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Monday, March 31, 2014

Chronic Stress in Early Life Causes Anxiety, Aggression in Adulthood, Neurobiologists Find

From ScienceDaily
via Cold Spring Harbor Laboratory

March 27, 2014

Summary: In experiments to assess the impacts of social stress upon adolescent mice, both at the time they are experienced and during adulthood, a laboratory team conducted many different kinds of stress tests and means of measuring their impacts. The research indicates that a 'hostile environment in adolescence disturbs psycho-emotional state and social behaviors of animals in adult life,' the team says.

"The exposure to a hostile environment during their adolescence
had profound consequences in terms of emotional state
and the ability to interact with peers,"
Dr. Enikolopov observes of the mice in this study.

In recent years, behavioral neuroscientists have debated the meaning and significance of a plethora of independently conducted experiments seeking to establish the impact of chronic, early-life stress upon behavior -- both at the time that stress is experienced, and upon the same individuals later in life, during adulthood.

These experiments, typically conducted in rodents, have on the one hand clearly indicated a link between certain kinds of early stress and dysfunction in the neuroendocrine system, particularly in the so-called HPA axis (hypothalamic-pituitary-adrenal), which regulates the endocrine glands and stress hormones including corticotropin and glucocorticoid.

Yet the evidence is by no means unequivocal. Stress studies in rodents have also clearly identified a native capacity, stronger in some individuals than others, and seemingly weak or absent in still others, to bounce back from chronic early-life stress. Some rodents subjected to early life stress have no apparent behavioral consequences in adulthood -- they are disposed neither to anxiety nor depression, the classic pathologies understood to be induced by stress in certain individuals.

Today, a research team led by Associate Professor Grigori Enikolopov of Cold Spring Harbor Laboratory (CSHL) reports online in the journal PLoS One the results of experiments designed to assess the impacts of social stress upon adolescent mice, both at the time they are experienced and during adulthood. Involving many different kinds of stress tests and means of measuring their impacts, the research indicates that a "hostile environment in adolescence disturbs psychoemotional state and social behaviors of animals in adult life," the team says.

The tests began with 1-month-old male mice -- the equivalent, in human terms of adolescents -- each placed for 2 weeks in a cage shared with an aggressive adult male. The animals were separated by a transparent perforated partition, but the young males were exposed daily to short attacks by the adult males. This kind of chronic activity produces what neurobiologists call social-defeat stress in the young mice. These mice were then studied in a range of behavioral tests.

"These experiments showed that in young mice chronic social defeat induced high levels of anxiety, helplessness, diminished social interaction, and diminished ability to communicate with other young animals."

"The tests assessed levels of anxiety, depression, and capacity to socialize and communicate with an unfamiliar partner," explains Enikolopov. These experiments showed that in young mice chronic social defeat induced high levels of anxiety, helplessness, diminished social interaction, and diminished ability to communicate with other young animals. Stressed mice also had less new nerve-cell growth (neurogenesis) in a portion of the hippocampus known to be affected in depression: the subgranular zone of the dentate gyrus.

Another group of young mice was also exposed to social stress, but was then placed for several weeks in an unstressful environment. Following this "rest" period, these mice, now old enough to be considered adults, were tested in the same manner as the other cohort.

In this second, now-adult group, most of the behaviors impacted by social defeat returned to normal, as did neurogenesis, which retuned to a level seen in healthy controls. "This shows that young mice, exposed to adult aggressors, were largely resilient biologically and behaviorally," says Dr. Enikolopov.

However, in these resilient mice, the team measured two latent impacts on behavior. As adults they were abnormally anxious, and were observed to be more aggressive in their social interactions. "The exposure to a hostile environment during their adolescence had profound consequences in terms of emotional state and the ability to interact with peers," Dr. Enikolopov observes.

Journal Reference

Irina L. Kovalenko, Anna G. Galyamina, Dmitry A. Smagin, Tatyana V. Michurina, Natalia N. Kudryavtseva, Grigori Enikolopov. Extended Effect of Chronic Social Defeat Stress in Childhood on Behaviors in Adulthood. PLoS ONE, 2014; 9 (3): e91762 DOI: 10.1371/journal.pone.0091762

The Importance of Playdates and Kids with Autism

From Parents Magazine

By Lisa Quinones-Fontanez
March 12, 2014

This is a post in (Parents Magazine's) weekly Autism Hopes series by Lisa Quinones-Fontanez, a mom who blogs over at Atypical Familia (formerly AutismWonderland).


“Play is often talked about as if it were a relief from serious learning. But for children play is serious learning. Play is really the work of childhood.”
-- Fred Rogers

My son, Norrin, playing
with his friend, Dylan.
When my son, Norrin, was first diagnosed with autism he had no appropriate play skills. He didn’t even have much interest in playing with other children. Norrin was content playing by himself. I never pushed playdates because our schedules consisted of work, school and therapy. Most of the other special needs parents I know juggle the same kind of schedule. So working on socialization and playdates with peers wasn’t a priority for us especially since we knew it was being done at school.

A few weeks ago,
I hosted a party and invited a few moms with their children. It was our first party in years. And it was the first time I had other kids with autism in our home. Unsure of how to host while entertaining children, I asked our ABA therapist if she could help out for a few hours.

I’ve seen Norrin at the playground. Sometimes he’ll run around with another kid but it’s never for more than ten minutes. I’ve seen him in school sitting beside a classmate but not really engaging. Watching Norrin interact with kids in his own environment was eye opening for me. Norrin was talking and sharing and wanting to play with the other kids. He even read his guests a story.

At eight years old, Norrin is finally ready for playdates. And since our little party, he’s been asking for all his friends to come over and play.

I’m no longer tied to mainstream dreams. I just want Norrin to be happy and
be as independent as he can. I also want him to have at least one friend. A friendship will never form unless I start cultivating the value and meaning of a friend now.

A few weeks ago I shared that
I was ready to start cutting back on our therapy. I’ve spent the last five years focusing on all the skills I thought were more important, always putting socialization on the back burner. It’s time to take play seriously.

Do your children have regular playdates?

Sunday, March 30, 2014

New Parenting Study Released

From The New Yorker's Blog "Shouts & Murmurs"

By Sarah Miller
March 24, 2014

A recent study has shown that if American parents read one more long-form think piece about parenting they will go fucking ape shit.

The study was conducted by Susan Waterson, a professor of behavioral psychology at the University of Massachusetts and the author of zero books, because, Waterson says, “another book at this point would just be cruel.”

In the course of seven weeks, Waterson interviewed a hundred and twenty-seven families about their reaction to articles that begin with a wryly affectionate parenting anecdote, segue into a dry cataloguing of sociological research enlivened with alternately sarcastic and tender asides, and end with another wryly affectionate anecdote that aims to add a touch of irony or, failing at that, sentimentality.

“I wasn’t looking to prove there was too much of this content,” Waterson said. “I’m a behaviorist, not a sociologist. Only one part of this equation interested me—the fucking-ape-shit part.”

Her study was focussed on families in central Massachusetts, but her findings were echoed by parents across the country.

Frieda Duntmore, a thirty-nine-year-old Baltimore-high-school teacher and the mother of twin six-year-old girls, recounted standing in line at a supermarket, reading a magazine article about how being a parent sucked, and then recalling that, that very morning, she’d read another article, which said that being a parent was awesome, and that anyone who didn’t have kids might as well just take their own life.

“All of a sudden, I felt my skull start to split right down the middle. I put my hand up, and there was literally blood there.” Duntmore paid for her groceries and fled. “About fifteen minutes later, my skull pieced itself back together, so I figured I’d forget about it,” she said.

Paul Nickman, forty-five, was taking a coffee break at his Visalia, California, law office when he began to leaf through an article about the importance of giving kids real challenges. “They mentioned this thing called grit, and I was like, ‘O.K, great. Grit.’ Then I started to think about how, last year, I’d read that parents were making kids do too much and strive too hard, and ever since then we’ve basically been letting our kids, who are ten and six, sit around and stare into space.”

Nickman called his wife and started to shout, “Make the kids go outside and get them to build a giant wall out of dirt and lawn furniture and frozen peas!” He added, “Get them to scale it, and then make them go to the town zoning board to get it permitted, but don’t let them know it was your idea!” Nickman has no idea how many minutes passed before he realized he was standing in a fountain outside a European Waxing Center, rending his clothes.

During Nickman’s three-day-long stay at U.C.L.A.’s psych ward, his wife, Anne, forty-four, brought him a pile of newspapers, one of which happened to briefly mention Waterson’s study. “I was so relieved,” Nickman said. “I turned to Anne and said, ‘I think I was just going fucking ape shit, that’s all.’ And Anne said, ‘I think I might be going fucking ape shit, too.’ ”

The Nickmans and Duntmore both got in touch with Waterson, and, following her advice, they began a protocol of recovery. They cancelled their Facebook accounts, and they go online only when absolutely necessary. If they leave their house, they wear horse blinders, which Waterson’s husband, an inventor, has adapted for human use, and which can be purchased on Waterson’s Web site.

Upon greeting other parents, they hand out pre-printed cards (also available on their Web site) that read, “Please do not talk to me about my children or your children, or children, or schools, or schooling, or learning, or Tae Kwon Do, ballet., etc. Also, please ignore the horse blinders.”

“Most people just smile and walk away,” Duntmore said. “But, once in a while, someone wants to talk about Crimea, which is a treat.”

America is Poisonous to Your Health

From TomDispatch
via Salon

By David Rosner and Gerald Markowitz

April 29, 2013

Without our knowledge or consent, some of the country's largest corporations are subjecting us to deadly toxins.

A hidden epidemic is poisoning America. The toxins are in the air we breathe and the water we drink, in the walls of our homes and the furniture within them. We can’t escape it in our cars. It’s in cities and suburbs. It afflicts rich and poor, young and old. And there’s a reason why you’ve never read about it in the newspaper or seen a report on the nightly news: it has no name — and no antidote.

The culprit behind this silent killer is lead. And vinyl. And formaldehyde. And asbestos. And Bisphenol A. And polychlorinated biphenyls (PCBs). And thousands more innovations brought to us by the industries that once promised “better living through chemistry,” but instead produced a toxic stew that has made every American a guinea pig and has turned the United States into one grand unnatural experiment.

Today, we are all unwitting subjects in the largest set of drug trials ever. Without our knowledge or consent, we are testing thousands of suspected toxic chemicals and compounds, as well as new substances whose safety is largely unproven and whose effects on human beings are all but unknown.

The Centers for Disease Control (CDC) itself has begun monitoring our bodies for 151 potentially dangerous chemicals, detailing the variety of pollutants we store in our bones, muscle, blood, and fat.

None of the companies introducing these new chemicals has even bothered to tell us we’re part of their experiment. None of them has asked us to sign consent forms or explained that they have little idea what the long-term side effects of the chemicals they’ve put in our environment — and so our bodies — could be. Nor do they have any clue as to what the synergistic effects of combining so many novel chemicals inside a human body in unknown quantities might produce.

How Industrial Toxins Entered the American Home

The story of how Americans became unwitting test subjects began more than a century ago. The key figure was Alice Hamilton, the “mother” of American occupational medicine, who began documenting the way workers in lead paint pigment factories, battery plants, and lead mines were suffering terrible palsies, tremors, convulsions, and deaths after being exposed to lead dust that floated in the air, coating their workbenches and clothes.

Soon thereafter, children exposed to lead paint and lead dust in their homes were also identified as victims of this deadly neurotoxin. Many went into convulsions and comas after crawling on floors where lead dust from paint had settled, or from touching lead-painted toys, or teething on lead-painted cribs, windowsills, furniture, and woodwork.

Instead of leveling with the public, the lead industry through its trade group, the Lead Industries Association, began a six-decade-long campaign to cover-up its product’s dire effects. It challenged doctors who reported lead-poisoned children to health departments, distracted the public through advertisements that claimed lead was “safe” to use, and fought regulation of the industry by local government, all in the service of profiting from putting a poison in paint, gasoline, plumbing fixtures, and even toys, baseballs, and fishing gear.

As Joe Camel would be for tobacco, so the little Dutch Boy of the National Lead Company became an iconic marketing tool for Dutch Boy Lead Paint, priming Americans to invite a dangerous product into their children’s playrooms, nurseries, and lives. The company also launched a huge advertising campaign that linked lead to health, rather than danger. It even produced coloring books for children, encouraging them to paint their rooms and furniture using lead-based paint.

Only after thousands of children were poisoned and, in the 1960s, activist groups like the Young Lords and the Black Panthers began to use lead poisoning as a symbol of racial and class oppression did public health professionals and the federal government begin to rein in companies like the Sherwin-Williams paint company and the Ethyl Corporation, which produced tetraethyl lead, the lead-additive in gasoline. In 1971, Congress passed the Lead Paint Poisoning Prevention Act that limited lead in paint used for public housing. In 1978, the Consumer Products Safety Commission finally banned lead in all paints sold for consumer use. During the 1980s, the Environmental Protection Agency issued rules that led to the elimination of leaded gasoline by 1995 (though it still remains in aviation fuel).

The CDC estimates that in at least 4 million households in the U.S. today children are still exposed to dangerous amounts of lead from old paint that produces dust every time a nail is driven into a wall to hang a picture, a new electric socket is installed, or a family renovates its kitchen. It estimates that more than 500,000 children ages one to five have “elevated” levels of lead in their blood. (No level is considered safe for children.) Studies have linked lost IQ points, attention deficit disorders, behavioral problems, dyslexia, and even possibly high incarceration rates to tiny amounts of lead in children’s bodies.

Unfortunately, when it came to the creation of America’s chemical soup, the lead industry was hardly alone. Asbestos is another classic example of an industrial toxin that found its way into people’s homes and bodies. For decades, insulation workers, brake mechanics, construction workers, and a host of others in hundreds of trades fell victim to the disabling and deadly lung diseases of asbestosis or to lung cancer and the fatal cancer called mesothelioma when they breathed in dust produced during the installation of boilers, the insulation of pipes, the fixing of cars that used asbestos brake linings, or the spraying of asbestos on girders. Once again, the industry knew its product’s dangers early and worked assiduously to cover them up.

Despite growing medical knowledge about its effects (and increasing industry attempts to downplay or suppress that knowledge), asbestos was soon introduced to the American home and incorporated into products ranging from insulation for boilers and piping in basements to floor tiles and joint compounds. It was used to make sheetrock walls, roof shingles, ironing boards, oven gloves, and hot plates. Soon an occupational hazard was transformed into a threat to all consumers.

Today, however, these devastating industrial-turned-domestic toxins, which destroyed the health and sometimes took the lives of hundreds of thousands, seem almost quaint when compared to the brew of potential or actual toxins we’re regularly ingesting in the air we breathe, the water we drink, and the food we eat.

Of special concern are a variety of chlorinated hydrocarbons, including DDT and other pesticides that were once spread freely nationwide, and despite being banned decades ago, have accumulated in the bones, brains, and fatty tissue of virtually all of us. Their close chemical carcinogenic cousins, polychlorinated biphenyls (PCBs), were found in innumerable household and consumer products — like carbonless copy paper, adhesives, paints, and electrical equipment – from the 1950s through the 1970s. We’re still paying the price for that industrial binge today, as these odorless, tasteless compounds have become permanent pollutants in the natural environment and, as a result, in all of us.

The Largest Uncontrolled Experiment in History

While old houses with lead paint and asbestos shingles pose risks, potentially more frightening chemicals are lurking in new construction going on in the latest mini-housing boom across America. Our homes are now increasingly made out of lightweight fibers and reinforced synthetic materials whose effects on human health have never been adequately studied individually, let alone in the combinations we’re all subjected to today.

Formaldehyde, a colorless chemical used in mortuaries as a preservative, can also be found as a fungicide, germicide, and disinfectant in, for example, plywood, particle board, hardwood paneling, and the “medium density fiberboard” commonly used for the fronts of drawers and cabinets or the tops of furniture. As the material ages, it evaporates into the home as a known cancer-producing vapor, which slowly accumulates in our bodies. The National Cancer Institute at the National Institutes of Health suggests that homeowners “purchasing pressed-wood products, including building material, cabinetry, and furniture… should ask about the formaldehyde content of these products.”

What’s inside your new walls might be even more dangerous. While the flame retardants commonly used in sofas, chairs, carpets, love seats, curtains, baby products, and even TVs, sounded like a good idea when widely introduced in the 1970s, they turn out to pose hidden dangers that we’re only now beginning to grasp. Researchers have, for instance, linked one of the most common flame retardants, polybrominated diphenyl ethers, to a wide variety of potentially undesirable health effects including thyroid disruption, memory and learning problems, delayed mental and physical development, lower IQ, and the early onset of puberty.

Other flame retardants like Tris (1,3-dichloro-2-propyl) phosphate have been linked to cancer. As the CDC has documented in an ongoing study of the accumulation of hazardous materials in our bodies, flame retardants can now be found in the blood of “nearly all” of us.

Nor are these particular chemicals anomalies. Lurking in the cabinet under the kitchen sink, for instance, are window cleaners and spot removers that contain known or suspected cancer-causing agents. The same can be said of cosmetics in your makeup case or of your plastic water bottle or microwavable food containers. Most recently, Bisphenol A (BPA), the synthetic chemical used in a variety of plastic consumer products, including some baby bottles, epoxy cements, the lining of tuna fish cans, and even credit card receipts, has been singled out as another everyday toxin increasingly found inside all of us.

Recent studies indicate that its effects are as varied as they are distressing. As Sarah Vogel of the Environmental Defense Fund has written, “New research on very-low-dose exposure to BPA suggests an association with adverse health effects, including breast and prostate cancer, obesity, neurobehavioral problems, and reproductive abnormalities.”

Teflon, or perfluorooctanoic acid, the heat-resistant, non-stick coating that has been sold to us as indispensable for pots and pans, is yet another in the list of substances that may be poisoning us, almost unnoticed. In addition to allowing fried eggs to slide right onto our plates, Teflon is in all of us, according to the Science Advisory Board of the Environmental Protection Agency, and “likely to be carcinogenic in humans.”

These synthetic materials are just a few of the thousands now firmly embedded in our lives and our bodies. Most have been deployed in our world and put in our air, water, homes, and fields without being studied at all for potential health risks, nor has much attention been given to how they interact in the environments in which we live, let alone our bodies.

The groups that produce these miracle substances — like the petrochemical, plastics, and rubber industries, including major companies like Exxon, Dow, and Monsanto – argue that, until we can definitively prove the chemical products slowly leaching into our bodies are dangerous, we have no “right,” and they have no obligation, to remove them from our homes and workplaces. The idea that they should prove their products safe before exposing the entire population to them seems to be a foreign concept.

In the 1920s, the oil industry made the same argument about lead as an additive in gasoline, even though it was already known that it was a dangerous toxin for workers. Spokesman for companies like General Motors insisted that it was a “gift of God,” irreplaceable and essential for industrial progress and modern living, just as the lead industry argued for decades that lead was “essential” to produce good paint that would protect our homes.

Like the oil, lead, and tobacco industries of the twentieth century, the chemical industry, through the American Chemistry Council and public relations firms like Hill & Knowlton, is fighting tooth and nail to stop regulation and inhibit legislation that would force it to test chemicals before putting them in the environment.

In the meantime, Americans remain the human guinea pigs in advanced trials of hundreds if not thousands of commonly used, largely untested chemicals. There can be no doubt that this is the largest uncontrolled experiment in history.

To begin to bring it under control would undoubtedly involve major grassroots efforts to push back against the offending corporations, courageous politicians, billions of dollars, and top-flight researchers. But before any serious steps are likely to be taken, before we even name this epidemic, we need to wake up to its existence.

A toxic dump used to be a superfund site or a nuclear waste disposal site. Increasingly, however, we – each and every one of us — are toxic dumps and for us there’s no superfund around, no disposal plan in sight. In the meantime, we’re walking, talking biohazards and we don’t even know it.

Saturday, March 29, 2014

Read Parent's Facebook Response to 'Ridiculous' Common Core Math Homework

From Yahoo! Shine's Healthy Living

By Elise Solé
March 26, 2014

 A Facebook update from a father frustrated with the Common Core math program at his son's school is making the Internet rounds after the father Jeff Severt expressed (via what looks like a kid's homework assignment) how convoluted the teaching approach is.

The worksheet posted to Facebook shows the elaborate Common Core (CC) formula for solving a math problem (as opposed to the simple strategy of subtracting the smaller number from the larger one).

It instructs the student to explain why a fictional kid named "Jack" should be using common core strategies to solve the problem: “Jack used the number line below to solve 427 - 316. Find his error. Then write a letter to Jack telling him what he did right, and what he should do to fix his mistake.”

Severt's response reads:

“Dear Jack, Don’t feel bad. I have a Bachelor of Science Degree in Electronics Engineering, which included extensive study in differential equations and other higher math applications. Even I cannot explain the Common Core mathematics approach, nor get the answer correct. In the real world, simplification is valued over complication. Therefore, 427 - 316 = 111. The answer is solved in under 5 seconds — 111. The process used is ridiculous and would result in termination if used. Sincerely, Frustrated Parent.”

The Facebook post (which by Tuesday had generated 4,400 likes, 4,300 shares, and 700 comments debating the issue) coincides with news that on Monday, Indiana became the first state to formally withdraw from the Common Core standards.

If you haven’t heard of the Common Core program, it’s an education initiative funded and developed by two Washington, D.C.-based trade organizations, the Council of Chief State School Officers (CCSSO) and the National Governors Association (NGA). According to a story published Tuesday by the Washington Post, the program is not an official federal mandate, but it has become a hot-button issue among certain political groups that either support or oppose the idea.

The program aims to ensure that all children are equally prepared as they advance to the next level by dictating what exactly students in kindergarten through 12th grade should know in arts, language, and math by the time they complete each grade. The Common Core's website states that the program focuses on "developing the critical-thinking, problem-solving, and analytical skills students will need to be successful."

Here is one example illustrated by U.S. News & World Report: Students mostly read material on par with their grade levels, not their reading ability. To help kids who are lacking comprehension, teachers use a technique called "close reading," focusing on one vocabulary word for the entire class. And thought-based questions, such as: “Why did the North fight the Civil War?,” would be swapped for fact-based ones, such as: “Who are the fathers [that Lincoln mentions]?” Other examples: Prioritizing nonfiction over literary fiction classics, and class discussions focused on evidence from the reading as opposed to creative thought.

Critics call the program a
“one-size-fits-all” approach to learning that ignores cultural and individual differences. They also argue that not all students are ready to advance at the same time, that the CC’s teaching methods overly complicate basic subjects, and that the program limits teachers from freely shaping their curricula.

Another complaint: The program doesn’t properly prepare students for the future — according to retired University of Arkansas Professor Sandra Stotsky, CC founder Professor Jason Zimba admitted in March, 2010 at a Massachusetts Board of Elementary and Secondary Education meeting that being “prepared for college” meant being ready for a nonselective two-year community college, not a selective four-year institution.

In December, an outspoken
mother testified at the Arkansas Board of Education that the Common Core program overcomplicated simple math problems. As an example, she gave the board a basic fourth-grade division problem which CC requires students to solve by using 108 steps. And in November, a Tennessee teen criticized Common Core during a school board meeting, saying, "Somewhere our Founding Fathers are turning in their graves — pleading, screaming, and trying to say to us that we teach to free minds." Videos of both speeches went viral.

According to the Associated Press, Indiana has pulled out of the Common Core program in exchange for new guidelines, on which the State Board of Education will vote next month. However, some say the new proposal is too similar to the Common Core. And while CC has been adopted by 45 states (now excluding Indiana), more than 200 bills were introduced in 2014 that would slow or stop its implementation or stop it. Oklahoma is one state considering banning the program.

In the meantime, parents like Severt will continue to struggle helping their kids with homework.

No Longer Junk: Role of Long Noncoding RNAs in Autism Risk

From ScienceDaily
via The Simons Foundation Autism Research Initiative

March 24, 2014

Summary: RNA acts as the intermediary between genes and proteins, but the function of pieces of RNA that do not code for protein has, historically, been less clear. Researchers have ignored these noncoding RNAs until recently for not complying with the central dogma of biology -- that a straight line runs from gene to RNA (transcription) to protein (translation). However, noncoding RNAs are emerging as important regulators of diverse cellular processes with implications for numerous human disorders.

In the past decade, long noncoding RNAs (lncRNAs), which extend
longer than 200 nucleotides, have emerged as additional important
players in the control of gene expression. They fine-tune the expression
of numerous genes and direct the activity of complex regulatory
pathways, often in a cell- and developmental-stage-specific manner.

Credit: Julia Yellow

RNA acts as the intermediary between genes and proteins, but the function of pieces of RNA that do not code for protein has, historically, been less clear. Researchers have ignored these noncoding RNAs until recently for not complying with the central dogma of biology -- that a straight line runs from gene to RNA (transcription) to protein (translation). However, noncoding RNAs are emerging as important regulators of diverse cellular processes with implications for numerous human disorders.

Extensive research has already examined the function of microRNAs, a category of small evolutionarily conserved noncoding RNAs about 22 to 24 nucleotides in length that target protein-coding genes in a sequence-specific manner. A plethora of microRNAs are important for brain function and neuropsychiatric diseases, including autism1.

In the past decade, long noncoding RNAs (lncRNAs), which extend longer than 200 nucleotides, have emerged as additional important players in the control of gene expression. They fine-tune the expression of numerous genes and direct the activity of complex regulatory pathways, often in a cell- and developmental-stage-specific manner.

They are found in many places in the genome: within genes, near gene regulatory regions or by themselves (intergenic noncoding RNAs). lncRNAs may overlap with the genetic code for a protein or be expressed in the opposite, or antisense, direction.

In addition to the diversity in their biogenesis, lncRNAs exhibit an impressive versatility of molecular functions. These range from passive influence on the transcription of nearby genes to limiting expression to a paternal or maternal chromosome, a process called imprinting, and inactivating one copy of the X chromosome.

They also interact with chromatin-modifying complexes, which regulate gene expression by changing the packaging of DNA, and with transcription factors that directly regulate gene expression. They may influence RNA splicing, stability and localization and play a role in the translation of RNA to protein and in protein activation. Finally, they may 'sponge' up certain microRNAs, thus blocking their function.

Molecular Multitaskers

The ability of lncRNAs to engage in such molecular multitasking may allow them to link multiple risk factors for genetic disorders into functional networks. This makes them attractive candidates for autism spectrum disorders, which are characterized either by interactions of multiple genes or by disruptions in a single gene that influences numerous molecular pathways.

Whether whole-genome DNA sequencing data will reveal strong genetic links with lncRNAs, as it has for microRNAs, is not yet clear. One thing, though, remains certain: We can no longer overlook such a substantial and active chunk of the transcriptome and characterize it as 'junk' or 'transcriptional noise' if we hope to fully understand complex disorders such as autism.

In the past few years, studies have found alterations in lncRNAs in brains from people with autism, suggesting that they contribute to autism risk. For example, MSNP1AS, a lncRNA transcribed from a region of chromosome 5 that carries an autism-associated variant, is elevated in the cortex of people with autism who also carry the disease-related variant. MSNP1AS may regulate moesin, a gene important for the structure of neurons' signal-receiving branches, or dendrites, and immune system activation.

Last year, a carefully conducted study identified numerous lncRNAs that are robustly dysregulated in autism postmortem brain samples. Impressively, some disease-altered lncRNAs are found near important autism-linked genes such as BDNF and SHANK2.

Another lncRNA with potential implications for autism is LOC389023, which regulates DPP10, a gene linked to autism and other neurodevelopmental disorders. DPP10 controls the structure and function of neuronal junctions, or synapses, via its effects on potassium ion channels3.

Last year, researchers used a similar approach to study the expression of lncRNAs in a mouse model of Rett syndrome. One lncRNA (AK081227) that is expressed at abnormal levels in these mice controls the expression of its host protein-coding gene, the gamma-aminobutyric acid receptor subunit Rho 2 (GABRR2), which has also been linked to autism.

Additional reports have linked other lncRNAs to autism, such those that travel antisense to the FMR1 and UBE3A genes. Mutations in these genes underlie fragile X syndrome and Angelman syndrome, respectively. Other studies have also uncovered a subset of lncRNAs expressed from the autism-linked PTCHD1 gene and the 7q31 chromosomal region.

In addition, the lncRNA ZNF127AS has altered expression in the brains of people with Prader-Willi syndrome. On a similar note, a cluster of small nucleolar RNAs -- which despite their name are a category of lncRNAs -- are encoded by the paternally inherited microdeletion at 15q11.2 that is also linked to Prader-Willi syndrome.

Brain Builders

Previous work has identified a subset of lncRNAs that are important for regulating the birth of new neurons, or neurogenesis, and the process by which synapses adapt to experience, called synaptic plasticity.

Of particular importance is the finding that the intergenic noncoding RNA MALAT1, one of the most highly expressed lncRNAs in the brain, can regulate the formation of new synapses, or synaptogenesis. It does this by associating inside the nucleus with multiple RNA splicing factors and influencing the expression of autism-linked genes, such as NLGN1.

Intriguingly, there are several other links between MALAT1 and autism-associated factors. For example, beta-catenin -- an important component of the WNT signaling pathway that has been linked to multiple neuropsychiatric disorders -- activates MALAT1 transcription. CREB, another transcription factor known for its role in activity-dependent gene expression, also binds to MALAT1.

Notably, CREB may control MALAT1 transcription following exposure to the peptide hormone oxytocin, which has also been linked to autism.

MALAT1 and another lncRNA, BDNFOS, which has the antisense, or opposite, code to that of the autism-linked BDNF gene, are expressed in conjunction with neuronal activity. On the other hand, GOMAFU, a lncRNA whose levels are dampened in postmortem brains from people with schizophrenia, is significantly suppressed following the activation of mouse cortical neurons.

Other lncRNAs run antisense to important synaptic plasticity-related genes, such as NRGN, CAMK2N1 and CAMKK1. lncRNAs are also associated with genes linked to changes in the synapse that occur after exposure to cocaine. Interestingly, a novel subset of lncRNAs are expressed from the regulatory elements of genes, such as c-FOS and ARC, that regulate gene transcription in response to neuronal activity.

Adding to their important role in brain plasticity, lncRNAs are highly expressed during prenatal neurogenesis and are important for maintaining and differentiating the precursors to neurons: neural stem cells and neuronal progenitors. Of particular interest is the lncRNA EVF2, which runs antisense to the regulator gene DLX5,6 and plays a crucial role in the birth of neurons that dampen brain activity. This adds another layer to the role of lncRNAs in cell-type-specific neuronal functions.

Despite these many threads, much more work is needed to determine the exact mechanisms of action and the physiological significance of lncRNAs for autism and other neurodevelopmental disorders.

Friday, March 28, 2014

Autism Rates Soar, Now Affects 1 in 68 Children

From USA Today

By Karen Weintraub
March 27, 2014

Autism rates climbed nearly 30% between 2008 and 2010, and have more than doubled since the turn of the century, according to a new study from the U.S. Centers for Disease Control and Prevention. The condition is now believed to affect one of every 68 8-year-olds – up from one in 88 just two years earlier.

That means virtually every grade in every elementary school has at least one child with autism – a seemingly astonishing rise for a condition that was nearly unheard of a generation ago.

What's still unknown is the driver of that increase. Many experts believe the rise is largely due to better awareness and diagnosis rather than a true increase in the number of children with the condition.

"We don't know the extent those factors explain in terms of the increase, but we clearly know they do play a role," said Dr. Coleen Boyle, director of the National Center on Birth Defects and Developmental Disabilities at the CDC. "Our system tells us what's going on. It (only) gives us clues as to the why."

The aging of parents is also known to be a factor; the chances of autism increase with the age of parents at conception.

"But that's not the whole story is it?" said Robert Ring, chief science officer for Autism Speaks, a research and advocacy group. Whether something in the environment could be causing the uptick remains "the million-dollar question," Ring said.

Despite their concern, experts said they were not surprised by the increase, because other data had suggested the numbers would continue to climb. In New Jersey, for instance, autism rates were 50% higher than in the rest of the nation in 2000, and they remained that much higher in 2010 – suggesting the national rates will continue to rise to catch up, said Walter Zahorodny, a psychologist who directs the New Jersey Autism Study.

"To me, it seems like autism prevalence can only get higher," he said.

The new study also showed that blacks continue to lag behind whites and Hispanics in diagnoses. Zahorodny, also an assistant professor at Rutgers New Jersey Medical School, said the gap has persisted for so long that he thinks it may be real – that blacks may be less vulnerable to autism for some unknown reason. Others are quicker to blame lack of medical access for the difference.

"We know that there are significant under-diagnosis problems in minority communities and among women and girls," said Ari Ne'eman, a member of the National Council on Disability and president of the Autistic Self-Advocacy Network. The group tries to empower autistic people to advocate for themselves.

The new CDC numbers show five times more boys with autism than girls. The girls and blacks who have intellectual disabilities as well as autism are getting counted, but the smarter kids are not, said Ne'eman, who has autism himself. "Many of the cases that are easier to miss are being missed in those populations."

To be diagnosed on autism spectrum, someone must have deficits in three areas: communications, social skills and typical behavior. Roughly one-third of the children in the CDC study also had intellectual deficits, with the remainder showing normal or above-average intelligence.

To come up with its new figures, the CDC reviewed medical and school records from 2010 at 11 different sites across the country. There is a huge range in autism prevalence across those sites, from one child in 175 found with autism in Alabama, to one in 46 in New Jersey. Boyle said the difference may be explained, at least in part, by differences in community resources for identifying and serving children with autism. Other reporting sites were in Arizona, Arkansas, Colorado, Georgia, Maryland, Missouri, North Carolina, Utah and Wisconsin.

The CDC has used the same method to determine autism prevalence every two years since 2000, showing a 120% increase in autism rates between 2000 and 2010.

The average age a child is diagnosed with autism has fallen, but remains above age 4 – though diagnosis is possible by age 2. Research suggests that the earlier a child with autism receives therapy the better the chance of limiting their deficits.

The message to parents is that if they have concerns about their child's early play, speech or movement, they should raise those concerns with with doctors and caregivers, Boyle said.

Prevalence rates quickly become fodder for politics. Several members of Congress and advocacy groups took the opportunity Thursday to promote continued funding for autism treatment and research. The $780 million Combatting Autism Act is currently up for renewal.

"This is a loud message to people in Washington that we need leadership here," said Liz Feld, president of Autism Speaks. "A national strategy that addresses all the needs of the autism community across the lifespan is what is needed now more than ever."

Others criticized the suggestion that the rising numbers reflect an "epidemic" of autism. Instead, Ne'eman argued: "Autism is something that we're born with, that always existed."

Disorganized Patches in the Brain Suggest Prenatal Origin of Autism

From HighlightHEALTH
via NIMH - The National Institute of Mental Health

March 27, 2014

The architecture of the autistic brain is speckled with patches of abnormal neurons, according to research partially funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Recently published in the New England Journal of Medicine, the study suggests that brain irregularities in children with autism can be traced back to prenatal development [1].

Thomas R. Insel, M.D., director of NIMH, said:

"While autism is generally considered a developmental brain disorder, research has not identified a consistent or causative lesion. If this new report of disorganized architecture in the brains of some children with autism is replicated, we can presume this reflects a process occurring long before birth. This reinforces the importance of early identification and intervention."

Eric Courchesne, Ph.D. and Rich Stoner, Ph.D., of the Autism Center of Excellence at the University of California, San Diego joined colleagues from the Allen Institute for Brain Science to investigate the cellular architecture of the brain’s outermost structure, the cortex, in children with autism. Courchesne recently reported an overabundance of neurons in the prefrontal cortex of children with autism.

For the current study, the researchers analyzed gene expression in postmortem brain tissue from children with and without autism, all between 2 and 15 years of age.

As the prenatal brain develops, neurons in the cortex differentiate into six layers. Each is composed of particular types of brain cells with specific patterns of connections. The research team focused on genes that serve as cellular markers for each of the cortical layers as well as genes that are associated with autism.

The study found that the markers for several layers of the cortex were absent in 91 percent of the autistic case samples, as compared to 9 percent of control samples. Further, these signs of disorganization were not found all over the brain’s surface, but instead were localized in focal patches that were 5-7 millimeters (0.20-0.28 inches) in length and encompassed multiple cortical layers.

These patches were found in the frontal and temporal lobes of the cortex — regions that mediate social, emotional, communication, and language functions. Considering that disturbances in these types of behaviors are hallmarks of autism, the researchers conclude that the specific locations of the patches may underlie the expression and severity of various symptoms in a child with the disorder.

The patchy nature of the defects may explain why early treatments can help young infants and toddlers with autism improve. According to the researchers, since the faulty cell layering does not occur over the entire cortex, the developing brain may have a chance to rewire its connections by sidestepping the pathological patches and recruiting cells from neighboring brain regions to assume critical roles in social and communication functions.


Stoner et al. Patches of disorganization in the neocortex of children with autism. New England Journal of Medicine. 2014 Mar 27.

Children Learn Aggressive Ways of Thinking and Behaving from Violent Video Games, Study Finds

From ScienceDaily

March 24, 2014

Summary: Children who repeatedly play violent video games are learning thought patterns that will stick with them and influence behaviors as they grow older, according to a new study. The effect is the same regardless of age, gender or culture. The lead researcher says it is really no different than learning math or to play the piano.
Iowa State researchers found that over time children who repeatedly
play violent video games will start to think and act more aggressively.

Children who repeatedly play violent video games are learning thought patterns that will stick with them and influence behaviors as they grow older, according to a new study by Iowa State University researchers. The effect is the same regardless of age, gender or culture. Douglas Gentile, an associate professor of psychology and lead author of the study published in JAMA Pediatrics, says it is really no different than learning math or to play the piano.

"If you practice over and over, you have that knowledge in your head. The fact that you haven't played the piano in years doesn't mean you can't still sit down and play something," Gentile said.

"It's the same with violent games -- you practice being vigilant for enemies, practice thinking that it's acceptable to respond aggressively to provocation, and practice becoming desensitized to the consequences of violence."

Researchers found that over time children start to think more aggressively. And when provoked at home, school or in other situations, children will react much like they do when playing a violent video game. Repeated practice of aggressive ways of thinking appears to drive the long-term effect of violent games on aggression.

"Violent video games model physical aggression," said Craig Anderson, Distinguished Professor of psychology and director of the Center for the Study of Violence at Iowa State and co-author of the report. "They also reward players for being alert to hostile intentions and for using aggressive behavior to solve conflicts. Practicing such aggressive thinking in these games improves the ability of the players to think aggressively. In turn, this habitual aggressive thinking increases their aggressiveness in real life."

The study followed more than 3,000 children in third, fourth, seventh and eighth grades for three years. Researchers collected data each year to track the amount of time spent playing video games, the violent content of the game and changes in a child's behavior. The length and size of the study made it possible for researchers to detect and test even small effects.

Boys reported doing more physically aggressive behaviors and spending more time playing violent games than girls. However, even when researchers controlled for gender, the violent video game effects on behavior were the same for girls and boys.

To test whether violent games had a greater effect on children who were more aggressive, researchers compared children with high and low levels of aggression. Much like gender, they did not find a significant difference in terms of the effect from violent games.

"The results make a pretty strong argument that gender and age really don't affect this relationship between video game play, aggressive thinking and aggressive behavior," said Sara Prot, a graduate student in psychology at Iowa State. "There are lasting effects on thinking and behavior. You can't say one group, because of their gender, age or culture, is protected from the effects in some special way."

Children Learn Both Good and Bad Behavior

More than 90 percent of children and teens play video games, and researchers say the majority of those games contain some type of violent content. However, that does not mean all games are bad and that children will only develop bad habits. These latest results build upon a previous study, published in Psychological Science, that analyzed the influence of prosocial media.

That earlier cross-cultural study, led by Prot, Gentile and Anderson, found that prosocial media -- video games, movies or TV shows that portray helpful, caring and cooperative behaviors -- positively influence behavior regardless of culture. The study, the first of its kind, tested levels of empathy and helpfulness of thousands of children and adolescents in seven countries. In combination, these studies show that the content of the video games youth play -- prosocial or antisocial -- determines their impact on real world behavior.

Journal Reference

Douglas A. Gentile, Dongdong Li Angeline Khoo, Sara Prot, Craig A. Anderson. Mediators and Moderators of Long-term Effects of Violent Video Games on Aggressive BehaviorPractice, Thinking, and Action. JAMA Pediatrics, March 24, 2014 DOI: 10.1001/jamapediatrics.2014.63

Thursday, March 27, 2014

CDC Telebriefing Today: CDC Releases New autism Spectrum Disorder Data

From the Centers for Disease Control

March 27, 2014

The CDC will host a telephone-only media briefing today to discuss the MMWR (Morbidity and Mortality Weekly Report) surveillance summary on the prevalence of autism spectrum disorders. Delivering the briefing will be Coleen Boyle, Ph.D., M.S., director of the CDC's National Center on Birth Defects and Developmental Disabilities.

The public is invited; one need not be a member of the media to participate.

When:   Thursday, March 27 at 12:00 noon, ET

Dial-In:  Media - (888) 795-0855
                     Non-Media - (800) 369-1917
                     International - (1-630) 395-0353

Passcode: CDC MEDIA

Important Instructions: If you would like to ask a question during the call, press *1 on your touchtone phone. Press *2 to withdraw your question. You may queue up at any time. You will hear a tone to indicate your question is pending.

A transcript of this discussion will be available following the briefing at CDC’s website:

The Toxins That Threaten Our Brains

From The Atlantic

By James Hamblin
March 18, 2014

Leading scientists recently identified a dozen chemicals as being responsible for widespread behavioral and cognitive problems. But the scope of the chemical dangers in our environment is likely even greater. Why children and the poor are most susceptible to neurotoxic exposure that may be costing the U.S. billions of dollars and immeasurable peace of mind.

Forty-one million IQ points. That’s what Dr. David Bellinger determined Americans have collectively forfeited as a result of exposure to lead, mercury, and organophosphate pesticides. In a 2012 paper published by the National Institutes of Health, Bellinger, a professor of neurology at Harvard Medical School, compared intelligence quotients among children whose mothers had been exposed to these neurotoxins while pregnant to those who had not. Bellinger calculates a total loss of 16.9 million IQ points due to exposure to organophosphates, the most common pesticides used in agriculture.

Last month, more research brought concerns about chemical exposure and brain health to a heightened pitch. Philippe Grandjean, Bellinger’s Harvard colleague, and Philip Landrigan, dean for global health at Mount Sinai School of Medicine in Manhattan, announced to some controversy in the pages of a prestigious medical journal that a “silent pandemic” of toxins has been damaging the brains of unborn children. The experts named 12 chemicals—substances found in both the environment and everyday items like furniture and clothing—that they believed to be causing not just lower IQs but ADHD and autism spectrum disorder. Pesticides were among the toxins they identified.

Jackie Lay
“So you recommend that pregnant women eat organic produce?” I asked Grandjean, a Danish-born researcher who travels around the world studying delayed effects of chemical exposure on children.

“That’s what I advise people who ask me, yes. It’s the best way of preventing exposure to pesticides.” Grandjean estimates that there are about 45 organophosphate pesticides on the market, and “most have the potential to damage a developing nervous system.”

Landrigan had issued that same warning, unprompted, when I spoke to him the week before. “I advise pregnant women to try to eat organic because it reduces their exposure by 80 or 90 percent,” he told me. “These are the chemicals I really worry about in terms of American kids, the organophosphate pesticides like chlorpyrifos.”

For decades, chlorpyrifos, marketed by Dow Chemical beginning in 1965, was the most widely used insect killer in American homes.

Then, in 1995, Dow was fined $732,000 by the EPA for concealing more than 200 reports of poisoning related to chlorpyrifos. It paid the fine and, in 2000, withdrew chlorpyrifos from household products. Today, chlorpyrifos is classified as “very highly toxic” to birds and freshwater fish, and “moderately toxic” to mammals, but it is still used widely in agriculture on food and non-food crops, in greenhouses and plant nurseries, on wood products and golf courses.

Landrigan has the credentials of some superhero vigilante Doctor America: a Harvard-educated pediatrician, a decorated retired captain of the U.S. Naval Reserve, and a leading physician-advocate for children's health as it relates to the environment. After September 11, he made news when he testified before Congress in disagreement with the EPA’s assessment that asbestos particles stirred into clouds of debris were too small to pose any real threat. Landrigan cited research from mining townships (including Asbestos, Quebec) and argued that even the smallest airborne asbestos fibers could penetrate deeply into a child’s lungs.

Chlorpyrifos is just one of 12 toxic chemicals Landrigan and Grandjean say are having grim effects on fetal brain development. Their new study is similar to a review the two researchers published in 2006, in the same journal, identifying six developmental neurotoxins. Only now they describe twice the danger: The number of chemicals that they deemed to be developmental neurotoxins had doubled over the past seven years. Six had become 12. Their sense of urgency now approached panic.

“Our very great concern,” Grandjean and Landrigan wrote, “is that children worldwide are being exposed to unrecognized toxic chemicals that are silently eroding intelligence, disrupting behaviors, truncating future achievements and damaging societies.”

The chemicals they called out as developmental neurotoxins in 2006 were methylmercury, polychlorinated biphenyls, ethanol, lead, arsenic, and toluene. The additional chemicals they’ve since found to be toxins to the developing brains of fetuses—and I hope you’ll trust me that these all are indeed words—are manganese, fluoride, chlorpyrifos, tetrachloroethylene, polybrominated diphenyl ethers, and dichlorodiphenyltrichloroethane.

Grandjean and Landrigan note in their research that rates of diagnosis of autism spectrum disorder and ADHD are increasing, and that neurobehavioral development disorders currently affect 10 to 15 percent of births. They add that “subclinical decrements in brain function”—problems with thinking that aren’t quite a diagnosis in themselves—“are even more common than these neurobehavioral development disorders.”

In perhaps their most salient paragraph, the researchers say that genetic factors account for no more than 30 to 40 percent of all cases of brain development disorders:

"Thus, non-genetic, environmental exposures are involved in causation, in some cases probably by interacting with genetically inherited predispositions. Strong evidence exists that industrial chemicals widely disseminated in the environment are important contributors to what we have called the global, silent pandemic of neurodevelopmental toxicity."

Silent pandemic. When public health experts use that phrase—a relative and subjective one, to be deployed with discretion—they mean for it to echo.

When their paper went to press in the journal The Lancet Neurology, the media responded with understandable alarm:

“A ‘Silent Pandemic’ of Toxic Chemicals Is Damaging Our Children’s Brains, Experts Claim”

-- Minneapolis Post, 2/17/14

“Researchers Warn of Chemical Impacts on Children,”
-- USA Today, 2/14/14

“Study Finds Toxic Chemicals Linked to Autism, ADHD”
-- Sydney Morning Herald, 2/16/14

When I first saw these headlines, I was skeptical. It wasn’t news that many of the chemicals on this list (arsenic, DDT, lead) are toxic. With each of these substances, the question is just how much exposure does it take to cause real damage. For instance, organophosphates aren’t something that anyone would categorically consider safe, in that they are poison. They kill insects by the same mechanism that sarin gas kills people, causing nerves to fire uncontrollably. But like asbestos, they are still legally used in U.S. commerce, with the idea that small amounts of exposure are safe.

The adage “the dose makes the poison” may be the most basic premise of toxicology. And hadn’t we already taken care of lead? Didn’t we already know that alcohol is bad for fetuses? Wasn’t fluoride good for teeth?

I found that the real issue was not this particular group of 12 chemicals. Most of them are already being heavily restricted. This dozen is meant to illuminate something bigger: a broken system that allows industrial chemicals to be used without any significant testing for safety. The greater concern lies in what we’re exposed to and don’t yet know to be toxic.

Federal health officials, prominent academics, and even many leaders in the chemical industry agree that the U.S. chemical safety testing system is in dire need of modernization. Yet parties on various sides cannot agree on the specifics of how to change the system, and two bills to modernize testing requirements are languishing in Congress. Landrigan and Grandjean’s real message is big, and it involves billion-dollar corporations and Capitol Hill, but it begins and ends with the human brain in its earliest, most vulnerable stages.

How Toxins Destroy Brains

About a quarter of your body’s metabolism goes toward operating and maintaining your brain. In order to process even basic information, billions of chemical signals are constantly being carried between neurons. The undertaking is so onerous that even though your brain is not moving (like, say, the powerful muscles in your legs), it uses around 10 times more calories per pound than the rest of you.

Most of that industrious brain and its 86 billion neurons were created in a matter of months. During the first few weeks of gestation, when your mother knew you only as morning sickness and you were a layer of cells huddled in one corner of her uterus, those cells lined up, formed a groove, and then closed to form a tube. One end of that tube eventually became your tiny spinal cord. The rest expanded to form the beginnings of your brain.

For a brain to develop properly, neurons must move to precise places in a precise sequence. They do so under the direction of hormones and chemical neurotransmitters like acetylcholine. The process is an intricate, fast-paced dance on a very tiny scale. Each nerve cell is about one hundredth of a millimeter wide, so it has to travel its own width 25,000 times just to move an inch—which some neurons in the cortex must. At any point, that cell can be knocked off course. Some of the neurotoxins Grandjean and Landrigan discuss have the potential to disrupt this journey, in a slight or serious fashion.

By the third trimester, the surface of the brain begins folding itself into wrinkled peaks and valleys, the gyri and sulci that make a brain look like a brain. Specific areas of that cortex learn to process specific aspects of sensation, movement, and thought, and that starts in the uterus. As Grandjean explains this process in his 2013 book Only One Chance, “Usage promotes function and structure, as the connectivity of the brain cells is shaped by responses to environmental stimuli.”

That is, the fetal brain starts having experiences that form the basis for learning and memory. The nature-nurture duality begins at conception.

By age two, almost all of the billions of brain cells that you will ever have are in their places. Except in the hippocampus and one or two other tiny regions, the brain does not grow new brain cells throughout your life. When brain cells die, they are gone. So its initial months of formation, when the brain is most vulnerable, are critical. “During these sensitive life stages,” Grandjean and Landrigan write, exposure “can cause permanent brain injury at low levels that would have little or no adverse effect in an adult.”

Federal health officials are aware of this risk. The National Institutes of Health, as Landrigan puts it, “finally woke up in the late 1990s to the fact that children are much more sensitive and vulnerable to chemicals than adults are.” Over the past decade, the federal government has invested substantially more money in looking at just how pregnant women and children have been affected by industrial chemicals. The EPA has awarded millions of dollars in related research grants, and the NIH started funding a network of what it calls Centers for Children’s Environmental Health and Disease Prevention Research. There is one at Mount Sinai and another at Harvard (the respective homes of Landrigan and Grandjean), and there are others at Columbia, UC Berkeley, and elsewhere.

Those centers have established strong research programs called prospective birth-cohort studies. Scientists enroll pregnant female subjects and carefully record objective measures of environmental exposure, using things like blood samples, urine samples, and maybe even dust and air samples from their homes. After the babies are born, the researchers follow up with them at various points in their childhoods. These studies are expensive and take a long time, but they’re incomparably good at connecting prenatal exposures with lost IQ points, shortened attention span, or emergence of ADHD.

Functional MRI reveals the effect of prenatal methylmercury exposure
in three adolescents. Subjectes were asked to tap the fingers of their left hands.
In the control group (row B), only the right side of the brain was activated.
In the subjects who had been exposed to methylmercury (row A),
an abnormal activation pattern shows that both sides are involved.
(The Lancet Neurology)

“That’s the big breakthrough,” Landrigan says. "The scientific community has mastered the technique of doing these studies, and they’ve been running long enough that they’re beginning to put out some spectacularly good results.”

At Columbia, for instance, the children’s center is investigating whether children exposed in the womb to BPA and polycyclic aromatic hydrocarbons (PAHs)—byproducts from burning fossil fuels—are more likely to develop learning and behavior disorders than children not exposed. They have also shown that high prenatal exposure to air pollutants like PAHs are associated with attention problems, anxiety, and depression at ages 5 to 7 years. It was this center, together with the UC Berkeley and Mount Sinai children’s centers, that first identified the detrimental impact of chlorpyrifos on IQ and brain development.

The researchers even used MRI testing to show that these chemicals appear to change children’s brain structure, causing thinning of the cortex. Other children’s centers are looking at the extent to which these and other chemicals—including arsenic from well water, brominated flame retardants, and the anti-corrosion agent manganese—are to blame for a range of possible neurologic disorders.

Impressive as all this research investment is, the larger question remains: Why are we looking at these hazards now—instead of before we introduced these chemicals into the world?

The Insidious Rise of Lead

The problem with toxic substances is that their effects can be insidious. Take the example of lead—a chemical that lingered in gasoline, house paints, and children's toys for decades before scientists realized the true extent of the damage.

Several years ago, a four-year-old boy in Oregon began complaining of stomach pain and vomiting. Doctors reassured his parents that it was likely a viral illness, but his symptoms worsened, and he became completely unable to eat. He also had a badly swollen cheek. The doctors determined that the boy had bitten himself, so severely that it must have been during a seizure. Blood tests showed that he was anemic, and subsequent tests found that he had extremely high levels of lead (123 micrograms per deciliter of blood).

The doctors began treating the boy with medication to help clear the lead. They also set out to find out where the lead was coming from. An investigation of the boy’s home, which was built in the 1990s, found no lead paint. Despite treatment, though, the boy’s lead tests remained abnormally high. So the doctors did an x-ray.

Inside the boy’s stomach was a one-inch metal medallion, which appeared bright white on the x-ray image. His parents recognized it as a toy necklace they had purchased from a vending machine approximately three weeks earlier. The state environmental quality lab later found that the medallion contained 38.8 percent lead. The manufacturer later did a voluntary recall of 1.4 million of the metal toy necklaces.

A late 19th-century advertisement for lead paint (Boston Public Library)

By that time, manufacturers had been using the toxic substance for centuries, despite clearly dangerous effects. In 1786, Benjamin Franklin wrote to a friend about the first time he heard of lead poisoning. When he was a boy, he recounted, there had been “a complaint from North Carolina against New England Rum, that it poisoned their people, giving them the dry bellyache, with a loss of the use of their limbs. The distilleries being examined on the occasion, it was found that several of them used leaden still-heads and worms, and the physicians were of the opinion that the mischief was occasioned by that use of lead.” Franklin went on to describe his observations of similar symptoms in patients at a Paris hospital. When he inquired about their occupations, he discovered that these men were plumbers, glaziers, and painters.

In 1921, General Motors began adding tetraethyl lead to gasoline. Lead gave gasoline a higher octane rating, which meant it could handle more compression without combusting. In practical terms, that meant more powerful engines, faster warplanes, and better industrial transport. The Ethyl Corporation that produced leaded gasoline was a joint venture between GM, Standard Oil, and DuPont. One of its executives, Frank Howard, called leaded gasoline “an apparent gift of God,” even as the plant where tetraethyl lead was synthesized became known as “the Houses of Butterflies,” because it was not uncommon for workers to experience hallucinations of insects on their skin.

Americans in the 1950s and ’60s were still widely exposed to unregulated leaded gasoline and paint, as well as piping, batteries, cosmetics, ceramics, and glass. Around that time, studies began to reveal the widespread existence of “subclinical” lead poisoning—damage that was not severe enough to meet diagnostic criteria for a neurologic disease, but would prevent the child from ever achieving optimal intellectual functioning. By 1969, microbiologist and Pulitzer-Prize-winning writer René Dubos said that the problem of lead exposure was “so well-defined, so neatly packaged, with both causes and cures known, that if we don't eliminate this social crime, our society deserves all the disasters that have been forecast for it.”

Four-year-old Tanya Brinson is tested for lead paint poisoning
at Boston City Hall in June 1975. (Peter Bregg/AP)

By the mid 1970s, the average U.S. preschool child had 15 micrograms of lead per deciliter of blood. Eighty-eight percent of children had a level exceeding 10 μg/dL—which is twice what the CDC currently considers toxic. Among poor black children, the average level was markedly higher: 23 μg/dL.

Instead of making sweeping policy changes, experts largely accused low-income parents—especially mothers—of inadequate supervision and fostering pathological behaviors that led children to eat paint. With parental ineptitude to blame, and poor, minority children bearing the brunt of the problem, a systematic approach to eliminating lead was a low national priority. Bellinger recounted this in the Journal of Clinical Investigation, writing that children were essentially sentinels, used to identify the presence of lead hazards.

“As long as the ranks of the lead poisoned consisted primarily of the children of politically and economically disenfranchised parents,” he wrote, “it was hard to interest politicians in the problem. Little political capital could be accumulated by tackling the problem.”

Jackie Lay
Finally in 1975, the EPA required a gradual phasing of lead out of gasoline. Two years later, the Consumer Product Safety Commission said that residential paint could contain no more than 0.06 percent lead.

Meanwhile there is still disagreement as to what constitutes a safe level of lead exposure—and if there even is such a thing. As more and more evidence came out over the years showing that low levels are in fact toxic to developing brains, the CDC incrementally lowered that threshold—from 60 micrograms per deciliter of blood in 1970 to 40 in 1971, 30 in 1975, 25 in 1985, 10 in 1991, and finally to just five in 2012.

By 2009 the average lead concentration in the blood Americans was about 1.2 μg/dL for young children—just 8 percent what it was in 1980. Bellinger notes that even this relatively low level is still “substantially elevated from an evolutionary perspective”—many times higher than before our ancestors “began to disturb the natural distribution of lead in the earth's crust.”

“Are the blood lead levels of contemporary humans generally below the threshold of toxicity?” Bellinger wrote. “Let us hope so, but the conclusion that they are is based more on faith than on evidence.”

The Toothless Law and the New Test

It's surprising to learn how little evidence there is for the safety of chemicals all around us, in our walls and furniture, in our water and air. Many consumers assume there is a rigorous testing process before a new chemical is allowed to be a part of a consumer product. Or at least some process.

“We still don’t have any kind of decent law on the books that requires that chemicals be tested for safety before they come to market,” Landrigan said.

The law we do have is the Toxic Substances Control Act (TSCA, pronouncedtoss-ka among those in the know). Passed in 1976 under President Gerald Ford, it is still today the primary U.S. law regulating chemicals used in everyday products. On its face intended to protect people and the environment from dangerous chemical exposure, it is widely acknowledged to have fallen short of its magnanimous goal. It only requires testing for a small percentage of chemicals, those deemed an “unreasonable risk.”

“It’s just an obsolete, toothless, broken piece of legislation,” said Landrigan. “For example, in the early 1990s, EPA was unable to ban asbestos under TSCA.” This was after the National Toxicology Program had classified asbestos as a known cancer-causing agent, and the World Health Organization had called for a global ban. The EPA did briefly succeed in banning asbestos in the U.S. in 1989, but a court of appeals overturned the ban in 1991. Asbestos is still used in consumer products in the U.S., including building materials like shingles and pipe wrap, and auto parts like brake pads.

Landrigan also calls it “a particularly egregious lapse” that when TSCA was enacted, the 62,000 chemicals already on the market were grandfathered in, such that no toxicity testing was required of them. These chemicals were, as Landrigan puts it, “simply presumed safe” and allowed to remain in commerce until a substantial health concern came to public attention.

In the nearly 40 years since the law’s passage, more than 20,000 new chemicals have entered the market. “Only five have been removed,” Landrigan says. He notes that the CDC has picked up measurable levels of hundreds of these chemicals in the blood and urine of “virtually all Americans.” Yet, unlike food and drugs, they enter commerce largely untested.

Landrigan and Grandjean’s purpose in declaring a silent pandemic was less about the 12 named substances and more about using them as cautionary tales. They named in their list a few chemicals that still appear be imminent threats, but they also include some that have been highly restricted in their use for a long time. And at least one of them, fluoride, has proven beneficial in small doses.

“Fluoride is very much a two-edged sword,” Landrigan said. “There’s no question that, at low doses, it’s beneficial.” Flouride has been shown to prevent dental cavities and aid skeletal growth. At higher levels, though, it causes tooth and bone lesions. The epidemiologic studies cited by Grandjean and Landrigan, which came from China, imply that high fluoride exposure has negative effects on brain growth.

“Are the exposure levels in China comparable to what we have in our drinking water and toothpaste?” I asked.

“No, they’re probably higher,” Landrigan said. “In some places in China, there are naturally high levels of fluoride in the groundwater, which picks it up because it’s water-soluble.”

“So your advice isn’t to take it out of our toothpaste?”

“Not at all,” Landrigan said. “I think it’s very good to have in toothpaste.”

He’s more concerned about flame-retardants—a group of compounds known as polybrominated diphenyl ethers (PBDEs). These chemicals came into vogue after their predecessors, called PCBs (polychlorinated biphenyl ethers), were banned in 1979.

By the time it became clear that PCBs caused cancer—and a variety of other adverse health effects on the immune, reproductive, nervous, and endocrine systems—they’d been put into hundreds of industrial and commercial uses like plastics and rubber products. So manufacturers switched to PBDEs and advertised PCB-free products, assuming—or, at least, implying—that PBDEs wouldn’t cause problems of their own.

“California, at the urging of the chemical industry several years ago, put the highest standard in the world on the levels of PBDEs that needed to be included in them,” Landrigan explained. “The result is that people in California have the highest levels of brominated flame retardants in their bodies.”

The state finally banned PDBEs in 2006, after studies from Columbia showed high quantities of the compound in women’s breast milk and linked it to IQ losses and shortening of attention span. Between 2008 and 2012, PDBE levels in the blood of California residents decreased by two-thirds.

Landrigan and Grandjean argue that stronger chemical safety legislation could have made all of this back-peddling damage control unnecessary. They don’t expect every chemical to go through long-term, randomized control studies prior to its release. Rather, they want to see industrial chemicals screened through a simple cell-based test. If that test were to come out positive—if the cells in the petri dish showed any kind of toxic reaction—then the chemical would be tested further.

A next step from there might be an animal testing model. The drawbacks there, Grandjean told me, are that “those programs are expensive, they take time, you have to kill hundreds and thousands of mice and rats.” However, he adds, “if a company has developed a very useful substance, and it turns out to be toxic to nerve cells in petri dishes, then maybe animal testing is the next step.”

“I don’t think that that should necessarily be a requirement,” Grandjean said. “But I can see if a company has developed a very useful substance, and it turns out to be toxic to nerve cells in petri dishes, then maybe that is the next step.”

Landrigan and Grandjean both mentioned something they called Tox21, the Toxicology in the Twenty-First Century program program, which is laying groundwork for a new kind of accelerated, large-scale testing. “TSCA reform really falls under EPA’s jurisdiction,” Landrigan said. “At the NIH and National Institute of Environmental Health Sciences, though, that’s where the latest research on this is.”Jackie Lay

When I heard that this Tox21 program is teaching a very large yellow robot to do large-scale rapid chemical testing, I had to learn more. Dr. Linda Birnbaum is the director of the National Institute of Environmental Health Sciences and the National Toxicology Program in North Carolina’s Research Triangle. Birnbaum oversees federal funding for research to discover how the environment influences health and disease, including Tox21.

“If you want to do the full battery of current tests that we have on a chemical, you’re looking at least five years and about $5 million,” Birnbaum told me. “We’re not going to be able to do that on large numbers of chemicals.” The robot is being trained to scan thousands of chemicals at a time and recognize threats inexpensively and quickly—before people get sick. It’s also using alternative testing models—looking at not just isolated cells, but also simple organisms like the roundworm C. elegans or zebrafish—to answer certain basic questions.

The Tox21 robot screening system at the NIH Chemical Genomics Center in Rockville, Maryland. This robot is part of a program that is refining a process to test industrial chemicals for safety quickly and efficiently. It places chemicals on plates with more than 1,500 wells that contain different types of human or rodent cells. (NIH)

The program is also looking at how a single chemical might affect a wide range of people. “We’re looking at 1,000 different human genomes from nine different ethnic groups on five continents,” Birnbaum told me.

Like Landrigan, Birnbaum raised the specter of the tens of thousands of chemicals grandfathered in 1976 that underwent no testing, as well as the commonly cited data that less than 20 percent of the 80,000 chemicals in commerce have had any testing at all. She spoke wistfully of the European Union’s chemical testing protocol, a model Grandjean had told me was “very reasonable.”

It’s called REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals), and it involves a tiered approach to regulation: If a compound is produced in small amounts, only some cursory information is required. If greater amounts are produced or imported, the EU requires more in-depth testing, such as animal experiments and two-generation studies.

“We’ve learned a heck of a lot in the last 30 to 40 years about the safety of chemicals and what can cause problems,” Birnbaum said, “and it would be really nice if our regulations required us to use some of the newer science to answer the questions of safety.”

Don’t Panic?

“When you use the word pandemic, that’s a scare word,” said Laura Plunkett. “And that’s my problem. There’s a more responsible way to express it. I understand that they want to bring it to attention, but when you bring it to attention, you can still do it in what I would say is a scientifically defensible manner.”

Plunkett has a Ph.D. in pharmacology and toxicology. Reviewing articles written in the wake of the publicity around The Lancet Neurology paper, I was struck by the definitive title of her blog post on a site called Science 20: “There is No Pandemic of Chemicals Causing Brain Disorders in Children.” Plunkett has been a diplomat for the American Board of Toxicology since 1984. She taught for a while and did research at NIH, but she is now an independent consultant running her own company, Integrative Biostrategies.

One of her clients is the American Chemistry Council. She also has clients in the food, pesticide, and chemical business—“industry ties,” as they say. With that in mind, I sought her out as an established scientist who has worked on the side of the chemical-producing companies. Her blog post about the Lancet article was the only response I found telling people not to panic.

“What [Landrigan and Grandjean] are doing with the data is missing the key component, which is the dose,” Plunkett explained. “Many of the chemicals they talk about are well established to be neurodevelopmental toxicants in children—but it’s all about how much they’re exposed to. Just like anything else. If you don’t give people enough, or if you don’t take enough in your water or food or the air you breathe, you’re not going to have an effect.”

Plunkett insists that, unlike lead, some of the chemicals on the Lancet Neurology list are only developmental toxicants at very high levels—the sort, she says, “that nobody would be exposed to on a daily basis.”

Plunkett says she has no problem with a call to ensure that chemical testing is as thorough as possible. “But then to say, and by the way, if you look at the data, ‘We’ve been poisoning people for the last 10 years’? That’s a whole other step that isn’t supported by the data they point to.”

I asked her how concerned American parents should be about certain individual chemicals on Grandjean and Landrigan’s list. “I mean, we knew lead was a problem 30 years ago,” she said, “and that’s why we removed it from gasoline, and that’s why we don’t let it in solder and cans, and we’ve taken lead-based paint off the market.”

“If you really look at the data on fluoride,” she continued, “trying to link an IQ deficit in a population with that chemical is almost impossible to do. Even though statistically, randomly they may have found a relationship, that doesn’t prove anything—it identifies a hazard but doesn’t prove there’s a cause and effect between the two things.”

What about the chemical that most concerned Landrigan, the pesticide chlorpyrifos?

“No, because the organophosphate pesticides are one of the most highly regulated groups of chemicals that are out there. The EPA regulates those such that if they’re used in agriculture, people are exposed to very, very low levels.”

Pesticides are indeed more regulated than other industrial chemicals. Before manufacturers can sell pesticides in the U.S., the EPA must ensure that they meet federal standards to protect human health and the environment. Only then will the EPA grant a "registration" or license that permits a pesticide's distribution, sale, and use. The EPA also sets maximum levels for the residue that remains in or on foods once they’re sold.

An EPA spokesperson told me that a company introducing a new pesticide must “demonstrate more than 100 different scientific studies and tests from applicants.” The EPA also said that since 1996’s Food Quality Protection Act, it has added “an additional safety factor to account for developmental risks and incomplete data when considering a pesticide’s effect on infants and children, and any special sensitivity and exposure to pesticide chemicals that infants and children may have.”

Landrigan and Grandjean don’t believe that’s always sufficient; the dose may make the poison, but not everyone believes the EPA’s limits are right for everyone.

When I asked Plunkett whether new industrial chemicals were being screened rigorously enough, even she cited the need to strengthen the Toxic Substances Control Act of 1976. “I’m a very strong proponent of fixing the holes we have,” she said, “and we do have some holes under the old system, under TSCA, and those are what the new improvements are going to take care of. They’re going to allow us to look at the chemicals out there we don’t have a lot of data on—and really those are the ones I’m more concerned about.”

The High Price of Lost IQ

Everyone I spoke to for this story agreed that TSCA needs to be fixed. But every attempt has met with bitter opposition. All parties want it to happen; they just want it to happen on their own terms. Unless it does, they don’t want it to happen at all.

Last May, a bipartisan group of 22 senators, led by Frank Lautenberg and David Vitter, introducing the Chemical Safety Improvement Act of 2013. Lautenberg, then 89 years old, was the last surviving World War II veteran in the Senate and a longtime champion of environmental safety. (Among other things, he wrote the bill that banned smoking on commercial airlines.) A month after he introduced his TSCA reform bill, Lautenberg died of pneumonia.

After Lautenberg’s death, Senator Barbara Boxer told reporters the bill “would not have a chance” of passing without major changes. “I will be honest with you,” said Boxer, who chairs the Committee on Environment and Public Works, “this is the most opposition I’ve ever seen to any bill introduced in this committee.”

Some of the resistance came from environmental and health advocates who felt the bill would actually make it harder for states to regulate the chemicals that were grandfathered in by TSCA. Their fears intensified in January, after 10,000 gallons of a coal-processing substance poured into West Virginia’s Elk River, contaminating a nearby water treatment plant. (The Wall Street Journal reported, “Little is known about the chemical's long-term health effects on people, although it isn't believed to be highly toxic.”)

In February, with Lautenberg’s bill stalled in the Senate committee, Republican Representative John Shimkus seized the opportunity to introduce another reform option called the Chemicals in Commerce Act. The chemical industry applauded Shimkus’ bill—it won support from the American Chemistry Council, American Cleaning Institute, and the Society of Chemical Manufacturers and Affiliates.

Earlier this month at the GlobalChem conference in Baltimore, Dow Chemical’s Director of Products Sustainability and Compliance Connie Deford said that TCSA reform was in the interests of the chemical sector, acknowledging that consumer confidence in the industry is at an all-time low.

The EPA Responds

The agency says it has taken the following actions to reduce exposure to the chemicals mentioned in Grandjean and Landrigan's report:

  • Chlorpyrifos: Banned all uses in and around homes
  • Polybrominated diphenyl ethers: Reviewing all new uses, following a voluntary phase out by U.S. manufacturers
  • Lead: Numerous federal regulations over the past few decades, leading to dramatically reduced childhood blood lead levels
  • Methylmercury: Significant efforts to reduce exposure, including 2011 standards that reduce pollution from coal and oil-fired power plants
  • Polychlorinated biphenyls: TSCA banned the manufacture and import of PCBs, and EPA is reassessing the largest remaining uses
  • Arsenic: Banned some types of arsenic, restricted others
  • Fluoride: Established safe drinking water standards and currently considering other revisions
  • Toluene: Included in the 2012 Work Plan, with assessment to begin by 2017
  • Manganese: Included in the 2012 Work Plan, with assessment to begin by 2017
  • Tetrachloroethylene: Included in the 2012 Work Plan, with assessment to begin by 2017

Yet the Chemicals in Commerce Act has provoked strong criticism from groups like the Center for Environmental Health and the Natural Resources Defense Council. A senior scientist with the Environmental Defense Fund called the bill “even more onerous and paralyzing” than the present law, and Representative Henry Waxman, ranking member of the House Energy and Commerce Committee, said the bill “would weaken current law and endanger public health.”

I asked the EPA to comment on Landrigan and Grandjean’s claim that we are in the midst of a “silent pandemic” and inquired what, if anything, is being done about it. The agency responded by sending me a statement:

“EPA has taken action on a number of the chemicals highlighted in this report which have and are resulting in reduced exposures, better understanding, and more informed decisions.”

The agency included a list of the actions it has already taken to reduce exposure to the chemicals identified in the report. (See sidebar.) And it emphasized a 2012 “Work Plan,” which includes plans to assess more than 80 industrial chemicals in the coming years.

When I emailed the statement to Landrigan, he replied, “Many of the items that they list here are things that I helped to put in place.” (In 1997, he spent a sabbatical year setting up EPA’s Office of Children’s Health Protection.) He agreed that the EPA is doing a lot to protect children from environmental threats. “But the problem is that the good people within EPA are absolutely hamstrung by the lack of strong legislation,” he wrote.

“They can set up research centers to study chemicals and outreach and education programs, but without strong and enforceable chemical safety legislation, they cannot require industry to test new chemicals before they come to market, and they cannot do recalls of bad chemicals that are already on the market.”

Meanwhile, researchers like David Bellinger, who calculated IQ losses, are highlighting the financial cost to society of widespread cognitive decline. Economist Elise Gould has calculated that a loss of one IQ point corresponds to a loss of $17,815 in lifetime earnings. Based on that figure, she estimates that for the population that was six years old or younger in 2006, lead exposure will result in a total income loss of between $165 and $233 billion. The combined current levels of pesticides, mercury, and lead cause IQ losses amounting to around $120 billion annually—or about three percent of the annual budget of the U.S. government.

Low-income families are hit the hardest. No parent can avoid these toxins—they’re in our couches and in our air. They can’t be sweated out through hot yoga classes or cleansed with a juice fast. But to whatever extent these things can be avoided without better regulations, it costs money. Low-income parents might not have access to organic produce or be able to guarantee their children a low-lead household. When it comes to brain development, this puts low-income kids at even greater disadvantages—in their education, in their earnings, in their lifelong health and well-being.

Grandjean compares the problem to climate change. “We don’t have the luxury to sit back and wait until science figures out what’s really going on, what the mechanisms are, what the doses are, and that sort of thing. We’ve seen with lead and mercury and other poisons that it takes decades. And during that time we are essentially exposing the next generation to exactly the kind of chemicals that we want to protect them from.”


James Hamblin, M,D. is a senior editor at The Atlantic