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You will see the 10 domains listed there and the first four of which you will recognize as they form. First three, at least form the bulk of the diagnostic criteria. That's the attentional activity and impulse related issues. The fourth domain, emotion emotional dysregulation, is widely accepted as being a core feature of adhd, despite the fact it's not included in the diagnostic criteria. However, domains 5 to 10 are less often explored and discussed, including the reward system, the sensory system and sensory processing issues. How the ADHD brain deals with time issues around time appraisal, the biological disruption of the sleep, wake cycle or circadian rhythm. And again, importantly for Today, the immune system, the immune function and inflammatory status. Clear evidence of dysregulation in ways that I'm going to explain in just a moment. And finally, dysregulation in the way that we expend and use energy, often in a boom and bust type of pattern, and how our arousal system works. Arousal is central to understanding many of the problems in ADHD. So this is the 10 domains of dysregulation model. I introduce it formally in my book and it seems to be attracting lots of interest. I'm going to focus today on domain 9 for the most part and try and build a picture for you. When I started to look into this area and really understand the overlaps between ADHD and various aspects of inflammation, I felt it was appropriate to synthesize this into a model. The neuroinflammatory hypothesis of ADHD is actually what I refer to it as. And I'm just going to orientate you to to some of these connections so that you understand how we know that ADHD and inflammation are overlapped. Well, first of all, and probably most importantly, is that ADHD coexists with a whole range of inflammatory conditions, including allergies and autoimmune disorders. There are many others and I'm going to talk about them in just a moment. Numerous studies have shown that there are inflammatory markers, which basically means tests, usually blood tests, that mark levels of inflammation. There are many of them and many, many are raised in individuals with adhd. At a group level. There are issues linked to inflammation, including premature birth, low birth weight, neonatal infections that have been shown to increase the risk of ADHD and moving the focus from the fetus or the neonate to the mother. Maternal inflammation, whether it's through allergy, autoimmunity or dysfunction of the metabolic system, including obesity, has been shown to increase the risk of ADHD via inflammation passing through to the unborn child. We know that gut dysbiosis or imbalance of the gut microbiota or microbiome which is associated with inflammation, links with ADHD and other neuropsychiatric presentations. There's some evidence, interestingly, that methylphenidate, one of the main stimulants we use to treat adhd, may actually reduce inflammation in certain cases. However, these findings are contradicted in some other animal studies. So really this is not a clear cut finding yet. There are other animal studies that suggest links between ADHD related traits and inflammation. We know from a few different studies that that food allergies and intolerances which contribute to inflammation in the gut. And inflammation across the whole system may potentially drive ADHD symptoms, worsen ADHD symptoms, with some findings actually that again contradict. So again, we've got lots more to learn in this area. There are genetic studies showing that certain genes that are linked to inflammation occur in higher rates with those with adhd. And loads of indirect evidence, things like vitamin D, which is anti inflammatory, being lower in adhd, and then iron deficiency and low ferritin being more common in adhd, again with serving as markers really for inflammation. We know that certain children with ADHD have lower levels of fatty acids, which is the link with omega 3, and the supplementation with omega 3 has been shown to be effective in certain individuals, probably those with lower levels. So there's loads of evidence to tell us that inflammation is linked to adhd. But the real challenge is understanding the mechanism by which that inflammation is happening. And hopefully I'm going to share some theories really that need further study. I just want to mention that each of these 10 items is backed up by lots of research. You can see just the first two, a number of different studies going back to 2000, probably 2005 or even earlier, showing these findings over and over again. So what about the conditions, the inflammatory conditions that have been shown to be occurring at higher levels in those with ADHD than you would expect in individuals without adhd? Well, right at the top of the list is allergy and what we refer to as ATP atop is asthma and eczema, et cetera. So whether it's hay fever or asthma or eczema or dermatitis, we see higher levels, significantly higher levels occurring in individuals with adhd. The same is the case for autoimmune presentations and disorders, psoriasis being one of them. Autoimmune thyroid diseases is particularly common and diabetes, which is an autoimmune presentation type 1 diabetes. And the condition that I referred to at the beginning of the talk, which is pandas, which is basically an autoimmune brain condition where the system mistakenly attacks a part of the brain called the basal ganglia, causing inflammation in that area. And the symptoms that I mentioned earlier, many infections, including Covid, have been linked to to adhd. Most of the studies have been done in children. And links with gastrointestinal, respiratory and urinary tract infections are coming up commonly for different reasons. Sexually transmitted infections associated with adhd, but that's less likely to be through an immune process. But it's possible as well. Immune deficiency has some links. Studies by researcher Merzon and his team and the list goes on. Metabolic issues, including obesity and metabolic syndrome and type 2 diabetes have been shown to be linked. Various neurological and sleep related issues, including epilepsy, Sleep disordered breathing, which is otherwise known as sleep apnea and migraine, have strong links with adhd. And then there are this cluster of connective tissue pain and fatigue disorders, whether it's fibromyalgia, chronic fatigue syndrome, chronic pain, other forms of chronic pain and hypermobility, people who have lax joints, which I'm going to expand upon shortly. We've talked about the raised inflammatory markers. Here's some of the markers that have been shown to be increased in those with ADHD as well as autoantibodies. So these are the things that drive autoimmunity and they attack various parts of the brain and in some cases the body. There are some, again, some contrasting or contradictory findings. There was a study showing no association between an inflammatory marker called CRP and ADHD risk, but on the whole we found that higher inflammatory load increases the risk and severity of adhd. My question that I want to pose to you is if we broaden out this frame and we start looking more at these patterns and these connections, could it be that we are looking at a much bigger and broader syndrome with ADHD as just one expression? It's controversial, I know, especially as there's quite a lot of evidence showing that ADHD definitely is a brain related problem. But I'm arguing that it's also a body related problem. And I'm going to show you some very exciting ideas to explain that. I'm just going to read this extract from a poem that I wrote called Systemic Toxicity. You'll be able to find it online if you're interested. But I think this little aspect of it, it's quite a long poem, but this little part of it I think really captures what I'm trying to communicate. So what can one do for when faced with this mess, I know not the answers, I really must confess, but let's take a step back. Notice the patterns, ask the right questions and then make connections. A systems perspective is what is suggested and what might you discover? A cluster of syndromes that journey together, so common, yet hidden from all but a few who often themselves are suffering too. A cluster with lax joints right at its core. But with it there often comes a whole lot more. A cluster so toxic, inflaming the brain and draining the mind of the joy and the drive that keeps us alive. So taking the focus slightly away from inflammation, specifically, these are the clusters of physical health Problems that occur in adhd actually, ADHD across the board, but many of the studies have been in adults. So there's the immune and the atopic conditions which we talked about. There's cardiovascular problems and some of these are linked to high blood pressure, but others are linked to what we refer to as autonomic nerves, autonomic issues. So issues with the autonomic nervous system, where often the problem relates to not enough blood getting to the brain, the neurological issues, sleep problems, epilepsy, migraine and possibly neurodegenerative problems, although the research is really early there. And then there's the conditions linked to living a lifestyle, the lifestyle aspects of ADHD that might not be so healthy. So whether it's drinking, smoking, drug use, sexual stuff, that clearly that's going to drive some illness, you might have medication related complications. Although I must say that the medications we use in ADHD in general are very effective and seemingly very safe as well. And then hypermobility, and this is an odd one. Why hypermobility and what is hypermobility? I just want to make the point that there are certain physical health problems that are explainable, really. If you don't sleep much and you don't eat healthily and you use substances and you take risks, you're going to have various physical health problems and of course things linked to the medication. But there are some conditions that are less easily explainable that need a different model to explain them. And these include, as I've mentioned, asthma, allergic rhinitis and other allergies, a whole range of autoimmune conditions. We've touched on sleep disordered breathing, abnormalities of the eye, migraine and hypermobility. And just to make the point, if you have a great study by a researcher from the UK called Jessica Eccles and her team showed that approximately 50% of individuals with ADHD are hypermobile. And if you look the other way around, the relationship is really strong. My question when I started seeing so much hypermobility in my patients many years ago now is why? How, what? So I'm going to focus briefly on hypermobility for a moment. And this is a typical patient with ADHD. This particular lady who was almost 30 years old had some features suggestive of autism. She was hypermobile and had a whole host of joint related problems and pain related issues which are listed up there. She also complained of getting dizzy and lightheaded and standing and getting fast heart rate when she stood up from sitting. She had some gastrointestinal issues and some allergies as well. So Let me just orientate you. Hypermobility is a result of the connective tissue issue or abnormality. Connective tissue is a tissue which holds the body together. And one of the main proteins is collagen. And when collagen is defective in some way, individuals will have lax joints, but they'll also have lax tissues across the whole body. It may not be a problem. Asymptomatic joint hypermobility. Not everyone with hypermobility has issues or illness or pathology. But those that do fit into these two categories, Ehlers Danlos syndrome and hypermobility spectrum disorder. And you can see it's a affecting every part of the body, all the systems of the body, because all the systems of the body are held together by connective tissue. And this is my other daughter, Mia, who is very hypermobile. And you can see she can do various maneuvers with her fingers and her arms. She can touch the floor flat with her hands. And this is her bruise. She had a bruise, and she showed me the bruise. And you could see the blood is literally tracking through the tissues. And because they're lax, they're open, they're more. So you can see that every aspect of the system, and here's all the places that there's collagen in the body. It's not just about joints. It's not just about ligaments and tendons. And, you know, joint laxity is common, 10 to 20, maybe even 30%. But when it occurs with other problems, as I said, it becomes a disorder. Now, what we've seen or we understand, is that these people with symptomatic hypermobility syndromes cluster together with those with something called dysautonomia. This is disorder of the autonomic nervous system and something called mast cell activation disease, which is essentially hyperreactivity of the immune system, and all of these things in different ways. And this is not the time to dive into the detail here. Drive neuropsychiatric symptoms in a range of them, and I'm going to show you some of them. These problems also are strongly associated with gastrointestinal problems and with autoimmunity. So we're seeing a picture building here where connective tissue, immune dysfunction, autonomic dysfunction, gastrointestinal problems are clustering together in this network. And I developed a model that pulls all this together. And I'm not expecting you to look at this slide and understand it all now, but what I want to show you is that this triad in the middle that I introduced you to, along with the gastrointestinal Autoimmunity are, for different reasons, in different ways, driving mental health and neurodevelopmental symptoms, not simply just because of dopamine and noradrenaline levels in the brain, but because the brain's not getting enough blood and oxygen and that the inflammation in the body is going to the brain. And you can see down the right column here, all of the different mental health type issues that are linked to this cluster. And the question really is how much of mental illness and how much of neurodevelopmental problems are being driven by body based issues such as brain perfusion and neuroinflammation issues. And draw your attention here, really to this category here, which is the attentional and memory problems often lost in the term brain fog. How does chronic brain fog differ from adhd and how much overlap are we talking about? These are the mechanisms that I mentioned, which I will elaborate on briefly. Dysautonomia, the autonomic nervous system not functioning properly and neuroinflammation. You can see someone standing up and the blood's just not reaching the brain in the same way as it is when they're sitting now. So this is the autonomic nervous system, the sympathetic and parasympathetic, and they are in opposition. One is the stress response and the other is the relaxation response. And the system is both one of the main threat response systems of the body, but it's also the way that blood is moved around the body, including to the brain. And when you have dysautonoma, often you'll experience symptoms on standing, standing upright, not getting enough blood to the brain and then getting symptoms. And one of the groups of disorders, one of the conditions in dysautonomia is pots, but there are many others. And like adhd, dysautonomia can start in childhood, it can continue through life, and it can cause many of the symptoms that we understand to be adhd. Let's move the focus to inflammation, which is the main topic of today. This is a mast cell. It's a form of blood cell, white blood cell, but one that doesn't generally reside in the bloodstream, but in the tissues of the body and specifically at the environmental interfaces of the body where the body meets rest of the world. And these are very important cells. They are often referred to as the first responders. They have loads of receptors on their surface that register various different threats from the outside world and some from the inside of the system and release a whole concoction of different chemicals into the tissues. Or into the bloodstream that are there to try and deal with the threat. You can see where these red dots are here. Eyes, ears, nose, throat, the respiratory tract, the gastrointestinal tract, the genitourinary tract, the skin. These are all the places where threats reside. Whether it's infection or allergy or injury or vibration or pressure changes, these cells are phenomenally effective at picking up any threats. And the problem is, in some people, they are jumpy. They respond too quickly, too easily to potential external threats. And if you're interested to see in real time what a mast cell looks like when it's activated, it goes from looking like a normal closed cell to literally breaking open and releasing all these chemicals into tissues. I can't show the video on this webinar, but you can go to YouTube and type in this text here on the right side and you'll see something quite phenomenal. When people have mast cells that are misbehaving, it's referred to as mast cell activation disease. And until relatively recently, we only really thought about some rare conditions where the mast cells act much like a cancer, they proliferate excessively. Where, however, there's another group of conditions where the mast cells don't proliferate, they just release excessive amounts of chemicals. And this is referred to as mast cell activation syndrome. This is the mast cells. And you can see when mast cells release these chemicals, whether it's histamine, which is the best known one, or cytokines or interleukins, or a whole host of other things, they have impacts on every system of the body through this widespread inflammation. And many of the things that we conditions that we present are going to be doing so through this mechanism. We know about mast cells. Mast cells are what release chemicals in allergies, what make your lungs tighten up in asthma. Histamine causes many conditions that we see all the time, but there may well be more, and particularly there may well be neuropsychiatric presentations. In fact, there are, and I'm going to show you how. So, mast cell activation syndrome, still controversial because it's only described about 15 years ago. It can be secondary to other problems like allergies or infections or. Or it can be a direct problem with the mast cell through genetics. The key thing is that inappropriate activation results in lots of chemicals released and wide ranging symptoms, allergic type, inflammatory type symptoms. And normally the story is people have maybe some allergies or ATP or some odd pockets of inflammatory issues during childhood, and then something comes along, flares up the situation and causes a whole host of symptoms causes the mast cells to really upregulate and start and not come back down to baseline often. Importantly, this is associated with prominent neuropsychiatric symptoms, many of which overlap with adhd. What triggers mast cells to release chemicals? Well, infections or fevers, including Lyme disease or glandular fever. This is the story where people get glandular fever or Lyme disease or Covid and they get long glandular fever, long Lyme disease or long Covid. Much of long Covid is explained by mast cell activation, but equally physical stimuli like pressure or friction or even exercise, stress or trauma. You know, mast cells have receptors on their surface for stress hormones. So this is the link, I think with between trauma and physical health problems. Stress drives inflammation, allergens, drugs, toxins, certain foods and alcohol, where usually ones that contain lots of histamine. Changes to the environment, particularly issues with mold and possibly with electromagnetic radiation, although again a controversial area and importantly particularly for women, the changes to the hormones, whether it's changes over a month or changes around the menopausal period where hormonal shifts take place, causing mast cell activation, particularly estrogen. There are receptors for estrogen on mast cells. Now this has been studied for some time. It takes a long time for this information to permeate through. But there's a number of neurological conditions on the first line that have been linked with mast cell activation and various mental health and neurodevelopmental conditions. And in your own time you can look up the detail here. I just want to illustrate that this is not coming out of the blue. And again, many findings here. I've listed seven big ones that link mast cells with neuropsychiatric presentations. And again, I'm putting this here to show you that there is lots of evidence to show these connections. It's just we haven't been thinking about them in ADHD until very recently mentioning that linking mast cells to adhd. There haven't been studies on this demonstrating these connections directly. But one very insightful review by a group of interestingly complementary medicine practitioners in China published in 2020 that put forward the question could ADHD be a neuroinflammatory presentation involving mast cells? And here are all the reasons that I think support that claim. And it's really circling back to the earlier slides which show these connections. And again, you can look in more detail. We know that toxicity drives mast cells, drives inflammation, toxins are highly inflammatory and they get into the body in different ways and drive chaos. And with in terms of the autonomic nervous system. They damage barriers, gut barriers, blood brain barriers and cause toxicity in the brain. And is it possible that people with ADHD as a result of their immune dysfunction in many cases are like canaries in the mind. They get affected by toxicity earlier than most people. On a group level, not everyone's going to be in this camp. And to support that we've seen number of studies showing that there are multiple toxins that are linked to adhd from lead through to even paracetamol taken during pregnancy to pesticides and air pollution. Most of the time we study toxicity and we find its links with adhd. And this was in a very big document collating all the important evidence around ADHD published by Stephen Ferreau. I just want to draw attention to something that doesn't get much attention. Coming to the last part of the last few slides here. Indoor air toxicity is something that we don't look at enough. We often talk about outdoor air toxicity inside the home. There are many problems, increasing number of problems with the increasing chemicals that we bring into our lives and mold and the toxins that mold produces. I can tell you personally from personal experience and also from really diving deeply into this is a massive driver, a massively under recognized driver of illness, particularly neuropsychiatric illness. I think there are many people walking around with severe long standing chronic illness as a result of mold due to water related damage, powerful immune effects, powerful effects on the mast cells and environmental toxicity, whether it's mold, heavy metals, infections are working directly impacting the brain, but also through their impact on mast cells. Finally, I just want to draw attention to this genetic study. This was the latest study looking at in this case almost 40,000 people with ADHD and many more controls. And they're looking to see what genes or which genes stand out as being higher, more commonly present in those in the group with ADHD. And they found 27 essentially genes that crossed this line of significance. And what we read in the study was that these genes have lots of effects on the brain. Here in this column here I picked out three of these strongly linked genes you can see on the far column here. It shows that these are highly significant strong associations with adhd. And the study understandably focuses on all of the brain functions that these genes have. But if you dive deeper, you realize that genes don't just do one thing, they actually have multiple functions. And these genes just as an example and you can find many other ones of those 27 I've just picked out three have powerful immune related issues and issues linked to Connective tissue function I just listed here including mast cells, including hypermobility syndromes. But the point is I'm trying to make is that we find what we look for. If we're looking for stuff related to the brain, we'll find stuff related to the brain this first column. But if we broaden the search we realize that the problem is far broader than just the brain. It's a system wide issue. Anyway, that's enough from me. I just wanted to introduce you to my book. It's not specifically on these issues, although I do introduce these concepts and ideas. Is really more about how to live really well with ADHD and it's doing well. It's been top in Amazon for psychology and psychotherapy for on and off for the last few months and I encourage you to have a look and see if it interests you. As I said, I'm the medical director of the Grove Practice and we run various trainings. A one day workshop for individuals with ADHD or who suspect they have ADHD and then for professionals, a three day course called a Certificate in adhd. And the plus is for all of this other stuff that often doesn't get mentioned. Feel free to come along and have a look. The first cohort's full but we've got some new dates out there and to be honest, they're getting full as well. We are going to put more dates out if people are interested in. I want to thank you very much and I look forward to some questions.
