An Uncomfortable Truth
Understanding the role of environmental toxins in autism and ADHD.
By Richard Deth
It’s enough to give any parent pause. Rates of autism and attention deficit hyperactivity disorder (ADHD) are rising fast—incredibly fast—increasing more than twentyfold over the last twenty years.
Genetic factors can’t account for a neurological “epidemic” like this, and it’s clear an exotic virus or bacterium isn’t to blame. This time, as cartoonist Walt Kelly once observed, “We have met the enemy, and he is us.”
According to mounting evidence, autism and ADHD numbers are being driven up by exposure to environmental toxins. The likely culprits: heavy metals and xenobiotics—manmade chemicals.
Today, working to stem this tidal wave of autism and ADHD cases, we’re making great strides in understanding how toxins can lead to brain disorders in humans, which is further yielding insights into the brain itself.
People who have a reduced capacity for attention, like those with autism and ADHD, have been shown to have less-synchronized brain activity. Step one in understanding autism and ADHD, therefore, is understanding the mechanisms that support brain synchrony.
When groups of nerve cells, or neurons, fire in synchrony, they combine to create a complex, unified network. When auditory neurons fire in synchrony with visual neurons, for instance, patterns of sound and light interact in the brain. Factor in the neuron activity from a memory circuit, created during a previous experience, and you start to see how a brain becomes a “mind” through the interaction of current and past experiences.
The brain creates attention by bringing selected information into synchrony. If the biochemical or metabolic events responsible for synchronizing neural networks fail for some reason, the brain won’t work as a unit—even if its individual regions continue to function quite well—and we lose the capacity for attention.
General anesthetics and other drugs that interrupt consciousness cause a loss of synchrony, especially synchrony in the so-called gamma frequency range. People with autism show impaired gamma synchrony. Conversely, gamma synchrony increases during attention and REM-sleep dreaming.
The neurotransmitter dopamine appears to increase gamma synchrony. Dopamine binds to receptor molecules on the surface of neurons. One such receptor, the D4 dopamine receptor (D4R), has been linked to both increased gamma synchrony at one extreme, and to the risk of ADHD at the other.
Ten years ago, my lab was the first to discover a unique biochemical activity of the D4R, known as methylation, which may be critical for promoting gamma synchrony during attention. We found that methylation is highly sensitive to a number of neurodevelopmental toxins, including heavy metals like lead and mercury. It’s also potently inhibited by alcohol.
Subsequently, we found these agents exert their effects by lowering levels of a cellular antioxidant. It turns out that most heavy metals and xenobiotics, including a number of common pesticides and herbicides, reduce the levels of this antioxidant in the body.
Lower-than-normal antioxidant levels lead to a condition known as oxidative stress. Recent studies of autistic children reveal they do indeed suffer from oxidative stress and a lower capacity for methylation. Together, these findings suggest environmental toxins are an important factor in causing autism.
To carry out methylation, the D4R needs a continuous supply of carbon atoms (methyl groups), which are carried by folic acid and transferred to the receptor by the vitamin B12-dependent enzyme known as methionine synthase. Methionine synthase also transfers folate-derived methyl groups to the sulfur amino acid homocysteine, whose levels are elevated in Alzheimer’s disease.
Studies have shown that treatment with methylB12, a form of vitamin B12, helps a significant proportion of autistic children. Clinical trials are currently under way to evaluate its utility in ADHD cases. This is not just a significant breakthrough for children who respond to methylB12. It’s an important clue in the hunt to determine which cellular processes cause autism.
My colleagues and I recently had the chance to evaluate methionine synthase status in brain samples from autistic subjects. We found the levels to be significantly lower than in age-matched controls. Other researchers have found evidence of oxidative stress in the same samples. The lower levels of methionine synthase we found may be an adaptive response as neurons struggle to synthesize more antioxidants.
When we analyzed methionine synthase in brain samples from elderly subjects, we were shocked to find that a segment of the enzyme was missing both in normal controls and in samples from individuals with Alzheimer’s disease. Loss of this segment increases antioxidant production, helping to offset the increase in oxidative stress that occurs with aging. Discoveries like these—as we study the disorders of the very young and the very old—tell us a lot about the brain in general.
Methylation activity is involved in more than 150 different metabolic pathways, exerting broad control over all cells in the body. Whenever methionine synthase is turned off by oxidative stress, each of these reactions slows.
This includes the ability of DNA methylation to affect gene expression, via a process known as epigenetic regulation.
Since all cells, starting with the fertilized egg, contain the same DNA, but only selected genes are expressed in a particular cell type, epigenetic regulation is clearly a big deal, especially during early development. When environmental toxins cause oxidative stress during these early years, the normal pattern of gene expression is altered, causing developmental delays that can last a lifetime.
Not everyone is equally sensitive to the effects of environmental toxins. Autistic children are more likely to show genetic variations associated with a higher sensitivity to oxidative stress and impaired methylation, which increase the chances for autism when toxin-exposure levels reach a critical threshold.
Boys are less resistant to oxidative stress than girls, in part because of the way testosterone inhibits the creation of antioxidants. It’s not surprising, then, that boys are four times more likely than girls to have autism and ADHD. (Environmental toxins tend to be particularly rough on males. When humans and other species are exposed to pollutants, the numbers of males decrease, reflecting a dip in the number of male births. In some species, these conditions give rise to females’ being able to reproduce without males.)
On the basis of these layers of scientific evidence, it seems pretty obvious that environmental factors pose a severe threat to humans’ neurocognitive abilities. So what should we do in response?
Well, we must first recognize the seriousness and immediacy of the problem. This is not a theoretical issue that may affect our grandchildren’s grandchildren. This has already affected a generation, and shows no sign of abating.
Then, as a society, we have to take on a challenging task: reducing potential sources of heavy-metal and xenobiotic exposure. This effort should be particularly directed at food and water supplies, lead-tainted toys, and flame retardants.
We must also act as individuals, by being vigilant about removing exposure sources present in our own homes.
And we must remember that there are clear health benefits to eating real food instead of manufactured food, organically grown food instead of products grown with pesticides and herbicides. If enough people make healthy choices, the food industry will make healthy products more available and affordable.
Ultimately, we have to build a higher level of awareness about the role of environmental toxins in autism and ADHD, not to mention the role of other manmade substances in such “epidemics” as obesity, diabetes, and asthma.
Once we recognize we really are our worst enemy, we’ll be quicker to call a truce, and start to create a cleaner, safer world for ourselves and our children.
Richard Deth is a professor
of pharmaceutical sciences in
Bouvé. Solving societal
challenges through research is a
linchpin of Northeastern’s
Academic Initiative.