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?

autism spectrum disorders and dsm-v politics

An article in the New York Times this morning by Simon Baron-Cohen addressed the debate in the DSM committee over subsuming the conditions of Autism and Aspergers in the fifth edition of the "psychiatric bible"(promised in 2012).  The committee is deliberating whether or not to eliminate Asperger from the diagnostic manual and characterize its discrete symptoms as a degree of autism in the spectrum (perhaps "intermediate functioning autism").

Autism and Asperger syndrome are both characterized by impaired communication skills, a desire for keenly focused stimuli and strong inclination toward repetition. They are distinguished only by a slower onset of language skills and latency of intelligence in autism, says Baron-Cohen.  He further suggests that this distinction is proving not to be concrete enough, and that the DSM-V committee's struggle with the controversy can be attributed to the lack of physiological distinction of these psychiatric conditions.

I would agree with Baron-Cohen that there is not currently enough genetic distinction between autism and Asperger syndrome to warrant their being entirely separate conditions outside the spectrum disorders umbrella in the DSM-V.  However, I think that defining Asperger syndrome idiosyncratically is important to preserve in the new manual.  Here is why:   

1)  Baron-Cohen mentions his own group's recent identification of 14 Asperger-specific genes,19 genes specific to autism and 7 shared (Chakrabarti et al 2009).  They measured 68 candidate genes in two experiments: the first measured autistic traits in an undiagnosed sample population using the Autism Spectrum Quotient; the second, using the Empathy Quotient.  These two experiments were designed to identify autistic and Asperger cases among the sample:

"We searched for common genetic variants (single nucleotide polymorphisms (SNPs)) on the assumption that autistic traits are continuously distributed in the general population [Constantino & Todd, 2005; Sung et al., 2005]."

"In Experiment 1, autistic traits (measured on AQ and/or EQ) were nominally associated at P<0.05 with SNPs from 19 genes. In Experiment 2, SNPs from 14 genes were nominally associated at P<0.05 with AS."

Six genes were nominally significant in both experiments. This study alone suggests that Asperger syndrome deserves a distinction as a sub-group in the Autism Spectrum Disorders (ASD) category that the DSM-V committee is considering, as opposed to eliminating it entirely, as is also being considered.

The Charkrabarti study is impressive, and the first step in the important attempt to identify the genetic and epigenetic correlates of autism and Asperger separately.  However, there is still an extensive amount of correlative research to be done.  A good amount of this is ongoing through the AutDB Project.

2)  If for no other reason than to preserve the honor of the venerable Hans Asperger.

3)  To keep company the solitary other recognized ASD, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS).*  Perhaps these could both become sub-groups in the ASD category.

It is noteworthy that a great deal of genetic research already refer to their studies as ASD interactions/links/correlations (PubMed or Google Scholar this).  I am terribly eager to find out whether or not this plays a strong role in the decision of the DSM-V committee.


*High- and Low-functioning autism are not classified as spectrum disorder subgroups, although they should be... and perhaps, one day, will be, provided there is a physiological distinction to be drawn between them, Asperger and PDD-NOS.

piaget + bohm

When we are infantile, we perceive the world in terms of transformations and continuity. When someone's head disappears behind the playpen wall, it no longer exists. And when someone's arms extend from behind a tree trunk, they are part of that tree trunk. And when that tree appears fairy-sized beside our hand, it is not because the tree is far away, but because you have discovered its untouchable miniature right in our presence. A thing happens to us between this time and adulthood that morphs that cononical perception into an interspersed mass of objects and interactions. Language.

Particularly Indo-European languages (English, French, German, etc.) are primarily based on nouns. We think, communicate and perceive based on what language has done to our interaction with the world. We fragment its natural cohesion just by the way we behold it.

Language was once verb-based... transformation-based. Native American languages, Bengali and other endangered linguistics. These were also peoples who interacted with reality as if it were all actualized in the same condition, and from the same piece of cloth and ultimately still cohesive.

empty thoughts VI

6. Hare and Tomasello (1998) speak to the differences between the way wolves and dogs respond to human gaze cues. Previous studies suggest that the ability of dogs to respond to the gaze of humans is a derivative of their ancestral skill of reading behavior of fellow hunters. Contrarily, wolves, even when reared by humans don’t exhibit such skill. The domesticated dog line has been evolving for thousands of years. It is, of yet, not conclusive as to when dog domestication began. Mitochondrial DNA says the wolf and dog lines split around 100,000 years ago. It is my perspective on this issue that for the wolf and dog genetic lines to split, there had to have been a large era of domestication that occurred first. Historical perspective entices me to infer that dogs are more evolutionarily equipped to respond to a human gaze cue than a wolf, who is more equipped to respond to peer gaze cues or hunting posture. I suppose my reaction, then, to H & T’s reference is that I don’t feel that it portrays anything novel to contribute to their article. Of course wolves don’t respond as well as dogs to the gaze cues of humans; being reared by humans does not replace thousands of years of species domestication and divergence. During their process of domestication, the skill of recognizing peer behavioral cues must have evolved to respond more directly to human (master) cues. I'm bored with their thoughts...

empty thoughts V

as i sit here in class wishing that Miller would become as awesome a professor as he is a person, but accepting that, tragically, this will never be...

5. Oh Steven Pinker, how I treasure you...

Pinker thinks grammar development is a support for non-selectionist theories of language development. He says that grammar is more complicated than it need be for the purposes of hunter gatherer lifestyle, with which I agree. However, I also think that when grammar/language was in initial stages of evolutionary development, it was probably exactly as complicated as it need be for that purpose. I like to think of the late H. s. sapiens as still being hunter-gatherers, and that as our hunting skills evolved to become more complicated, so did our language. This being said, I don’t think that the present complexity of language is an argument against the contribution of natural selection to language development. It’s just as conceivable an idea to me that just as our hunting skills suffer from a severe deficit inflicted by our obsession with making our lives easier and our physical selves more lazy, so has language diverged from being purely a survival tool into… well, Sheharazade on steroids. Then again, some of us have become so exotically lackadaisical with language that it's also become somewhat useless as a tool of any sort.

empty thoughts III

3. Fiona Scott and Simon Baron-Cohen conclude that the deficit in autism is due to an impairment of psychological reasoning, as opposed to logical or analogical reasoning. This seems to suggest a deficit in “mindblindness,” not Gestalt perception, as addressed by the article. Because mindblindness is defined by Baron-Cohen in another article as an inability to be aware of what is in another person’s mind, it becomes a separate issue from Gestalt perception entirely. The logical and analogical tests demonstrated that autistic children can reason with representations of representations, and identify relation between relations, which suggests that their perceptive grouping is intact, which is clearly not the case. I don’t get it.

The authors say that their evidence shows the deficit to be due to m-representation; the inability to represent and agent’s attitude toward something. They do not speak of which of their results support this, but continue to say that autism is more likely due to the child’s inability to represent mental states...metarepresentation? What is this jump they are making to conclude that this is an impairment of psychological reasoning? It makes more sense to me that an inability to represent mental states would reflect a deficit in analogical reasoning.

I would have appreciated a more direct response to their three main hypotheses. Speculating the three intelligence paradigms of logical, analogical and psychological reasoning were a strong approach to the question of whether autistic children are impaired selectively in psychological and not in non-social tasks. However, I think the importance of their conclusions was missed, and their discussion generally lacking, and did not address the relation of their various tests to their hypotheses... Neither do they definitively support or object to Cosmides’ theory which is the title of their paper. It seems that since Scott and Baron-Cohen concluded that social intelligence has evolved separately from non-social intelligence, they would discuss Cosmides’ theory that intelligence evolved to solve social problems.

so basically, my disappointment reflects that which I typically hold toward psychology papers... pity.