Younger children in a grade are more likely to be diagnosed with ADHD

AHDH immaturity - Copy.jpgA few weeks ago I was drawing attention to the fact that some children diagnosed with ADHD do not have attention deficits. Instead, a natural propensity for seeking more stimulation may have led to overdiagnosing and overmedicating these kids.

Another reason for the dramatic increase in ADHD diagnosis over the past couple of decades may stem in the increasingly age-inappropriate demands that we place on children. Namely, children in the same grade can be as much as 1 year apart in chronological age, but at these young ages 1 year means quite a lot in terms of cognitive and behavioral development. So if we put a standard of expectations based on how the older children behave, then the younger children in the same grade would fall short of these standards simply because they are too immature to live up to them.

So what does the data say? Two studies, Morrow et al. (2012) and Chen et al. (2016) checked to see if the younger children in a given grade are more likely to be diagnosed with ADHD and/or medicated. The first study was conducted in almost 1 million Canadian children, aged 6-12 years and the second investigated almost 400,000 Taiwanese children, aged 4-17 years.

In Canada, the cut-off for starting school in Dec. 31. Which means that in the first grade, a child born in January is almost a year older that a child born in December. Morrow et al. (2012) concluded that the children born in December were significantly more likely to receive a diagnosis of ADHD than those born in January (30% more likely for boys and 70% for girls). Moreover, the children born in December were more likely to be given an ADHD medication prescription (41% more likely for boys and 77% for girls).

In Taiwan, the cut-off date for starting school in August 31. Similar to the Canadian study, Chen et al. (2016) found that the children born in August were more likely to be diagnosed with ADHD and receive ADHD medication than the children born in September.

Now let’s be clear on one thing: ADHD is no trivial matter. It is a real disorder. It’s an incredibly debilitating disease for both children and their parents. Impulsivity, inattention and hyperactivity are the hallmarks of almost every activity the child engages in, leading to very poor school performance (the majority cannot get a college degree) and hard family life, plus a lifetime of stigma that brings its own “gifts” such as marginalization, loneliness, depression, anxiety, poor eating habits, etc.

The data presented above favors the “immaturity hypothesis” which posits that the behaviors expected out of some children cannot be performed not because something is wrong with them, but because they are simply too immature to be able to perform those behaviors. That does not mean that every child diagnosed with ADHD will just grow out of it; the researchers just point to the fact that ignoring the chronological age of the child coupled with prematurely entering a highly stressful and demanding system as school might lead to ADHD overdiagnosis.

Bottom line: ignoring the chronological age of the child might explain some of increase in prevalence of ADHD by overdiagnostication (in US alone, the rise is from 6% of children diagnosed with ADHD in 2000 to 11-15% in 2015).


  1. Morrow RL, Garland EJ, Wright JM, Maclure M, Taylor S, & Dormuth CR. (17 Apr 2012, Epub 5 Mar 2012). Influence of relative age on diagnosis and treatment of attention-deficit/hyperactivity disorder in children. Canadian Medical Association Journal, 184 (7), 755-762, doi: 10.1503/cmaj.111619. Article | FREE PDF 
  1. Chen M-H, Lan W-H, Bai Y-M, Huang K-L, Su T-P, Tsai S-J, Li C-T, Lin W-C, Chang W-H, & Pan T-L, Chen T-J, & Hsu J-W. (10 Mar 2016). Influence of Relative Age on Diagnosis and Treatment of Attention-Deficit Hyperactivity Disorder in Taiwanese Children. The Journal of Pediatrics [Epub ahead print]. DOI: Article | FREE PDF

By Neuronicus, 14 March 2016


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

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