Contrary to those who claim that ADHD is a purely mental construct, the researchers found that ADHD patients had a markedly higher incidence of CNVs compared with controls: just over twice the amount on average but more than 5 times greater in those patients who were also diagnosed with intellectual disability. Furthermore, the CNVs in question resemble those already implicated in autism and schizophrenia. Indeed, the study identified specific genes shared by ADHD and these disorders, particularly on a stretch of chromosome 16 which contains a number of important genes already linked to schizophrenia, including one which interacts with DISC1 (for disrupted in schizophrenia #1).  

Both deletions and duplications were found in relation to genes inherited from both parents, and as I have pointed out in a previous post devoted to CNV, such variations in gene expression closely resemble genomic imprinting, in which one parent’s copy of a particular gene is expressed or silenced. Like CNV duplication, this can result in a doubling of a gene’s effect or in its negation, as in CNV deletion.

Such effects result in so-called sister disorders: independently described and seemingly unrelated syndromes whose symptoms are diametrically different and whose causes are opposite expression of the same or similar genes. The paradigm is Angelman and Prader-Willi syndromes: originally described independently, but now known to be both the result of opposite expression of a stretch of chromosome 15. Prader-Willi is the result of an imbalance in favour of the mother’s genes and produces a caricature of the ideal baby: a sleepy, undemanding child with a weak suck and cry and high pain threshold. Angelman (aka Happy Puppet Syndrome) is the opposite: a demanding, hyper-active, frequently suckling and crying child with a low pleasure threshold (“paroxysms of laughter” is one of the diagnostic criteria!).

All Prader-Willi patients with the version of the syndrome in which the entire chromosome 15 comes from the mother are diagnosed psychotic in adult life—the strongest case of genetic causation known to psychiatry—and Angelman children tend to be diagnosed autistic. However, Angelman children are also hyper-active, and Williams and co point out that their results “suggest that there could be a shared biological basis” to both autism and ADHD as many already suspect from the overlap of the symptoms.

However, the genetic overlap with schizophrenia and ADHD revealed by this study is more of a surprise and prompts me to repeat an observation I make at greater length in my book. This is that ADHD looks very much the diametric opposite of catatonic schizophrenia. In other words, we find hyper-activity in one case and frozen activity in the other; and as I illustrate in my book, where there is a deficit in attention in one there is hyper-attention to the point of paralysis in the other.

Finally, there is one last diametric contrast that fits the imprinted brain theory. This is the undeniable fact that while ADHD appears to be becoming more common, catatonia is now so rare that psychiatrists have been known to ask where all the catatonics have gone. If catatonia and ADHD are in fact sister syndromes, then we should not expect to find both if autism spectrum disorders are on the increase in the modern world. And even granted that some of that increase is the result of greater diagnostic sensitivity to ASD, the precipitous fall in catatonia suggests that there is a real underlying cause. Future studies extending Williams' and his colleagues’ marvellous finding will tell whether this is mere mentalizing on my part or a real mechanism which—like ADHD—is rooted in genetics and written into our DNA.