Genetic Mechanisms in ADHD

00:00 Introduction
01:01 Single genes
01:30 Two copies of a risk gene
01:48 Broken chromosomes
02:18 Extra chromosomes
02:56 Multiple gene variants
06:17 Inheritance vs. de novo mutations
10:39 Gene x environment interactions
11:24 gene x gene interactions
12:30 Epigenetics in ADHD
This video reviews the various potential genetic mechanisms that could be involved in ADHD, ruling some out while highlighting the promise of other mechanisms in accounting for ADHD, such as multiple gene variants and gene by environment interactions. I also discuss the newly emerging field of epigenetics in ADHD research, now in its infancy as highlighted in the review of research below.
C. Cecil & J. T. Nigg (2022). Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential. Molecular Diagnosis and Therapy, 26, 581-606.
link.springer.com/article/10....

[@WonkyGrub]

Just a small point of clarification, where you put the citation to the review is actually in the “video description” as it is called, generally the “thumbnail” of a video is the preview image people see before clicking on a video.

[@md82892]

In his book “Brain Energy” Chris Palmer says researchers couldn’t identify genes for a single mental disorder, all the genes identified are actually showing comorbidity with multiple mental disorders. So he says we can’t really say genes causing any specific mental disorder. His theory is, these genes are impacting the function of mitochondria in the nerve cells and when mitochondrial dysfunction happens it can cause multiple mental disorders. So according to him we can’t really talk about ADHD genes in this sense, the mechanism is more about mitochondria than ADHD (or any other comorbid disorders comes with it) He also explains why stimulant medications work, it’s not just fixing neurotransmitter imbalances, but also impacting mitochondrial dysfunction (hence improving symptoms) If this is true then we might have other remedies that improves mitochondrial function (such as sports, ketogenic diet, bacterial flora improvements etc) that may have better and more sustainable solution than stimulants. What would you take on this theory, it would be really interesting to hear a scientific rebuttal if you disagree.

[@russellbarkleyphd2023]

The work on mitochondrial DNA and its functions is really in its infancy in ADHD saying his saying this is more hypothetical than definitive right now. But it’s interesting. As for genes, yes the genes that are related to ADHD also overlap with some other disorders, like depression and ASD, but studies show that each disorder also has unique genetic contributions not shared by other disorders. So some genes predispose to a general risk for psychopathology while the addition of others to them seems to channel that risk into more specific disorders.

[@md82892]

@@russellbarkleyphd2023 thanks Prof. Barkley. He also provides extensive research on causes of mitochondria dysfunction in nerve cells and every single time this happens multiple different mental disorders becomes prevelant. With specific diet and lifestyle changes mitochondrial function can be improved, hence remission or complete symptom reduction is shown with treatment resistant mental disorders. If this is true, then wouldn’t ketogenic diet (which helps tremendously for schizophrenia, bipolar disorder or epilepsy) help for ADHD patients which share same or similar gene combinations? Surprisingly there isn’t much RCT’s done on ADHD with ketogenic diet, only some animal studies that shows promising results (but we can’t conclude the same for humans unless some researchers do these studies on humans) I asked Dr. Palmer on this but couldn’t get a reply, do you know any study that shows medical ketogenic diet helping ADHD patients?

[@jimwilliams3816]

I’m no expert, but it has long seemed to me that many behaviors which overlap multiple disorders could likely have similar physiological functions at their core, and quite possibly similar underlying genetic factors. If so, the hypothesis of common roots could apply whether or not mitochondria is the mechanism or not. My personal suspicion is that mitochondria could factor in, but I doubt any single mechanism is at the root of everything. That’s based on both my limited understanding of the complexities of genetic expression, and the multiple ways in which things can go wrong or at least be different, and a certain skepticism of any theory that purports to be too much of a deus ex machina. Still, I’m just a random guy on the Internet. Dr. Barkley knows far better than I.

[@annahunt3818]

My son and I were diagnosed with ADHD within the last year. I have also been on a keto diet for the past year. For the 2 months my son did it and when I stayed in ketosis during that time, I can’t say I noticed much difference. I will say that I love the diet and I have never been on or stuck with a diet for so long.. I feel much better overall when I’m on a clean keto diet. I’m even tempted to try the carnivore diet, but haven’t yet. I feel like it has benefitted me immensely, but I can’t speak to whether or not the keto diet has specifically benefitted my ADHD symptoms because I was also taking Vyvance during that time. I would absolutely be interested in more research as well!

[@ScienceisRadAF]

Wow! I wish I could explain the way the intro to this video made me feel. I’ll try. The very thought that a dr could verify my ADHD experience via genetics, and potentially even determine an ideal treatment, would be amazing. It would alleviate so much of the uncertainty and shame and vulnerability that I navigate. Having to go in every 3 months to renew my Rx feels an awful lot like going on trial every 90 days to prove my problem is real… it feels like at any point a doctor could just decide I don’t have ADHD. My access to treatment can be denied by a non-believer and then I’d have to fight to get it back. Or, what if ‘they’ were right.. what if I really have just been lazy and selfish all along? This is where my head spins to several times a year. It never gets less nerve wracking, even 30yrs after diagnosis.

[@podpoe]

💔

[@goldenhelmet403]

This is a great overview, but I really would like to know more about the specific genes that have been identified, how strong the specific associations are, and what probable mechanisms have been suggested for those specific associations.

[@drrodopszin]

The fact that ADHD has so many different symptoms and expressions and is on a scale wouldn't it already exclude the "just 1 gene" hipothesis, as it is not an on-off thing?

[@johnbehan1526]

Ah, would that it were so simple. A single gene for ADHD could still have lots of different outcomes because of interactions with other genes and the biological systems they code for. So, let's say ADHD was caused by one gene (maybe it affects how the dopaminergic pathway from the midbrain stimulates the frontal cortex and affects decision making). Other genes might affect the resulting ADHD (by making memory worse, or making distractions more distracting). The second set of genes isn't the root cause of ADHD, but in combination with the necessary ADHD gene, their effects might change the severity of your ADHD symptoms or the nature of ADHD presentation. So is a gene associated with ADHD an ADHD gene or not? Yes and no: some are going to be strong markers for ADHD because they co-occur frequently, but on their own, wouldn't predict 100% of ADHD outcomes. Some weak markers will just co-occur with the important markers in the population, but might actually do nothing. Some weak markers of ADHD are going to have such a significant effect on certain members of the ADHD population that they confuse the picture: you take them out of your analysis and it doesn't work anymore, but you might also find that most people who have the gene don't have any ADHD symptoms. Biostatistics is hard. And the diagnosis is by syndrome, so it is already hard enough to separate the population into "ADHD" and "not at all ADHD" in the first place.

[@emmylou.]

Epigenetics fascinates me! I wonder what has been passed down my line. I have done a lot of genealogy research of my own family tree and once I was diagnosed I looked at the stories of my ancestors in different light. I descend from many impulsive, risk takers . My 4x grandparents were either convicts (Australian here) or were immigrants who moved out mid 1800’s with zero possessions to farm. Moving down the tree there is family born out of wedlock, boxers, soldier, untimely deaths, my grandfather lied about his age and was at war by 17. I definitely think my adhd was passed down the family line siblings and cousins included. I’m the second generation off the farm so I think my adhd has presented in a very different way from my ancestors. Our methylated flags would be flying like the flags at the UN if anyone needs to study my genes.

[@rdklkje13]

Happy New Year to you too! One of the genetic aspects of ADHD that I find most interesting is the collagen connection. It’d be helpful to know how exactly EDS/hypermobility relate to ADHD/executive function and what this may mean for the development of new treatment options.

[@Queenread82]

YES

[@luperbsjr]

WHAT, there's a strong correlation between adhd and hypermobility?!!? that could explain a lot about myself

[@rdklkje13]

@@luperbsjr Yes, there is! But not much research has been done yet into the details of what exactly is going on. The general role of collagen in human neurology isn’t even well understood at this point, let alone variations such as those present in hypermobility and ADHD. Some interesting studies are being done but this is all fairly recent work.

[@Queenread82]

@@luperbsjr That is how I started the path to an ADHD diagnosis. There are so many comorbidities!

[@goldilockz6517]

Great point

[@jimwilliams3816]

Thanks for this! I have suspected the multiple gene variant model as a factor in the variability of both autism and ADHD expression - in other words, the spectrum aspects of both. If you look at the list of criteria, and the presentations, it seems plausible that many factors are at play. I’ll note that, while it may now be becoming a bit dated, the 2 Molecular Genetics lectures in Robert Saplosky’s Human Behavioral Biology series (2011) on the Stanford KZbin channel was a useful primer for me on how various gene expression mechanisms occur. It’s fairly technical but Sapolsky is good at clarifying these processes. If you’re into this stuff.

[@basiabarbara3365]

Thanks!

[@christinekinn6178]

You mention genes being methylated, or not, but i wonder if any studies look at variances in the MTHFR which can lower methylation rates, and affects neurotranmitters. It is highly correlated with autism.

[@blastypowpow]

I am homozygous for the MTHFR gene. I have 70% reduced folic acid conversion. I take B vitamins that have actual folate and other methylated B vitamins. My doctor discovered it doing genetic testing for psychiatric medications. The problem is that I often forget to take it. My mother likely has at least one allele for MTHFR and wasn’t taking folic acid or folate when she was pregnant with me. She was also 29 when she had me. I’ve been diagnosed with ADHD and recently my psychiatrist and I have chatted about ASD as I took some online tests that are the same ones they use to test for ASD in psychiatry and I scored pretty high. ADHD doesn’t account for a fair amount of my symptoms. I’m 44 and just received an ASD diagnosis. I’m not sure how it was missed for so long. I’ve often wondered about MTHFR and ADHD/ASD. I’ve also had GERD since I was 5! I don’t know how any doctor didn’t connect some of these things.

[@themobbit9061]

Fascinating. Thank you.

[@denalraab]

It's interesting to learn that there seems to be an increased risk for a mutation as the age of 'parents' increase. I wonder if there is any sort of correlation to reduced overall estrogen, as the egg supply is diminished. Is the existing level of hormone a factor in gene expression of adhd? Does this factor into how a resulting female child might be affected at the various hormonal stages over her lifespan? Per your recent video on the effect of fluctuating hormones and how EF is impacted, I could ask a million more questions. I hope the research can find the connections. Exciting!

[@Intothelight72]

Thank you for this Dr Barkley! Your videos are always very much appreciated, I always look forward to your content. I’ve learned a lot from you over the years and have been able to better understand my son who struggles with adhd. This is very interesting….we have some adhd in pur extended family on both sides, but neither his father nor I have been diagnosed and neither of us appear to have it. Thanks for making a such a complex subject easier for a layperson to understand. Happy New Year!

[@obgfoster]

My grandfather was in his 40s when he had my mom, who I think had ADHD. (and she had some variety of mental illness that required several hospitalizations). I have wondered about grandparents ages combined elevating risk.

[@pmilosev]

Thanks!

[@ilovetosmile]

dripped out in this vid bro stay healthy 🤟🏼stay cool 🔥🔥

[@patriciajump9511]

Omgosh, that is a lot of complexity.

[@marko_z_bogdanca]

Assuming that ADHD is genetic, it appears that it requires quite a wide range of genetic modificications. Isn't it a strange coincidence that the issue applies to brain only?

[@patrickkelly737]

Russell Barkley, the Sigmund Freud of ADHD. Dr. Barkley is starting to look like Freud and they both had massive influence on their fields. I guess that makes Ned Hallowell the Carl Jung? I say this with deep respect and gratitude for the two of them

[@karladolman9664]

Except of course Dr Barkley uses empirical evidence and Freud's theories are not founded on any empirical data and rely primarily on subjective interpretation and speculation, they have been labelled as pseudoscientific.

[@TeslaDanser]

Im seeing a clinical psychologist in the morning. Is the adhd symptom checklist from w.h.o enough to bring forward to aid diagnosis? Any info very much appreciated. Quite lost in all this

[@russellbarkleyphd2023]

It is only a screener for possible risk and inadequate for a diagnosis. That requires interviews, ore complete ratings, history, etc. as my video on this channel on adult assessment makes plain. Good luck tomorrow.

[@TeslaDanser]

@@russellbarkleyphd2023 thank you so much for you reply. You're a beacon of light for so many, myself included. I really think I have been heavily and blindly impacted by it all my life. The subject in ireland as for nearly all mental health issues is not well understood it seems,from previous experiences, and somewhat of an unwanted hot potato. Standards have improved though but that's easy to say for those still alive.

[@stmcm]

Thank you for the timestamps, that helps a lot when re-viewing the video. :) I have a question: I am 40 years old and have ADHD. My partner does not have ADHD. If we decide to have a kid, it seems pretty likely our child will get ADHD due to the fact that I have it and my higher age. Is that right?

[@russellbarkleyphd2023]

Assuming that you have the genetically transmitted form of ADHD the risk is 8x greater of having a child so that would be about 40-50% chance given current research on the issue. If you acquired ADHD, then it is not genetic and the risk is much lower.

[@chrisarchibeque8584]

@@russellbarkleyphd2023so it appears that the genetic factor for ADHD arising in an individual is more likely to come from the maternal side?

[@tonyprivat807]

Genes express themselves not as individuels but as a group. Same as animals. We all have variants to cumber with evolution, that is evolution. Genes are how we are precured, how we treat the body with food, mental training and physical is everything.

[@tonyprivat807]

Autism is new and im 100% sure it has to to with wave radiation over time. Or else it is some form of pollution from the world war 2 or new industrial age after that.

[@paysonmuller1505]

🙏🏼

[@trewdat361]

Should mandatory ADHD and Autism (and other common psychiatric conditions) screening of children be put in place? I feel as if the benefits of diagnosing patients earlier would heavily outweigh the cost and cons of mandatory screening. Happy new years Dr. Barkley!

[@joelwilliams3115]

Good luck at the gym dr Barkley. I’m a personal trainer so if you need help, let me know

[@Indiekid-1976]

I discovered in the last year, aged 47that I both have ADHD and was thrown at the wall by my father when I was aged 11 months old. I discovered partly that I have ADHD through exploring this with my children who both also have this disorder, I realised most of what was discussed applied to me. I know that ADHD can be caused by traumatic brain injury, can this kind of ADHD be passed on genetically? I don’t know enough about my father or his family to ascertain whether he had ADHD traits and passed these genetics on too or it was purely acquired from this TBI…

[@RoSa-kr8hy]

A lot of people with ADHD have comorbidities,so maybe your father also had ADHD and another condition that contributed to his behavior. I am sorry that that happened to you. I hope someone here has more answers for you.

[@obgfoster]

Emotional dysregulation + impulse control issues right there!

[@publius9350]

Dr. Barkley talks at times about how those with ADHD are more likely to commit domestic violence. Also, things that cause executive function issues don't exist in either/or fashion, but stack, if I understand correctly. In other words, you may have ADHD in the family, and your ADHD may be worse due to the TBI. In that case, your children might also have a higher chance of ADHD, but if you raise them right, they might have a less extreme case of ADHD - this is also true for issues like generations being exposed to lead - leaded gasoline was horrible for everyone in those generations and remained in the environment after. I don't know epigenetics enough to say how trauma can carry over, but generally, you should understand there are reasons your children might have ADHD, but you can make the extremity of it less by being as good a parent as you can.

[@TinaWiman]

Brain injury from trauma cannot be passed on genetically.

[@truth-hurts3089]

I hate having ADHD, it's been a bomb shell to my life getting the diagnosis and hate the fact I think I've passed it onto my 6 year old son......however all this gene stuff makes me wonder what the world (Western) would look like with no ADHD'ers. I suspect society would be more robotic and compliant. Just what Gov want I guess.........

[@chrisarchibeque8584]

Anyone ever noticed that he looks like Dr. Phil? Once you see it you can’t see it. 😂

[@truth-hurts3089]

All this ADHD stuff makes me feel "broken". But I know I'm not broke I'm just not suited to Western society (British in my case). Think I'd live better in a jungle or catching fish off a house on stilts with spears all day.

[@stephen304]

Haha that's me lol better designed to react to immediate dangers and needs than plan and execute modern day complex timed productive living. Productivity is overrated.😅

[@Adulthoomanfemale]

I feel this way too. I feel like I evolved for Paleolithic life, not the Neolithic and beyond.

[@user-eq7yy3jl1n]

I feel I can die happier in war than of old age💀

[@truth-hurts3089]

@@user-eq7yy3jl1n I think I understand your reply. Sat rocking in a care home being fed baby food, eating day time tv and wearing incontinence pads doesn't really do it for me either. Give me a bullet over that anyday.

[@caitiecatcreates]

So if I'm ADHD, my father was ADHD, but my husband is not ADHD, what are the chances my baby boy will have ADHD? 🤔

[@ScienceisRadAF]

I don’t think we know that yet. Anecdotally, I have ADHD, my kids’ dad does not.. and I’m 3 for 3 with neurodivergent offspring.

[@d.d.d.a.a.a.n.n.n]

The probability also depends on if he has blood relatives with ADHD and what genes he carries. Only one of my parents has ADHD, but neither of his parents have ADHD, while my parent without ADHD has a parent with it. One of my siblings has ADHD along with me, and our other sibling is neurodivergent but his childhood ADHD diagnosis was a very likely a misdiagnosis, and his neurodivergence is something else

[@carpdirector6836]

I’d say there’s a pretty good chance your son will have it, too, but that’s purely a guess on my part. In my case, I have ADHD, as does the brother I share a mother with. My other brother, who shares my dad with me, does not. My mother died when I was little so no idea if she had it. As it turns out, my husband has ADHD and two of our boys do, too. Our middle son has some ADHD symptoms but not enough for a diagnosis. We don’t know of anyone in my husband’s family with ADHD, but, interestingly, I’ve noticed some symptoms in his dad over the past few years that make me wonder. I think the most difficult part in determining the genetic component to ADHD is that symptomatic behaviors are only recently being recognized. In older generations, ADHD symptoms were considered to be more “personality quirks” so today’s scientists don’t have sufficient scientific data to work with.

[@leahcarlson1255]

What if school just sucks?

[@Sujetsi]

All the more evidence that countries should facilitate their peoples having children earlier.

[@insidiatori9148]

The adhd genes stop where I exist. No children for me.

[@drrodopszin]

We say this, but no narcissistic psycho ever says this. We overvalue productivity and undervalue being kind. If you are kind, if you have a good heart, if you care about your environment (human and natural), you have all the good reasons to have kids.

[@jimwilliams3816]

Productivity as the major issue with ADHD is the stereotype, but not always the reality, and anyway I have much more going on than just ADHD. My concerns with being a parent centered around difficulty connecting with people, especially infants (probably partly autism), and emotional dysregulation, at least partly but probably not completely ADHD. I judged that these things, along with some others, would make me a poor parent, and looking at my trajectory from a position late in life I feel sure this was the right decision - and it’s a personal one. It’s easy to look at narcissists and psychopaths and suppose that they are “bad at heart,” whereas perhaps someone like me means well. Mental health is not that binary, though. My meaning well has not meant that I have not done some of the types of damage to family members that narcissism can cause. Again, I’m not suggesting that people with ADHD or other mental health struggles ought not have kids, even if the risk of heritable disorders is higher. Many are good parents, and have great kids, whether neurotypical or not. But in my case, the way I utilized my good heart was to judge that it was not enough, that my good intentions wouldn’t keep me from being a problematic parent. As a personal decision, it’s perfectly valid. Lots of people of all neurotypes make the decision not to have kids, and it’s unfortunate that this is regarded as selfish in some quarters. We’ve octupled the world population in about 125 years, IIRC. Having kids should no longer be considered a moral imperative.

[@insidiatori9148]

@@jimwilliams3816Thank you for your message, it’s quite beautiful. Honestly I have been thinking a lot lately about everything people call crucial in modern world like certain cognitive ablities, social standard behaviour. While the most important factor will always be the upbringing of a person along with his passion, curiosity, emotional stability, rationalism, selflessness, trustworthiness, flexibility and the ability to stay true to his own character. Perhaps these comorbities can be prevented/mitigated by true parenting and acceptance. Sometimes I ask myself how much less my adhd symptoms would have been if I hadn’t always felt pressure, uncertainty or hadn’t used those drugs in adolescence or anxious feelings. I have felt like a chess piece that didn’t know it’s actions, feelings, vulnerabilities and such and maybe my future generation would not need to have these feelings if counciled correctly with warm support.

[@blastypowpow]

I’ve chosen the same. I’m 44 and I wouldn’t want to inflict my ADHD/ASD on a child. It is hard enough for me as an adult and was super hard as I was growing up. No one seemed to be able to catch either disorder until ADHD was Dx at 17. Didn’t catch my ASD until just a few months ago. Edited for typo