Not all children diagnosed with ADHD have attention deficits


Given the alarming increase in the diagnosis of attention deficit/hyperactivity disorder (ADHD) over the last 20 years, I thought pertinent to feature today an older paper, from the year 2000.

Dopamine, one of the chemicals that the neurons use to communicate, has been heavily implicated in ADHD. So heavily in fact that Ritalin, the main drug used for the treatment of ADHD, has its main effects by boosting the amount of dopamine in the brain.

Swanson et al. (2000) reasoned that people with a particular genetic abnormality that makes their dopamine receptors work less optimally may have more chances to have ADHD. The specialist reader may want to know that the genetic abnormality in question refers to a 7-repeat allele of a 48-bp variable number of tandem repeats in exon 3 of the dopamine receptor number 4 located on chromosome 11, whose expression results in a weaker dopamine receptor. We’ll call it DRD4,7-present as opposed to DRD4,7-absent (i.e. people without this genetic abnormality).

They had access to 96 children diagnosed with ADHD after the diagnostic criteria of DSM-IV and 48 matched controls (children of the same gender, age, school affiliation, socio-economic status etc. but without ADHD). About half of the children diagnosed with ADHD had the DRD4,7-present.

The authors tested the children on 3 tasks:

(i) a color-word task to probe the executive function network linked to anterior cingulate brain regions and to conflict resolution;
(ii) a cued-detection task to probe the orienting and alerting networks linked to posterior parietal and frontal brain regions and to shifting and maintenance of attention; and
(iii) a go-change task to probe the alerting network (and the ability to initiate a series of rapid response in a choice reaction time task), as well as the executive network (and the ability to inhibit a response and re-engage to make another response) (p. 4756).

Invalidating the authors’ hypothesis, the results showed that the controls and the DRD4,7-present had similar performance at these tasks, in contrast to the DRD4,7-absent who showed “clear abnormalities in performance on these neuropsychological tests of attention” (p. 4757).

This means two things:
1) Half of the children diagnosed with ADHD did not have an attention deficit.
2) These same children had the DRD4,7-present genetic abnormality, which has been previously linked with novelty seeking and risky behaviors. So it may be just possible that these children do not suffer from ADHD, but “may be easily bored in the absence of highly stimulating conditions, may show delay aversion and choose to avoid waiting, may have a style difference that is adaptive in some situations, and may benefit from high activity levels during childhood” (p. 4758).

Great paper and highly influential. The last author of the article (meaning the chief of the laboratory) is none other that Michael I. Posner, whose attentional networks, models, and tests feature every psychology and neuroscience textbook. If he doesn’t know about attention, then I don’t know who is.

One of the reasons I chose this paper is because it seems to me that a lot of teachers, nurses, social workers, or even pediatricians feel qualified to scare the living life out of parents by suggesting that their unruly child may have ADHD. In deference to most form the above-mentioned professions, the majority of people recognize their limits and tell the concerned parents to have the child tested by a qualified psychologist. And, unfortunately, even that may result in dosing your child with Ritalin needlessly when the child’s propensity toward a sensation-seeking temperament and extravert personality, may instead require a different approach to learning with a higher level of stimulation (after all, the children form the above study had been diagnosed by qualified people using their latest diagnosis manual).

Bottom line: beware of any psychologist or psychiatrist who does not employ a battery of attention tests when diagnosing your child with ADHD.

Reference: Swanson J, Oosterlaan J, Murias M, Schuck S, Flodman P, Spence MA, Wasdell M, Ding Y, Chi HC, Smith M, Mann M, Carlson C, Kennedy JL, Sergeant JA, Leung P, Zhang YP, Sadeh A, Chen C, Whalen CK, Babb KA, Moyzis R, & Posner MI. (25 April 2000). Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proceedings of the National Academy of Sciences of the United States of America, 97(9):4754-4759. doi: 10.1073/pnas.080070897. Article | FREE PDF

P.S. If you think that “weeell, this research happened 16 years ago, surely something came out of it” then think again. The newer DSM-V’s criteria for diagnosis are likely to cause an increase in the prevalence of diagnosis of ADHD.

By Neuronicus, 26 February 2016


Pic of the day: Abundant vertebrate

most abundant vert - Copy

Fish Reference: Nelson, J. S. (2006). Fishes of the World. 4th ed. John Wiley & Sons, p. 209

Bird Reference: Strycker, N. (2014). The Thing with Feathers: The Surprising Lives of Birds and What They Reveal About Being Human. Riverhead Books

Autism cure by gene therapy

shank3 - Copy

Nothing short of an autism cure is promised by this hot new research paper.

Among many thousands of proteins that a neuron needs to make in order to function properly there is one called SHANK3 made from the gene shank3. (Note the customary writing: by consensus, a gene’s name is written using small caps and italicized, whereas the protein’s name that results from that gene expression is written with caps).

This protein is important for the correct assembly of synapses and previous work has shown that if you delete its gene in mice they show autistic-like behavior. Similarly, some people with autism, but by far not all, have a deletion on Chromosome 22, where the protein’s gene is located.

The straightforward approach would be to restore the protein production into the adult autistic mouse and see what happens. Well, one problem with that is keeping the concentration of the protein at the optimum level, because if the mouse makes too much of it, then the mouse develops ADHD and bipolar.

So the researchers developed a really neat genetic model in which they managed to turn on and off the shank3 gene at will by giving the mouse a drug called tamoxifen (don’t take this drug for autism! Beside the fact that is not going to work because you’re not a genetically engineered mouse with a Cre-dependent genetic switch on your shank3, it is also very toxic and used only in some form of cancers when is believed that the benefits outweigh the horrible side effects).

In young adult mice, the turning on of the gene resulted in normalization of synapses in the striatum, a brain region heavily involved in autistic behaviors. The synapses were comparable to normal synapses in some aspects (from the looks, i.e. postsynaptic density scaffolding, to the works, i.e. electrophysiological properties) and even more so in others (more dendritic spines than normal, meaning more synapses, presumably). This molecular repair has been mirrored by some behavioral rescue: although these mice still had more anxiety and more coordination problems than the control mice, their social aversion and repetitive behaviors disappeared. And the really really cool part of all this is that this reversal of autistic behaviors was done in ADULT mice.

Now, when the researchers turned the gene on in 20 days old mice (which is, roughly, the equivalent of the entering the toddling stage in humans), all four behaviors were rescued: social aversion, repetitive, coordination, and anxiety. Which tells us two things: first, the younger you intervene, the more improvements you get and, second and equally important, in adult, while some circuits seem to be irreversibly developed in a certain way, some other neural pathways are still plastic enough as to be amenable to change.

Awesome, awesome, awesome. Even if only a very small portion of people with autism have this genetic problem (about 1%), even if autism spectrum disorders encompass such a variety of behavioral abnormalities, this research may spark hope for a whole range of targeted gene therapies.

Reference: Mei Y, Monteiro P, Zhou Y, Kim JA, Gao X, Fu Z, Feng G. (Epub 17 Feb 2016). Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. Nature. doi: 10.1038/nature16971. Article | MIT press release

by Neuronicus, 19 February 2016


Astronomers discover new planet in OUR solar system

new planet - Copy

Did you grow up believing there are 9 planets in the solar system? And then felt robbed by the downgrading of Pluto?

Fear not, for there still may be hope to bring back the magic number 9! Last month, January 2016, a new report has emerged that claims to have evidence of the existence of a Neptune-sized planet that orbits our Sun every 15,000 years. Despite being as yet unseen, the suspect may be found well beyond Pluto and may have a staggering mass of ten Earths.

The researchers say that there is an infinitesimal chance for them to be wrong. And, according to their peers, the math in on their side. Basically, what they did was looking at the objects that exist after Neptune and orbit at a strange angle, out of the plane of the solar system. And their calculation say that only a planet that behaves this way (eccentric orbit, out of the plane, perihelion 180º away from the other objects perihelia) and is that heavy (more than 10 Earths) can explain the other objects’ orbits and clustering. Although, calculating probability of planetary existence based only on assumed gravitational effects has led to false conclusions before, just saying…

Now, the funny part: the chap that tries to bring back up to 9 the number of our planets is none other but THE SAME GUY who killed Pluto, by his infamous name, Mike “The Planet Slayer” Brown. More on the story here, in Science.

Reference: Batygin K & Brown ME (20 January 2016). Evidence for a distant giant planet in the solar system. The Astronomical Journal, 151(2): 1-12, doi:10.3847/0004-6256/151/2/22. Article | FREE PDF

By Neuronicus, 18 February 2016

A third way of neuronal communication

electrical fields - CopyEvery neuroscience or biology textbook will tell you that neurons communicate with one another in two ways: via chemical synapses (one neuron releases some substances that change the membrane potential of the receiving neuron) or via electrical synapses (neurons physically share some membrane proteins that allows the electrical impulse to go from one neuron to another). (Nota bene: for the taxonomic nitpickers, I decided that the other non-conventional forms of communication, like diffusion, fall in one or the other of the two categories above).

Now Qiu et al. (2015) have some evidence that there may be another way of neuronal chatting. Long ago (in 1924), Hans Berger observed that neurons have rhythmic and spontaneous electrical activity. The rhythmic activity of an entire population of neurons is called a wave and can be detected with rudimentary tools such as EEG. Qiu et al. reasoned that the speed of such a traveling wave is too slow to be explained by conventional neuronal communication (of which we know quite a lot).

So the researchers ran some computer simulations to test if diffuse electrical fields can explain the speed of a wave, instead of the conventional fast communications. In other words, can local, weak, slow endogenous fields sweep the brain by recruiting nearby neurons? The computer simulations said it is possible, with a very slow speed of 10 cm/s.

Then they recorded the electrical activity of mouse hippocampus isolated in a Petri dish. When the researchers blocked the electrical field there was a decrease in the speed of the wave, meaning the field is required for the wave speed observed.

To be fair, this is not a new idea; even in the early eighties these fields were suggested, because the wave persisted even when the other two ways of communicating have been blocked. And in the early noughts it was shown that a neural network is much more sensitive to electrical field manipulation than individual neurons. What makes this paper interesting is that the authors show that the endogenous electrical fields are not too weak to underlie the wave, as previously thought. The work has implications for the study of epilepsy, sleep, and memory.

Reference: Qiu C, Shivacharan RS, Zhang M, & Durand DM (2 December 2015). Can Neural Activity Propagate by Endogenous Electrical Field?, Journal of Neuroscience, 35(48): 15800-15811; doi: 10.1523/JNEUROSCI.1045-15.2015 Article | Full Text via Research Gate | ScienceAlert cover

By Neuronicus, 11 February 2016