Un estudio divulgó en la aplicación del septiembre de 2005 EHP encontró que había efectos significativos sobre las concentraciones del plomo de la sangre del índice de inteligencia de un niño aun cuando estaba debajo de 10 ug/dL. Sobre el lanzamiento del julio de 2005 del tercer informe nacional sobre la exposición humana a los productos químicos ambientales por la CDC, Jim Pirkle, director de diputado para la ciencia en el laboratorio ambiental de la salud de la CDC, indicado, no hay nivel seguro de la sangre [plomo] en niños.

Varios grupos también han encontrado evidencia que conducen la exposición pueden formar el comportamiento social de un niño. Una investigación ambiental divulga una correlación fuerte, datando de 1900, entre el crimen violento y el uso de la pintura conducir-basada y la gasolina plomada. La investigación complementa estudios encontró que los niveles del plomo del hueso en varones jóvenes fueron correlacionados con la agresión y la criminalidad. El plomo se asocia perceptiblemente a un riesgo para la delincuencia. (Investigación de Needleman en el noviembre el diciembre de 2002 Neurotoxicology y teratología)

Otro nuevo campo de investigación liga la exposición de plomo temprana a los cambios en el cerebro del envejecimiento. ¿Nasser Zawia, profesor de asociado de la farmacología y de la toxicología en la universidad de Rhode Island, de Kingston, y de sus colegas encontró la expresión creciente de la proteína amiloidea del precursor (APP) y de su producto? - amiloide (que es un sello de la enfermedad de Alzheimer), en las ratas del envejecimiento que fueron expuestas al plomo poco después nacimiento. ¿En cambio, las viejas ratas que fueron expuestas al plomo no demostraron una expresión creciente del APP y? - amiloide

. El trabajo, publicado en la aplicación del 26 de enero de 2005 el diario de la neurología, sugiere que la exposición al plomo temprana puede reprogramar la expresión y la regulación del gene más adelante en vida. Según Zawia, la investigación preliminar también demuestra que los monos expuestos al plomo como infantes exhiben cambios moleculares similares tan bien como la patología de Alzheimer exagerado.

Mercurio. La dosis actual de la referencia de la agencia de protección del medio ambiente (EPA) para la forma del methylmercury (un orgánico, tóxico de mercurio) es 0.1 microgramos por kilogramo por el día (ug/kg/day). Exponen a los seres humanos al methylmercury sobre todo a través de la consumición de pescados contaminados; un buen 70% de esta contaminación viene de fuentes anthropogenic tales como emisiones de centrales eléctricas con carbón. La exposición de alto nivel al methylmercury en la matriz se liga a un número de debilitaciones, incluyendo el retraso mental, a parálisis cerebral, a los asimientos, a la sordera, a la ceguera, y a las dificultades del discurso. Un artículo en la aplicación del mayo de 2005 EHP pone el coste económico a los Estados Unidos de la toxicidad methylmercury-inducida (en términos de productividad perdida) en $8.7 mil millones anualmente.

Los efectos de las exposiciones de la bajo-dosis no son tan evidentes. Dos estudios epidemiológicos grandes de las poblaciones de la pesca en las islas de Faroe y las Seychelles han producido resultados contradictorios con respecto a efectos de la bajo-dosis. Ambos estudios intentaron examinar la asociación entre la exposición del methylmercury y el neurodevelopment en los niños que madres comieron contaminó los mariscos durante embarazo.

El líder de las islas de Faroe estudia, Philippe Grandjean, profesor del adjunto de la salud ambiental en la escuela de Harvard de la salud pública, y de sus colegas divulgados en la aplicación del noviembre de 1997 Neurotoxicology y la teratología que los niños Faroese de 7 años tenían déficit cognoscitivo significativo y cambios neurológicos después de la exposición prenatal al methylmercury. El equipo de Grandjean siguió en los niños en la edad 14. Según un informe en la aplicación del febrero de 2004 el diario de la pediatría, los niños continuaron teniendo problemas, incluyendo cambios neurológicos y disminuyeron el control nervioso del corazón.

En cambio, los autores de las Seychelles estudian encontrado poca evidencia de durar daño en una cohorte de 66 mes-viejos niños, según su informe en la aplicación del 26 de agosto de 1998 JAMA. Un estudio complementario, publicado en la aplicación del 17 de mayo de 2003 el Lancet, no encontraron semejantemente ningún efecto duradero sobre lengua, la memoria, las habilidades de motor, o la función del comportamiento cuando los niños eran 9 años.

Los diversos resultados de los dos estudios están desconcertando porque los niños de ambas poblaciones aparecían ser expuestos a las cantidades similares de methylmercury. Varias explicaciones se han propuesto, incluyendo la posibilidad que las diferencias genéticas entre las poblaciones pueden alterar sus predispositions relativos para dañar de la exposición del mercurio. La fuente del methylmercury es también diferente en las dos poblaciones. Exponen a los Faroese sobre todo a través de la consumición de la carne experimental de la ballena, mientras que la población de Seychelles confía pesadamente en pescados del océano. Según Gary Myers, un profesor de la neurología y la pediatría a la universidad del centro médico de Rochester y la una de los investigadores principales de las Seychelles estudian, ballena que la carne contiene muchos otros contaminantes (PCBs incluyendo) además del methylmercury. Hay también evidencia, él dice, que los efectos de la exposición concomitante del PWB y del mercurio son sinérgicos.

Los investigadores continúan mirando si hay un peligro del methylmercury en los niveles de la exposición alcanzados por el consumo de pescados. Otra capa de incertidumbre fue agregada con los resultados publicados en la aplicación del octubre de 2005 la demostración de EHP que el consumo de pescados durante embarazo aparecía alzar la cognición infantil--pero solamente mientras el producto del mercurio, según lo medido en pelo maternal, no era demasiado alto.

La cuestión de si los niveles bajos del mercurio son dañosos también se ha manifestado en una controversia sobre el uso de las vacunas que contenían thimerosal, un preservativo. Aunque es thimerosal fue quitado de muchas de estas vacunas en 2001, los niños que fueron inmunizados antes de esa fecha habrían podido recibir una dosis acumulativa de más de 200 ug/kg del mercurio con el complemento rutinario de las vacunaciones de la niñez, según un estudio en la aplicación del mayo de 2001 la pediatría. Thimerosal es ethylmercury casi medio por peso. Porque es ethylmercury es una forma orgánica de mercurio, hay una cierta suspicacia que actúa como el methylmercury en el cerebro, aunque la investigación publicada en la aplicación del agosto de 2005 EHP sugiere que las dos formas diferencian grandemente en cómo se distribuyen a través y se eliminan del cerebro. Los países en vías de desarrollo continúan utilizando las vacunas pediátricas que contienen thimerosal. En los Estados Unidos, thimerosal todavía está presente en las vacunas de la gripe, que la CDC recomienda se dé a las mujeres embarazadas y a los niños envejecidos 6-23 meses.

Los grupos de la defensa, tales como SafeMinds, han sugerido que la subida década-larga de la diagnosis del autism está relacionada con la presencia de thimerosal en vacunas. En mayo de 2004, sin embargo, el instituto de la medicina (IOM) publicó un informe, revisión de la seguridad de la inmunización: Vacunas y Autism, indicando que varios estudios epidemiológicos publicados desde 2001 evidencias constantemente proporcionadas de ninguna asociación entre las vacunas y el autism thimerosal-que contienen. Sin embargo, el informe del IOM ha sido criticado seriamente por un número de grupos de la defensa, incluyendo la asociación nacional de Autism, para confiar demasiado pesadamente en un sistema específico de datos epidemiológicos mientras que despide la evidencia clínica y otros estudios epidemiológicos que demostraron evidencia de un acoplamiento.

A pesar de los aseguramientos del IOM, algunos científicos continúan explorando los mecanismos subyacentes los efectos neurotoxic potenciales de thimerosal. En la aplicación del enero de 2005 NeuroToxicology, el S. Jill James, un profesor de la pediatría en la universidad de Arkansas para las ciencias médicas, y sus colegas divulgan que toxicidad neuronal y glial de la célula del methylmercury y ethylmercury (según lo dosificado vía thimerosal) es ambas mediadas por el agotamiento del glutathione antioxidante del peptide. De los dos tipos de la célula, las neuronas fueron encontradas para ser particularmente susceptibles al agotamiento ethylmercury-inducido del glutathione y la muerte de la célula, según James, y el tratamiento previo de las células con glutathione redujeron estos efectos. Otros estudios de James y de sus colegas, divulgados en la aplicación del diciembre de 2004 el diario americano de la nutrición clínica, demostraron que los niños autistic hicieron los niveles inferiores del glutathione comparar a los controles normales, y pudieron por lo tanto haber tenido una reducción significativa en la capacidad de desintoxicar especie reactiva del oxígeno.

James dice que el perfil anormal sugiere que estos niños puedan tener una vulnerabilidad creciente a las exposiciones ambientales del favorable-oxidante y un umbral más bajo para el neurotoxicity y el immunotoxicity oxidative. Hablando en la conferencia internacional de XXII Neurotoxicology en septiembre de 2005, ella presentó evidencia que los polimorfismos genéticos múltiples que afectan caminos del glutathione pueden obrar recíprocamente para producir un desequilibrio metabólico crónico que podría contribuir al desarrollo y a los síntomas clínicos del autism. Su papel en el diario americano de la nutrición clínica divulgó que los niveles bajos del glutathione en muchos niños autistic eran reversibles con la intervención alimenticia apuntada, pero las ramificaciones de esto que encuentra siguen siendo confusas.

Manganese. As an essential nutrient, manganese is required for normal development; the reference dose for manganese is 0.14 mg/kg/day. Chronic occupational exposure to high levels of this metal is associated with manganism, a condition reminiscent of Parkinson disease that is characterized by tremors, rigidity, and psychosis. The illness is seem primarily among miners.

Animal studies published in the August 2005 issue of Neurotoxicology by David Dorman, director of the division of biological sciences at the CIIT Centers for Health Research in Research Triangle Park, North Carolina, suggest that the fetus is protected to a certain extent from maternally inhaled manganese. According to Dorman, children are exposed to manganese primarily by ingesting it, but he knows of no link between childhood exposure to manganese and later Parkinson disease.

Nevertheless, because manganese affects the adult brain, people suspect that the developing brain may be even more susceptible to harm from this metal, and recent research has unveiled a new cause for concern: In the January 2006 issue of EHP, child psychiatry professor Gail Wasserman and colleagues from Columbia University reported that Bangladeshi children who drank well water with high concentrations of naturally occurring manganese had diminished intellectual function. The researchers noted that the bioavailability of manganese in water is higher than that of manganese in food. They also pointed out that about 6% of U.S. wells have a high enough manganese content to potentially put some children at risk for diminished intellectual function.

The cellular and molecular mechanisms of manganese neurotoxicity are not well understood. The dopaminergic system in the basal ganglia, which is affected in Parkinson disease, may be involved, but this hypothesis is controversial. TomáGuilarte, a professor of molecular neurotoxicology at the Johns Hopkins Bloomberg School of Public Health, described research on these systems in nonhuman primates at the XXII International Neurotoxicology Conference. According to Guilarte, unpublished positron-emission tomography studies of the basal ganglia show that manganese does appear to have an effect on dopaminergic neurons. Guilarte found that the more manganese the animals received, the less dopamine was released through the actions of amphetamine (which is used to induce the release of the neurotransmitter). This does not mean that manganese causes Parkinson’s disease, merely that it has an effect on those neurons, he says. This is the first report of an in vivo effect on dopamine release by manganese.

PCBs, PBDEs, and pesticides. Many chemicals raise concerns because of their persistence in the environment and their tendency to bioaccumulate in animal tissues. They are typically synthetic molecules that were designed for use in everyday products, such as electrical equipment, computers, furniture, and pesticides.

PCBs appear to be present in all parts of the food chain, and humans are exposed to these molecules primarily through the ingestion of animal fat. The toxicity of these chemicals was first recognized after mass poisonings in Japan in 1968 and Taiwan in 1979. Children born to women who had ingested contaminated cooking oil in Taiwan had a number of developmental abnormalities, including psychomotor delay and lower scores on cognitive tests, according to a report in the 15 July 1988 issue of Science.

Since those earlier observations, several studies have described a connection between prenatal exposure to PCBs and delayed cognitive development and lower IQ. For example, a study in the 10 November 2001 Lancet reports those infants and young children exposed to PCBs through breast milk scored lower on tests of psychomotor and mental development. The mothers were exposed to normal background levels of PCBs in Europe. In response to such studies, the U.S. Food and Drug Administration set tolerance levels for PCBs in a number of consumer products, such as milk and manufactured dairy products (1.5 parts per million), poultry (3.0 parts per million), and baby food (0.2 part per million).

PBDEs are widely used as flame retardants in consumer products. The effects of PBDEs on humans is not clear, but animal toxicity studies described in volume 183 (2004) of Reviews of Environmental Contaminants and Toxicology show that PBDEs can cause permanent learning and memory impairments, hearing deficits, and behavioral changes. There is a growing concern about PBDEs because they appear to be accumulating in human tissues. Andreas Sjö, a toxicologist at the CDC, and colleagues found a trend toward increasing concentrations of PBDEs in human serum taken from sample populations in the southeastern United States from 1985 through 2002, and in Seattle, Washington, from 1999 through 2002. This report appears in the May 2004 EHP. Several studies have also discovered PBDEs in human breast milk. The current EPA reference dose for PBDEs is 2 mg/kg/day.

As for pesticides, it’s been suggested by zoologist Theo Colborn of the University of Florida that every child conceived today in the Northern Hemisphere is exposed to these chemicals from conception through gestation and beyond. Some pesticides appear to be more harmful than others, and so the reference dose varies somewhat from one compound to another.

The effects of pesticides on the developing brain have been investigated in human epidemiologic studies and in laboratory experiments with animals. Vincent Garry, a professor of environmental medicine at the University of Minnesota, and his colleagues found that children born to applicators of the fumigant phosphine were more likely to display adverse neurological and neurobehavioral developmental effects. The herbicide glyphosate was also linked to neurobehavioral effects, according to the same report, which appeared in the June 2002 issue of EHP Supplements. Another epidemiologic study, reported in the March 2005 issue of NeuroToxicology, showed that women who were exposed to organophosphate pesticides in an agricultural community in California had children who displayed adverse neurodevelopmental effects, and that higher levels of pesticide metabolites in maternal urine were associated with abnormal reflexes in the women’s newborn children.

Many PCBs, PBDEs, and pesticides are the subject of the 2001 Stockholm Convention on Persistent Organic Pollutants, which became international law in May 2004. The goal of the treaty is to rid the world of PCBs, dioxins and furans, and nine highly dangerous pesticides, according to the United Nations Environment Programme. Implementation of the treaty has significant practical challenges, however, including the difficulty of eliminating one persistent pollutant without creating another (for example, when burning PCBs yields by-products such as dioxins and furans).

Exposure to a neurotoxicant may not be the only way to disrupt the natural growth of the brain. Scientists are now looking at the subtle physiological effects of immunotoxicants and infectious agents on biological events during development.

It turns out that mothers who experience an infection during pregnancy are at a greater risk of having a child with a neurodevelopmental disorder such as autism or schizophrenia. For example, prenatal exposure to the rubella virus is associated with neuromotor and behavioral abnormalities in childhood and an increased risk of schizophrenia spectrum disorders in adulthood, according to an article in the March 2001 issue of Biological Psychiatry. Rubella has also been linked to autism: some 8-13% of children born during the 1964 rubella pandemic developed the disorder, according to a report in the March 1967 Journal of Pediatrics. The same study also noted a connection between the rubella virus and mental retardation.

Some epidemiologic studies have found an increased risk of schizophrenia among the children of women who were exposed to the influenza virus during the second trimester of pregnancy, according to a report in the February 2002 Current Opinion in Neurobiology. In the August 2004 Archives of General Psychiatry, Ezra Susser, head of epidemiology at Columbia University’s Mailman School of Public Health, and his colleagues reported that the risk of the mental disorder was increased sevenfold if the schizophrenic patient’s mother had influenza during her first trimester of pregnancy. A prospective birth cohort study in the April 2001 Schizophrenia Bulletin found that second trimester exposure to the diphtheria bacterium also significantly increased the risk of schizophrenia.

How might infectious agents cause these disorders? According to John Gilmore, a professor of psychiatry at the University of North Carolina at Chapel Hill, maternal infections during pregnancy can alter the development of fetal neurons in the cerebral cortex of rats. The mechanism is far from clear, but signaling molecules in the mother’s immune system, called cytokines, have been implicated. Speaking at the XXII International Neurotoxicology Conference, Gilmore described in vitro experiments showing that elevated levels of certain cytokines--interleukin-1?, interleukin-6 and tumor necrosis factor-alpha (TNF- --reduce the survival of cortical neurons and decrease the complexity of neuronal dendrites in the cerebral cortex. I believe that the weight of the data to date indicates [that the maternal immune response] can have harmful effects, says Gilmore.

Inflammatory responses in the mother may not be the only route to modifying the fetal brain. The University of California, Davis, Center for Children’s Environmental Health and Disease Prevention is conducting a large study of autistic children in California called CHARGE (Childhood Autism Risks from Genetics and the Environment), which suggests that the child’s immune system may also be involved. According to Pessah, the study principal investigator, children with autism appear to have a unique immune system. Autistic children have a significant reduction in plasma immunoglobulins and a skewed profile of plasma cytokines compared to other children, he says. We think that an immune system dysfunction may be one of the etiological cores of autism.

He continues, We know that many of the things that kids are exposed to these days are immunotoxicants. . . . We have evidence that ethylmercury and thimerosal alter the signaling properties of antigen-presenting cells, known as dendritic cells, at nanomolar levels. Since each dendritic cell can activate 250 T cells, any dysregulation will be magnified, he says. Add to that a genetic abnormality in processing immune information, and there could be a problem.

Such problems might extend to the central nervous system. The brains of individuals who have a neurodevelopmental disorder also show evidence of inflammation. In the January 2005 issue of the Annals of Neurology, Carlos Pardo, an assistant professor of neurology and pathology at the Johns Hopkins University School of Medicine, and his colleagues report finding high levels of inflammatory cytokines (interleukin-6, interleukin-8, and interferon-) in the cerebrospinal fluid of autistic patients. Glial cells, which serve as the brain’s innate immune system, are the primary sources of cytokines in the central nervous system. So it may not be surprising that Pardo’s team also discovered that glia are activated--showing both morphological and physiological changes--in postmortem brains of autistic patients.

The recognition that the immune system is involved in neurodevelopmental disorders is changing people’s perceptions of these conditions. Historically, scientists have focused on the role of neurons in all kinds of neurological diseases, Pardo says, but they have generally been ignoring the [glia]. He adds, In autism, it could be that the [glia] are responding to some external insult, such as an infection, an intrauterine injury, or a neurotoxicant.

According to Pardo, it’s still not clear whether the neuroimmune responses associated with autism contribute to the dysfunction of the brain or whether they are secondary reactions to some neural abnormality. John Gilmore’s work [showing that cytokines can be harmful to brain cells] is quite interesting and important, he says. However, in vitro studies may produce results that don’t reflect what occurs under in vivo conditions. Cytokines like TNF- may be beneficial for some neurobiological functions at low concentrations, but may be extremely neurotoxic at high concentrations.

The medical and scientific communities recognize the colossal challenges involved in identifying the ultimate causes of neurodevelopmental disorders. This is complicated by the sheer numbers of potential exposures involved. More than 67% of the nearly 3,000 chemical compounds produced or imported in amounts exceeding 1 million pounds per year have not been examined with even basic tests for neurotoxicity, according to Toxic Ignorance, a 1997 analysis by Environmental Defense.

In the past few years, several large projects have been proposed, and funding by the NIH has been increased. For example, the NIH boosted its support for autism research from $22 million in 1997 to $100 million in 2004. In 2001, the NIEHS and the EPA jointly announced the creation of four new children’s environmental health research centers (including the one at the University of California, Davis), which focus primarily on neurodevelopmental disorders. More recently, the proposed multibillion-dollar National Children’s Study, which is cosponsored by the Department of Health and Human Services and the EPA, has been designed to follow nearly 100,000 children over the course of 21 years. The investigators plan to study the effects of environmental factors on children’s growth and development, including impacts on learning, behavior, and mental health. Study investigators hope to enroll the first participants in early 2007.

Scientists also see the need for designing better studies. In neurodevelopmental studies, as in any other field, the quality of a study is only as good as all of its parts. Jean Harry, head of the NIEHS Neurotoxicology Group, says, You can have a valid assessment of behavior, but in the absence of good exposure data, a causative association with environmental factors will be compromised.

In a bid to address the difficulties faced by epidemiologic studies that look for neurodevelopmental effects from in utero chemical exposure, a working group of 20 experts gathered in September 2005 under the auspices of the Penn State Hershey Medical Center, coincident with the XXII International Neurotoxicology Conference. The goal of their day-long session was to develop a scheme of best practices for the design, conduct, and interpretation of future investigations, as well as the practical inclusion of new technologies, such as imaging.

At one point in the dialogue, the group recognized that perhaps the greatest challenge in these studies was determining how to evaluate in utero exposures to environmental chemicals. Quite often the very nature of epidemiological studies limits the ability to perform accurate exposure assessments, says Harry, who was part of the expert group. Such exposures may have occurred in the distant past, they may have been unknown, or they may have been in conjunction with many other compounds.

The group therefore recommended that actual measurements, even if indirect, are better than methods based on subject recall. It also recommended that a well-defined hypothesis should form the foundation of in utero studies for assessing neurodevelopmental outcomes. [These and other] conclusions will move the science forward by describing methods that should improve interstudy comparisons, and they offer ways in which research results should be reported to the scientific and medical communities, says Judy LaKind, an adjunct associate professor of pediatrics at the Hershey Medical Center and a member of the workshop steering committee. The complete workshop report will be published in an upcoming issue of NeuroToxicology.

The challenges of addressing neurodevelopmental disorders are more than scientific. The difficulties come together at a crossroads where the communication of knowledge, the treatment of patients, and the regulation of potentially toxic chemicals meet. Says Herbert, Evidence-based medicine has not yet developed standards for assessing, or practices for treating, the impacts of chronic, multiple low-dose exposures. Rather than waiting, she says, patients and parents of patients are turning to alternative medicine to address their concerns.

That’s not always a good thing, especially when patients and parents may be misinformed. Kathy Lawson, director of the Healthy Children Project at the Learning Disabilities Association of America, says there is a disconnect between scientific knowledge and the public’s awareness of ways to reduce the incidence of some disorders. In my visits to various organizations, I’ve discovered that people are completely unaware that there is a connection between environmental toxicants and their health, she says. Even pediatricians often don’t know about these things, she adds.

Educating the public is only part of the solution. Elise Miller, executive director of the nonprofit Institute for Children’s Environmental Health, thinks that federal regulatory agencies do not adequately protect children’s health. The Toxic Substances Control Act, which was passed thirty years ago, needs a major overhaul to ensure neurotoxicants and other chemicals are prioritized, screened, and tested properly, she says. Currently, there are too many chemicals on the market and in the products we use every day for which there is no toxicity data.

Some politicians agree with these sentiments. In July 2005, Senator Frank R. Lautenberg (D-NJ) introduced the Child, Worker, and Consumer Safe Chemicals Act, which initially calls for chemical manufacturers to provide health and safety information on the chemicals used in certain consumer products, among them baby bottles, water bottles, and food packaging. If passed into law, the bill, coauthored by Senator James Jeffords (I-VT), would require all commercially distributed chemicals to meet the new safety measures by 2020.

The human brain is often touted as the most complex structure in the known universe. The developmental process that produces this remarkable entity may also be among the most delicate in nature. As one scientist put it, The brain doesn’t like to be jerked around. That kind of fragility makes it difficult for scientists to untangle genetic influences from what often may be subtle environmental assaults. Even so, the catalogue of harmful environmental agents will undoubtedly continue to grow as scientists learn more about the interactions between the developing brain and its environment. The hope is that enough good minds will use that catalogue to create a future with healthier brains and more peace of mind for parents and society alike.

US: About 17% of school-age children in the United States suffer from a disability that affects their behavior, memory, or ability to learn, according to a study published in the March 1994 issue of Pediatrics by a team from the Centers for Disease Control and Prevention (CDC). The list of maladies includes attention deficit/hyperactivity disorder (ADHD), autistic spectrum disorders, epilepsy, Tourette syndrome, and less specific conditions such as mental retardation and cerebral palsy. All are believed to be the outcome of some abnormal process that unfolded as the brain was developing in utero or in the young child.

These disorders have an enormous impact on families and society. According to the 1996 book Learning Disabilities: Lifelong Issues, children with these disorders have higher rates of mental illness and suicide, and are more likely to engage in substance abuse and to commit crimes as adults. The overall economic cost of neurodevelopmental disorders in the United States is estimated to be $81.5-167 billion per year, according to a report published in the December 2001 issue of EHP Supplements.

Potentially even more disturbing is that a number of epidemiologic studies suggest that the incidence of certain disorders is on the rise. In the United States, the diagnosis of autistic spectrum disorders increased from 4-5 per 10,000 children in the 1980s to 30-60 per 10,000 children in the 1990s, according to a report in the August 2003 Journal of Autism and Developmental Disorders. Similarly, notes a report in the February 2002 issue of CNS Drugs, the diagnosis of ADHD grew 250% between 1990 and 1998. The number of children in special education programs classified with learning disabilities increased 191% between 1977 and 1994, according to an article in Advances in Learning and Behavioral Disabilities, Volume 12, published in 1998.

So what is going on? The short answer is that no one really knows. There’s not even consensus on what the soaring rates actually mean. Heightened public awareness could account for the surge in the numbers, or it may be that physicians are getting better at diagnosing the conditions. Some autism researchers believe the rise in that condition’s prevalence simply reflects changes in diagnostic criteria over the last 25 years. On the other hand, some scientists believe that the rates of neurodevelopmental disease are truly increasing, and that the growing burden of chemicals in the environment may play a role.

With that in mind, investigators are considering the effects of gene-environment interactions. A child with a mild genetic tendency toward a neurodevelopmental disorder might develop without clinically measurable abnormalities in the absence of environmental hits. However, children in industrialized nations develop and grow up in a veritable sea of xenobiotic chemicals, says Isaac Pessah, director of the University of California, Davis, Center for Children’s Environmental Health and Disease Prevention. Fortunately, he says, most of us have a host of defense mechanisms that protect us from adverse outcomes. However, genetic polymorphisms, complex epistasis, and cytogenetic abnormalities could weaken these defenses and amplify chemical damage, initiating a freefall into a clinical syndrome.

Pessah cites the example of autism. He says susceptibility for autism is likely conferred by several defective genes, no one of which can account for all the core symptoms of social disinterest, repetitive and overly focused behaviors, and problems in communication. Could multiple genetic liabilities and exposure to a chemically complex environment act in concert to increase the incidence and severity of the condition?

Despite the uncertainties, many scientists believe it would be wise to err on the side of caution when it comes to a research agenda. As Martha Herbert, a pediatric neurologist at Harvard Medical School, puts it, Even though we may have neither consensus nor certainty about an autism epidemic, there are enough studies coming in with higher numbers that we should take it seriously. Environmental hypotheses ought to be central to research now. The physiological systems that have been harmed by environmental factors may also point to treatment targets, and this might be a great way to help the children.