phthalates and ADHD

The outstanding debate on whether the benefits of soft plastics outweigh their potential harms continues. 

The group of esters called phthalates are used in an array of products ranging from pill capsules to children's toys to shower curtains.  A research group in Korea has found a strong positive correlation between ADHD behavioral characteristics and phthalate metabolites in the urine of Korean school children.  This is a particularly important study for two reasons: 1) a correlation between ADHD and phthalate exposure during critical periods of development has never been shown, and 2) the metabolite levels found in these children indicates the amount of exposure that can now be replicated in animal models.

"Previous animal studies (6,15,16) have shown that phthalate related metabolites induce hyperactivity in rats. These studies reported that pups treated with phthalate demonstrated 1.4 times the level of hyperactivity at night compared with control subjects. Such hyperactivity was dose-dependent, which is consistent with the results of our study."

"It is possible that the toxicity of phthalates is attributable to degeneration of dopaminergic neurons, leading to the hyperkinetics observed in rats in cases of 6-hydroxydopamine (OHDA) procedures (27). Well-known animal models of ADHD like the OHDA rat model suggest that the dopamine neuronal damage can provoke hyperactivity and impulsivity. Many structural magnetic resonance imaging studies showed striatal volume loss suggesting the dopamine neuronal loss in ADHD patients (28)."

"With DNA macroarray data, researchers have found that phthalate metabolites change
the expression patterns of various genes, including both the dopamine receptor D4 (DRD4) and the dopamine transporter in the midbrain (6). The dopamine receptor D4 and dopamine transporter gene expression modulation can induce changes in extracellular dopamine and neuronal dopamine sensitivity, resulting in hyperactivity and impulsivity in rats."

Here is something particularly interesting: if excessive exposure to phthalates is linked causally to ADHD phenotypes -- which has yet to be explored -- perhaps the time-release medications used to treat ADHD such as Wellbutrin and Ritalin should cease to use phthalates in the enteric coating of their medications.  It seems odd that they are so widely used in films of pharmaceutical capsules if for no other reason than their heavy reputation as endocrine disruptors.  Capsules can contain in the range of 3600 ug phthalates, while most studies estimate that the "safe" exposure range is near 20 ug per kilogram body weight.  That means the "safe" range for most young children is about 750 ug.  Note that phthalates do not bioaccumulate, so exposure levels are dailies.

"The bupropion (Wellbutrin® SR)  release rate has been improved by the introduction of two types of film coated active pellets that release the drug at different pH resulting in novel dissolution profiles. Inert spheres are initially coated with bupropion and hydroxypropyl methylcellulose. The active pellets containing bupropion comprise 70-75 weight % of the dosage form. An enteric coating, applied to about one third of the active drug pellets, is comprised of a film insoluble at low pH, such as hydroxypropyl methylcellulose phthalate. The second coating applied to the other two thirds of active drug pellets is comprised of a combination of a hydrophobic coating agent and methyl acrylic acid copolymer. The two pellet types are then combined in a capsule."

"The novel dosage forms are used to administer methylphenidate (Ritalin) in a pulsatile release manner... Suitable membrane coating materials for effecting delayed release include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, cellulose ester-ether phthalate, hydroxypropylcellulose phthalate, alkali salts of cellulose acetate phthalate, alkaline earth salts of cellulose acetate phthalate, hydroxypropylmethyl cellulose hexahydrophthalate, cellulose acetate hexahydrophthalate..."

on the stifling of creativity

An experiment was conducted by Desmond Morris in 1962 comparing the artistic creativity of young children and chimpanzees.  Remarkably, both chimp and human child became so engrossed in their painting that they showed very little interest in food, sex or other activities that would be expected to divert their interest.  The major revelation of this study was that creativity was, perhaps, a natural potential; yet, for many of us, the urge to create diminishes significantly as we grow older, revealing itself only in the sciences, music, art... and on a more modern note, advertising [trash].

A follow-up study to Morris' added a reward system to the chimps' sessions of abstract expressionism.  The results was that with each reward, the creativity and depth of the painints degenerated until producing only the minimal product necessary to obtain reward from the experimenter (The Biology of Art, Methuen London, 1962).

David Bohm has described this phenomenon as follows:

"In order to do something for a reward, the whole order of the activity, and the energy required for it, are determined by arbitrary requirements that are extraneous to the creative activity itself.  This activity then turns into soemthing mechanical and repititious, or else it mechanically seeks change for its own sake.  The state of intense passion and vibrant tension that goes with creative perception... then dies away.  The whole thing becomes boring and uninteresting so that the kind of energy needed for creative perception and action is lacking.  As a result, even greater rewards or punishments are needed to keep the activity going" (Science, order and creativity; 2000).

I've written about ADHD before, but was inspired to revisit the topic by a seminar forwarded to me:

http://www.ted.com/talks/lang/eng/ken_robinson_says_schools_kill_creativity.html

So my question is this: to what extent is the reward system of education -- any kind of education -- destructive to the development of the self?  Is not the self-consciousness, dissatisfaction and boredom resulting from intervention by directed creativity dangerous to development? Some of what were considered the greatest creative minds of history thwarted standardized education.  From the science realm alone (with which I am most familiar), Copernicus meandered through universities for seven years without bothering to fulfill a degree.  Da Vinci was educated by the royal Medici family, but education in the Italian Renaissance was its own matter entirely.  Tesla boycotted academia at the age of ten.  Thomas Edison never went. 

On the other hand, in more recent history it has become nearly impossible to achieve recognizable creativity without eons of academic vigor.  How is that demand defining the way we structure the reward system of education?  We pump in the sedatives to get this "most troubled" generation through the hoops.  In so doing, we are pummeling creativity from both ends: reward and sedation.  What will become of our next generation of scientists and artists?

ADHD News

Alright. I adore the Huffington Post. Truly. But this is the most ass-backwards half-written piece I think I've ever seen come out of there: ADHD Meds Abuse.

To paraphrase... "This non-profit study says this (kind of), but this big-pharma study says that (almost) - oh noes!... ... ..."

As a scientist, I take personal offense to this kind of writing. As a human being, I take umbrage to the lack of integrity in an article addressing an epidemic controversy such as ADHD. It's empty. There's not even an argument for or against the methodology of one study or another. There are no details as to how the study was conducted, no questioning the legitimacy of any of it, and the conclusion is that "the study lacks information on whether abusers were teens with ADHD, but anecdotal evidence suggests many are not."

... what? Really? Your conclusion is something that you left until the penultimate sentence to even bring up? And you're not going to expand on it? How the hell did Lindsay Tanner get the frontline with this thing? I'm almost more impressed with the public commentary... <shudders>

In effect, I think this article trammels the purpose of science writing, which is to translate primary literature into layman language. It is NOT to transliterate scientific discovery into utterances of empty and useless dribble. What is the purpose of this article? It can't possibly have had any other intent than to create hysteria, and that is the worst possible use of the media in general. First rule of translating: do not imply or directly suggest things that are completely irrelevant; please use intelligence.

I now firmly believe that if this Remicade business does not send me into remission and I am rejected from graduate school based on medical biases - yes, that is a legitimate possibility - I will have to go into science writing and do my utmost to revolutionize its currently upsetting condition.

ADHD

[disclaimer: incoherent thoughts brought on by benadryl and prednisone.. may or may not be refined at a later date]

this is my biff with amphetamines.

if the role of the 7R variation in the DRD4 allele is significant enough to be the primary candidate for insatiable novelty-seeking behavior characteristic of ADHD... why was Ritalin a good idea?

the idea is this. 7R variation in this particular dopamine receptor changes the metabotropic receptor's ability to control intracellular cAMP levels (cyclic adenosine monophosphate, which activates the membrane protein PKC (protein kinase C) releasing it from the membrane and allowing it to open potassium channels which then alter the electric potential of the cell which is what allows for DA release....for those who care). this means that cAMP is turned on constitutively, and as a result its cascade which eventually leads to the release of the cell's neurotransmitter (DA, in this case) is also kept running. so we've got the 7R mutation which is mostly responsible for overload of DA in several reward pathways. okay, so this addresses hyperactivity and abrupt and aberrant mood changes. why are we controlling this by introducing more amphetamine? this is not a neurotransmitter that is known to have a strong compensatory mechanism! introducing a consistent exogenous dose of amphetamine to try to control the amount of DA pumped into synapses does not work the same way as it does with steroids. your body takes longer to respond (namely, by reducing the amount of DA it is producing itself thereby reducing signal frequency)... and while it's trying to do so, the side effects of amphetamine take their toll. if the problem is the metabotropic DRD4 receptor, and the incessant activity of cAMP and its subsequent protein kinase cascade, altering DA levels exogenously is not going to cut it. right?

but here's my other objection. why do we need to cut it? why can't we accept it as a mutation and change our behavior to accommodate? step outside of the meme of conventional education and manipulate the outcome of this condition from the outside. this was, once upon a time, a beneficial characteristic, this insatiable novelty-seeking. can we look over our culture (particularly multi-nationally) and observe what its evolution has done to the minds of children and their capacity to explore? what were we meant to do if not explore? how does growth of any kind occur without exploration? how do we survive? okay enough with the annihilation of what are otherwise perfectly decent thoughts...