When this study appeared last year, many media sources reported it as evidence that scientists had found “the ADHD gene”. There are two problems with this interpretation. Firstly, only a small proportion of patients carried “large rare” CNV. 85% did not carry any, although more detailed future studies, able to detect smaller CNVs, might have found more (the smaller they are, the harder they are to detect.)
The deeper problem is that there wasn’t just one CNV. In fact, there were dozens of different large deletions or duplications in the ADHD group. This is similar to the results of other CNV studies.
Furthermore, even when the same CNV turns up repeatedly in many independent patients, these patients very often have different diseases. Many of the leading risk CNVs for autism, say, have also been found in ADHD and schizophrenia, epilepsy, or intellectual disability – and vice versa.
To take just one example, the “15q13.3” deletion, so called because it affects a particular part of Chromosome 15, has been found in people with schizophrenia, epilepsy, autism, and possibly even antisocial behaviors.
So although scientists set out trying to discover the genetic causes of named psychiatric disorders like “autism” and “schizophrenia,” they’re increasingly finding that these diagnoses don’t correspond to particular genes at all.
Instead, it may be that these diagnostic categories are just describing particular symptoms of certain genetic disorders. So, rather than saying that 15q13.3 deletion causes schizophrenia, for example, in the future we might say that some of the features of schizophrenia are amongst the effects of the 15q13.3-deletion-syndrome.
It’s only early days yet, but as this research advances further, and as technology allows ever-smaller CNVs to be picked up, these kinds of genetic findings may present a serious challenge for existing psychiatric diagnostic systems.
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18 Comments
Add CommentI find this really interesting. From what I've read here, the approach sounds very similar to a voxel-based lesion symptom mapping (VLSM) protocol some labs are using with stroke populations. This has perked my interested enough to read a bit more. Thanks.
Reply | Report Abuse | Link to thisAnother point not mentioned here is that it is an open question as to whether SNPs or CNVs can truly account for the severe abnormalities often seen in these diseases. Note that even in the Nature paper cited in this article, the CNVs being analyzed were present in a fraction of a percent of the sample of patients diagnosed with schizophrenia. Similarly, while 15% of the ADHD sample in that Lancet paper might have the same CNV, 7% of controls did as well. Assuming a relatively high population rate of ADHD at say 5%, this would still mean that 10x more people without ADHD would have the variant than people with ADHD!
Reply | Report Abuse | Link to thisNow, admittedly it is not expected that individual gene variants will entirely account for these disorders--indeed, they are thought to arise from the interaction of multiple variants and environmental factors. But we will need to find a lot more variants if some of them are only associated with disease in <0.50% of the population. While it could be possible that there are thousands if not tens or hundreds of thousands of risk variants, which when combined in the right fashion with the right environment lead to a specific "disorders", this hypothesis is unproven. Unless we are missing out on a treasure trove of as yet undiscovered variants (perhaps we need better techniques?), we might need to consider looking a little deeper. Hence, a further question not directly explored by genetic analysis alone is whether abnormal down-stream regulation of gene and protein expression might play a role in these disorders, both during early development and adulthood. The real problem with this possibility is that its not exactly easy to analyze gene expression levels in the developing human brain.
But hey, only time will tell.
When Asperger's syndrome was recategorized as an Autism Spectrum Disorder, I think last year, I knew it was only a matter of time before my highly functional and gifted grandson would be classified by association with the mentally ill. Great job, SA...
Reply | Report Abuse | Link to this@jtwyder;
Reply | Report Abuse | Link to thisI am asperger's as well. However it is only considered a negative to be associated with the mentally ill because of the social stigma attached to mental illness, even though it is not a personal fault.
Have you questioned why society has such a stigma toward mental illness? Perhaps some critical thinking is in order.
I suspect that I have Asperger's as well, but when I was young children weren't subjected to psychological diagnostic analyses unless they were effectively dysfunctional.
Reply | Report Abuse | Link to thisI think that my grandson currently benefits from the additional assistance he receives as a result of his diagnosis, but risks being considered disabled and counterproductive in the near future by an overpopulated bureaucratic society struggling to administer inadequate resources.
I have also had experience in my many years with some who are mentally ill, dysfunctional and incompetent. Their ability to productively contribute to society is to varying degree limited and must be supported to some extent.
In my experience, social administrators tend be unable to make fine distinctions - do not allow your human rights to be violated by any administration of any public policy.
I suffer from a mental illness, chronic depression, so by some people's definition I am "crazy." but then I hear people arguing that we can have all the government services and benefits we want without having to pay for them, and that there is an infinite supply of fossil fuels which we can burn freely with no environmental problems. I think, ok I am crazy, but what is their excuse?
Reply | Report Abuse | Link to thisAnother kind of DNA, 'transport DNA', accounts for many 'disorders'. Find details in my essay 'The chip in the brain' at FQXi, and on my web site at www.scienceuncoiled.co.uk.
Reply | Report Abuse | Link to thisBy providing the right trace elements, many mental and physical illnesses can be prevented. Some are treatable with other elements, such as lithium substituting iodine in 'bipolar disorder'. For others, like Alzheimer's Disease, environmental factors such as air pollution play a key role.
A balanced mind comes with a balanced diet.
As for ADD or ADHD, could it be that it is an evolutionary plus until modern times? That is to say, it is a survival technique to be able to pay attention to everything around you if you're an explorer. You're more likely to pay attention to a crouching tiger or leaping dragon. Thus, the % difference of CNVs between ADHD and "normal" may be an effect and not a cause of something else and tht the difference CNV may be an evolutionary plus. Just a supposition. I'm not completely secure with evoutionary explanations of psychological "phenomena."
Reply | Report Abuse | Link to this"In my experience, social administrators tend be unable to make fine distinctions"
Reply | Report Abuse | Link to thisi think you unfairly cast aspersions on the mentally ill and your position is "anti-humanist" to put it mildly
first of all mentally ill people span a very broad spectrum of different illnesses and severities
before i even get into that, let me say that your horror at your grandson being lumped with the "mentally ill" is in itself horrifying to me
why? because it is exactly that sort of thinking, that sort of devaluation of life in those that have a mental illness that in the past led to things like the nazi program t4
they would have gassed you and your grandson too
i don't think the nazis were too concerned with fine distinctions
you may argue well, fine distinctions are obviously necessary! oh really? but,to what end? to filter those "deserving of life" from those who are not? pretty anti-humanistic imo
getting back to my first point, the mentally ill are often quite productive, and many can be found in the literary arts, performing arts, and visual arts, and even a rigorous, logical field like science
there are countless examples of mentally ill persons making massive contributions to human knowledge and culture, contributions that many "normals" could not even begin to approach
just to pick two off the top of my head:
Lord Byron
Ludwig Boltzman
i'm quite sure you've heard of them. would you be horrified to have your garndson lumped in with THEM?
i think we should be REALLY concerned with people who have very dangerous anti-social defects, those are the people that not only cost society vast sums in terms of court costs, law enforcment costs, and prison costs, among many others, but who also exact a very high cost on their victims and their families
the VAST majority of mentally ill persons hurt no one, sure there is the ocassional psychotic person, perhaps schizophrenic or bipolar manic, that in the midst of hallucinations unfortunately harms someone, but this is NOT TYPICAL and FAR different from the narcissist , borderline, or psychopath that actively hunts and hurts people, for the thrill of it
THAT'S where the "fine distinctions" should be made and those are the people that need to be treated in any way possible, from birth, to protect society, to protect the innocent
you've cast your net far too wide
The gigantic hole in this kind of chit-chat is that "mental illness" is defined by practitioners whose judgment is wholly subjective and involves seeing-what-they-expect-to-see.
Reply | Report Abuse | Link to thisSince they categorize and label people in ways that rarely have any objective validity it is hardly amazing that they can find no evidence to explain what they think they see.
Iam very doubtful about gene theory.If everything happen because of gene if we remove that gene from body can we will be happy?Gene theory is speculation we know very little information on gene till scientist eagerly applied it all disease.Scientist think they got lamp of Alibaba if that touch to any disease all is well. People will live healthy life forever.Are scientist living in fool paradise?
Reply | Report Abuse | Link to thisSo, many of these "mental illnesses" may be the brains attempt to cope with genetic variations. Two different brains may opt for two different strategies in dealing with the same genetic "mistake" because two different brains also have many other variations that are not identified as "defects". Perhaps that is how the same genetic variation generates different syndromes, or disorders.
Reply | Report Abuse | Link to thisThat makes treatment of these syndromes more complicated and individual. So different strategies will have success with different individuals. This is something which seems to be born out in experience.
Copy number variations are implicated in extremely serious and slow onset neurological dysfunctions, such as Huntington's Disease, to name but one.
Reply | Report Abuse | Link to thisSince schizophrenia is often correlated with neural damage or degeneration in a certain brain area, with onset occurring in adolescence or later, with a peak, CNV certainly likely as a major factor.
The rest of this note is on deteriorating commentary following this and other SA articles:
Commentary following SA articles should not degenerate into rant over imagined failure by authors to empathise with sufferers from cognitive or behavioral symptoms.
Whether journalist or scientist, the intent is humanitarian.
Mental disorders are clearly defined by protocol in professional intervention. The trait or symptoms must cause distress. There is a strong code of ethics adhered to by professional therapists, psychologists, and psychiatrists.
Commentators who are unaware of this may discover that their attacks are unfounded. Self-medication is unwise, as psychiatric medications are intended to reduce the cognitions and behaviors which cause patients and loved ones to experience significant distress.
Many medications are intended only as jump-starts helping sufferers return to healthy cognition. Our thoughts, beliefs, and actual neurological processes can sometimes be habitual; combined therapies are necessary to restore clients and patients to what they themselves regard as healthier, happier lives.
While many societies and governments over the world have attempted to define mental health, modern nations such as your own, have quite strong and active health providers who continually question and seek to safeguard our individual rights and health, resisting infringement of ethical bounds by government, vigorously supporting the rights of those who vary from mere social norm.
An extreme minority of sufferers of particular disorders can be a danger to others. Schizophrenia can be controlled, as can Bipolar I. Some sufferers are a danger to themselves without intervention.
These sufferers are not abused as they once were, in the more restrictive past.
An issue that commentors might consider is comorbidity. I have mentioned self-medication. Many popular drugs are key in pushing problem behavior over the bounds of safety and law. Yet many individuals abuse these neuroaffective chemicals, whether they have persistent and pervasive distressing feelings or not. A right to behave in dangerous ways is not automatically granted within any culture, however libertarian the leaning of advocates.
You show a distinct lack of reading comprehension. JT didn't cast aspersions on the mentally ill. He specifically cast aspersions on social administrators. Fine distinctions are needed to respond to each individual in an appropriate manner. Bureaucratic officials tend to boilerplate and not respond to individuals. I saw nothing in JTs post that was anti-humanistic in any way. Your lumping everyone together despite different needs is very remnicient of the Stalinist and Maoist death camp mind set. I find you to be somewhat anti-humanistic. Not that I think that is a bad thing. The so called humanists tend to do just as much harm as anyone else.
Reply | Report Abuse | Link to thisI have come to a conclusion that retardation and Autism are just part of a spectrum that has nothing to do with the mind or mental ability but rather is entirely about the memory.
Reply | Report Abuse | Link to thisIn autisms its often all about over attention and under attention and results thereof. Yet attention with results demands memory.
Likewise in retarded people its common for them to have great abilities at memory. This being because the interuption of memory is the cause of their retardation.
I'm confident there has been a great error in seeing these things as brain malfunctions when it was instead memory malfunctions.
Memory has not been understood for its primary role in learning and moving about.
I know that you were trying to condense your thoughts so as to avoid prolixity, but read the following sentence, and consider its probable first glance interpretation:
Reply | Report Abuse | Link to this''Your lumping everyone together despite different needs is very remnicient of the Stalinist and Maoist death camp mind.''
You say I have a lapse in reading comprehension, I say you have an unrealized talent and a celebrated career waiting for you in comedy writing.
If you need me to spell out the hilarious implications of your statement (well, at least I know with absolute certainty that you DO need me to spell "reminiscent" for you):
your statement strongly implies the following curious, and logically absurd ideas:
-lumping together people with different needs is one of the hallmarks of the Stalinist and Maoist death camp mind (presumably their ghastliest trait was throwing everybody, no matter who they were, into the same big death camp)
and furthermore...
-what is reprehensible about the Stalinist/Maoist mass slaughter mindset is that it is indiscriminate. It could be cured of this defect if it were differentiating, distinctive and personal.
(insert laugh track)
Surely you didn't mean that they needed lots of little death camps instead of just one big one?
Obviously what you meant to express is that you think I'm a proponent of Left Wing ideology and you wanted to point out where LWI leads, as if nobody had heard yet.
I find it curious that a mention of Nazism results in a knee jerk assumption that I am a proponent of Stalinist or Maoist Communism. Well, I suppose the knee jerks both ways then...ARE YOU A NAZI?? No, I don't think so. But look at the ridiculous road you led us down (but it IS good for your comedy career).
In reality I was responding to the obvious (obvious if you can read not only words but what's between the lines) anti-mentally ill stance in the article. My examples were for illustration and for provoking discussion. Well, I suppose it worked, in a sort of way.
Bravo!
Reply | Report Abuse | Link to thisWho is controlling the control groups?
Your premise has the fault of not allowing for the nature of CNV's - unique to individuals. And thereby would not be found in higher percentages of people.
Reply | Report Abuse | Link to this