for schizophrenia.
To investigate further, the Boston team studied individuals born between 1969 and 1983 to married women who lived in towns in Cape Cod, Massachusetts, that had vinyl-lined asbestos-cement water pipes.
Dose Response
These pipes were installed by public water companies from the late 1960s through early 1980 to solve alkalinity problems in dead-end sections of their distribution systems. The liner was applied by spraying a mixture of vinyl resin and PCE. More than a decade elapsed before officials discovered that large quantities of PCE were leaching into the public water supplies.
Surveys conducted in 1980 found that drinking water supplies in Cape Cod had PCE levels ranging from 1.5 to 7750 μ/L. Because replacing the pipes was prohibitively expensive, systematic flushing and bleeding were used to reduce levels below 40 μ/L, which was the maximum recommended level at the time. The maximum contaminant level for PCE is now set at 5 μ/L.
The Cape Cod cohort included 1512 individuals. The participants included 831 persons with both prenatal and early childhood exposure to PCE and 547 persons who had not been exposed. Participants provided information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and places of residence from the time of their birth through 1990.
PCE exposure from the vinyl-liner water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm, the authors explain.
The researchers did not see any meaningful increase in the risk for depression with prenatal and childhood PCE exposure (risk ratio [RR], 1.1; 95% confidence interval [CI], 0.9 - 1.4). This finding was "both surprising and maybe reassuring," Dr. Aschengrau told Medscape Medical News, given that earlier research in PCE-exposed adults suggested an increased risk for depressive disorders.
However, the researchers did find that individuals with any exposure during gestation and early childhood were at increased risk for bipolar disorder (RR, 1.8; 95% CI, 0.9 - 3.5) and PTSD (RR, 1.5; 95% CI, 0.9 - 2.5). Further increases in risk were observed for bipolar disorder (RR, 2.7; 95% CI, 1.3 - 5.6) and PTSD (RR,1.7; 95% CI, 0.9 - 3.2) among persons with the highest exposure levels.
The risk of schizophrenia was also elevated among exposed individuals (RR, 2.1; 95% CI, 0.2 - 20.0), but the number of cases was too small to draw reliable conclusions, the authors note.
"Risk Remains Real"
The researchers note, however, that a study published in 2007 in Schizophrenia Research found a 3.4-fold increased risk for schizophrenia (95% CI, 1.3 - 9.2) among the offspring of parents who worked as dry cleaners. Adjusting for confounding factors did not appreciably alter the finding.
Mary Perrin, DrPH, assistant professor of psychiatry and environmental medicine from the New York University Langone Medical Center in New York City, worked on that study. Medscape Medical News asked her for her thoughts on the Cape Cod study.
"No one epidemiological study is going to prove anything. You have to build evidence, and my personal opinion is that it's another brick in the wall showing that we really need tighter regulation of these substances in the environment. The animal literature is quite clear on this," said Dr. Perrin.
She added that the Cape Cod study is "methodologically a good study. The authors articulated the limitations of the study, which you can't ignore, and did not overstate the results, which are very interesting."
Dr. Aschengrau and colleagues say the limitations of their study include the possibility of exposure misclassification and a lack of data on water consumption and bathing habits; self-reported mental illness data; and possible residual confounding as a result of missing data on several risk factors for mental illness.
The low response rate is another limitation. It is possible that individuals with mental illnesses preferentially ignored requests to participate, the investigators note. This would have reduced the number of cases in the final sample. However, available evidence suggests that this did not introduce selection bias, the authors say.
Dr. Aschengrau also noted that it is not possible to calculate the exact amount of PCE the participants in the study were exposed to.
"Levels of PCE were recorded as high as 1550 times the currently recommended safe limit. While the water companies flushed the pipes to address this problem, people are still being exposed to PCE in the dry cleaning and textile industries and from consumer products, and so the potential for an increased risk of illness remains real," she said.
Dr. Aschengrau and her colleagues added that independent investigations of similarly exposed populations are needed to corroborate their findings.
The study was supported by the National Institute of Environmental Health Sciences. Study investigator David Ozonoff, MD, PhD, is Co-Editor-in-Chief of Environmental Health. Dr. Ozonoff recused himself from all decisions regarding acceptance and publication of the manuscript. In 1980, he served as a witness in bankruptcy court in a suit against the Johns-Manville Corporation, manufacturers of the vinyl-lined asbestos-cement water pipes. He has also testified in personal injury and property damage cases involving exposure to tetrachloroethylene and trichloroethylene. Three years ago, Dr. Aschengrau served as a consultant in a personal injury case involving chlorinated solvent contamination. None of the parties in any litigation supported, reviewed, or had knowledge of this study. The other authors of this study have disclosed no relevant financial relationships.
Environmental Health. 2012;11:2. Published online January 20, 2012. Abstract
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