620- ADHD and Inflammatory and Immune System Disorders: Exploring Links and Risks

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0:26Welcome to the Attention Deficit Disorder Expert Podcast Series. by Attitude Magazine.

0:35Everyone, I'm Carol Fleck, and on behalf of the Attitude team, I'm delighted to welcome you to part one of a two-part series on ADHD and immune system disorders. Today's presentation is about inflammatory conditions and their ties to ADHD. Next week's presentation will focus on how gut health influences ADHD symptoms. Today, we are delighted to present ADHD and Inflammatory and Immune System Disorders, Exploring Links and Risks, led by Dr. Beth Krohn. Dr. Krohn is a licensed clinical psychologist in private practice and a research scientist at the Icahn School of Medicine at Mount Sinai in New York.

1:26She manages the Clinical and Translational Studies Program at the Center for Excellence for ADHD and Related Disorders. Dr. Crone is currently launching two clinical trials. The findings will be used to develop evidence-based treatment guidelines for providers treating children, adolescents, and adults with ADHD. Dr. Crone is a member of APSARD, the American Professional Society for ADHD and Related Disorders, and she's on APSARD's task force charged with developing the first-ever U.S. guidelines to diagnose and treat ADHD in adults. A growing body of scientific evidence suggests that ADHD and asthma, skin allergies, gut problems, POTS, and other autoimmune disorders may be more closely connected than previously thought.

2:20This presentation will examine how biology, psychology, and social environments all play a role in the onset of these conditions. If you value the work we're doing here at Attitude to support the ADHD community, please consider subscribing to Attitude Magazine. Your subscription helps us to continue providing trusted resources and information to help you and your family. So without further ado, I'm so delighted to introduce Dr. Beth Krohn. Thank you for joining us and leading this important discussion. Thank you so much for having me here and I'm going to jump in really quickly. I have no financial conflicts of interest.

3:05We say these things on academic presentations so that you know that nobody is paying me to come and promote anything. And the work that I've done here is my own and it's for you. In today's conversation, I'm going to provide a conceptual and historic framework for why we examine immune and inflammation in ADHD. We're going to look at some of the associations between ADHD and physical health that are kind of documented pretty well in the research and consider some of those underlying mechanisms. The questions that we're going to try to answer today, and it really what matters to you, is does recognizing the role of immune inflammatory processes change the way we think about ADHD and having ADHD?

3:57And are there opportunities for treating ADHD or these inflammatory conditions a little differently to get overall better care? And what the next steps are for acting on the information? So we're going to start off with a little bit of history and a little bit of science, and we're going to kind of wind down to what you can do about it right now, what's possible and what's not.

4:26All right. So you don't have to read the slides. I'm going to summarize them as we go. The first slide is talking about neuroinflammation and the brain. So neuroinflammation in the central nervous system is part of a normal developmental process. So in order to form the nervous system, there are innate immune cells like microglia and astrocytes that build the brain and the spinal cord starting from conception and straight through life. There are genetic programs in these cells that get activated and they cut back on extraneous connections that don't need to be there and they cause the brain to be able to learn, to grow, and they shape healthy brain function.

5:25They also can recruit immune cells from outside of the central nervous system and in case there are illnesses, if there are viruses or bacteria, anything that migrates into the central nervous system that needs to be fought. So these innate immune system cells that are part of the central nervous system and some of these secondary immune cells that are outside the central nervous system keep a healthy brain. Now, if those innate cells are programmed to make weaker connections or get hijacked by viruses or other pathogens that cause damage, it can cause low-level chronic inflammation, and it can also cause severe damage.

6:17Now, when we're talking about ADHD, we're talking about these kinds of subtle low-level irritations more than a severe problem. Severe problems are things like Zika, where you have very serious disease. And ADHD, we're talking about more subtle processes. Chronic low-level inflammation outside of the brain and in the rest of the body can also cause vascular problems. Those vascular inflammations can increase the permeability, how easy it is for pathogens and viruses and other things, including external immune cells to get into the brain cavity into the central nervous system now that vascular permeability is kind of a key component when we talk about stress related disorders and brain fog and anxiety and depression and we can think about that in context of certain comorbidities with adhd but we don't necessarily think about that as a core piece of ADHD in all people or possibly even most people.

7:34So talking about neuroinflammation, neuroinflammation isn't always bad, but unchecked neuroinflammation, chronic neuroinflammation can be bad. Stress can be a driver of that kind of inflammation in a classic biopsychosocial model. So these models are all over in psychology literature. Stress, whether it's a physical injury or an illness or an environmental toxin, or just those kind of socioeconomic problems that pile up, relational issues, job stress. We have that fight or flight or tend or befriend response, that activation of that neuroadrenergic system. And we have the hypothalamic pituitary axis, which produces cortisol and a natural anti-inflammatory process, and these play off each other.

8:34Now that SAM activation, that fight or flight, that neuroadrenergic activation is one of those critical players in that adrenergic response that's treated with some of our medications for ADHD, like guamphacine, that's even ademoxetine to an extent. And so there's always been this hypothesis that some of this activation may be influencing cognition through inflammatory processes. Now, this is a model that we use for all people with or without ADHD. interesting it's how stress influences cytokine levels and how it increases microglial activity through those cytokines those microglia are some of those innate nerves immune cells in the brain and how that can over prune or damage pieces of the brain and we see prefrontal cortex changes on MRI based on some of this upregulation of these inflammatory markers from chronic long-term stress in anybody, including healthy people or typically developing people as well.

10:05Now, you can see that there are some interactions through the gut and some of these are through cytokines which are actors and messaging molecules in the immune system and some of them are actual cells like microglia or t-cells that can cause these functional changes and on here what i did was i kind of put in a few key theories of where weaknesses are in adhd from catecholamine kilinergic function, meaning dopamine hypothesis and noradrenaline, norepinephrine hypotheses, the dopamine hypothesis of ADHD and places where if the ADHD brain has inherited some weaknesses, this classic biopsychosocial model of stress causing functional changes on MRI and physical changes in the brain, if we have some weaker substrates that we've inherited with ADHD, then these effects are more pronounced.

11:20And executive functioning and self-regulatory depletion, some of those motivation problems, anhedonia, cognitive issues, poor mood, and stress sensitivity would be greater in context of ADHD under stress. So there's been this kind of historic interest in it ever since cortisol was identified. There was in the 1980s to 90s the allergic cholinergic theory where people were assuming that allergies and cholinergic dysregulation through histamine had caused... histamine intolerance is not the same as allergies had caused adhd um and they were later shown that it there was no evidence that allergies were causing adhd but we start to see some exploration of co-regulation um in the 2000s looking at immunoglobulins which are allergy related and eczema related and in 2013 and the 20 teens looking at interleukines and asthma and allergies and atopic dermatitis and people were looking for these molecular pathways because science was evolving and new asses were developed to let us look at these things more closely and we weren't finding consistent results.

13:05Why do we care about the HPA so much and why is there that persistent focus? ADHD involves those weaknesses of the prefrontal cortex circuits and there needs to be a precise balance of norepinephrine and dopamine to maintain attention and stop impulses. now we have this york dodson law for all people with or without adhd saying too little stimulation too little dopamine and norepinephrine you have no attention you get an optimal level for your personal biology you can focus and too much is stress you again lose focus now the hpa regulates that and indirect effects of these imbalances are disrupted sleep-wake cycles, disruptions in hormone signaling, and things that occur with greater frequency in ADHD.

14:10now ADHD is known to be a neurodevelopmental disorder not a stress disorder and because of that we know that there are reasons these stress hypotheses don't exactly map on to ADHD being a neurodevelopmental disorder means that there are some sort of changes in the processes for development, and then stress will act on a system that's not typically developed, causing a greater cascade of these problems. So while the HPA is important to stress reactivity, co-occurring anxiety disorders, predisposition to stress disorders that are more prevalent in ADHD, especially the older the child gets and for how or an adult is based on prolonged stress there is rationale for more research into adhd vulnerabilities but not anything that we're saying is causative there are other research routes to inflammation and adhd than just looking at stress and just looking at noradrenaline and dopamine, but some of these bring us back cyclically to dopamine.

15:36So disrupted dopamine signaling in and of itself is one of the things that we look at as a route to inflammation in ADHD. Now there's always the dopamine hypothesis. And again, we don't have consistent findings that dopamine specifically is the cause of adhd but there may be subtle differences in the way dopamine receptors are formed how many dopamine receptors you have how long your dopamine stays in the circuit and that's why dopaminergic drugs are used for treating dopamine. Well, if there are inherent alterations in dopamine signaling, it's important to realize that dopamine is a major signaler throughout the body.

16:27What's being signaled and the way dopamine receptors line up in the brain or in different areas of the brain does not necessarily translate to the way dopamine functions outside of the brain. But dopamine does alter T cell activity and t cells are a major blood cell in innate and in adaptive immunity and so t cells have a very important role in the way we upregulate inflammation or the way chronic inflammation gets shut down um now if we're saying that maybe some people with adhd have inherited difficulties in how their receptors are made, how many receptors they have, or how dopamine cycles, this could theoretically have an influence on the way these immune processes operate.

17:26Again, I'm going to say this is all research and all food for research, but these are reasonable associations that people are looking at and there is evidence in the literature now of t-cell disruptions in people with adhd when researchers have looked um dopamine signals t-cells low dopamine quiets those t-cells and converting t-cells so what one of what t-cells one of the things t-cells does is we upregulate b cells and we convert b cells into antibodies that's the immune memory system so there was a study that found adhd was characterized by more anti-inflammatory t regulatory cells another one showed higher number of t cells is associated with adhd symptoms even without a diagnosis and we know that another thing t cells do is they alter microglia that are directly in the brain and they regulate inflammatory activity in the brain.

18:34Another pathway that's been looked at often in ADHD is that immunoglobulin, it's a protein, altered IgE will dysregulate the way mast cells behave and cause mast cells to release histamine in bursts. And so that's considered a major player in allergic responses. And in ADHD, I know it's been talked about a lot with our friend James Gustau, who talks about mast cell activation syndrome in ADHD. But there are other immunoglobulins like IgM and IgD that specifically associate with autoimmune disease, asthma, and immune weaknesses and those are also dysregulated and occur in higher frequency in people with ADHD.

19:31Another mechanism is that cytokine mechanism that we talked a little bit about before. It's another signaling protein. IL-6 and tumor necrosis factor are often associated with ADHD but they can also measure obesity. IL-6 is upregulated when people are under a lot of stress or have anxiety or depression, asthma, epilepsy, allergies. Some of these things may confound it. So studies have to be really carefully controlled for, but they are sometimes associated with ADHD. There's also an IL-4, IL-13 pathway that's common in ADHD. It's a treatable pathway. There are drugs for it in allergies and asthma and gut problems.

20:20But those things are only usually treated when they co-occur in the context of ADHD and require treatment for allergies, asthma, and gut problems. We don't have research right now beyond the work that Kirshenbaum and their people put out looking at IL-4 on brain activation in ADHD. And IL-4 is dysregulated in ADHD development. And IL-13 isn't treatable. It's part of that pathway that's treatable in allergy, asthma, and gut problems. But the research that we have on that shows that IL-13 effects are mediated by those omega-3 fatty acids and PUFAs. So we look at all of this diverse information and we wonder, can we put this together in something actionable for people with ADHD?

21:18Another pathway to inflammation in the central nervous system is through direct vagus nerve activation. I guess you guys are going to hear more about that next week. But the vagus nerve is a direct route that triggers that anti-inflammatory response through that catecholamine process and it's associated with adhd and microbiome and there are some direct vagal nerve stimulation studies ongoing right now where people again are trying to alter the inflammatory tone through various routes in order to improve functioning and overall well-being and quality of life for people with ADHD. So people with ADHD have inherited one or more of a great many possible vulnerabilities in all of these different biological systems responsible for directing or regulating inflammatory processes.

22:18Now when we talk about people inheriting it we go back to those polygenic risk scores for adhd you know i was told up front you guys are a sophisticated group of people um so i'm sure you're all familiar with what polygenic risk is but uh briefly for anybody who's new uh a lot polygenic means lots of genes um there are lots of genes that add little pieces of risk or a little piece of vulnerability to ADHD. Now, at one point, I took a look at every one of the GWAS genes found on these GWAS genome-wide association studies. I looked at all of these studies and I looked at every single one of the genes that were found on all of the GWAS studies and I put them all into an Excel sheet.

23:17And I found that every one of the genes, all the GWAS studies, they all found genes that were critical for immune functioning. Since 1997 and again in 2015, it was replicated. The human leukocyte antigen DR4 gene, which codes the immune system and it's heritable through family lines, increased risk for ADHD fourfold. In another study or in one of those studies, when that was combined with a gene that codes for complement and complement for is an important component of the immune system where the B cells will present, they'll capture and present pathogens for destruction. When you add that together, the risk for ADHD was 15-fold, meaning that having those aberrant immune system genes, you were that much more likely to have ADHD.

24:26In 2020, genes for coding IL-6, tumor necrosis factor, C-reactive protein, BDNF, all of these immunoinflammatory regulating genes were found on GWAS. Some of these genetic risks are shared across ADHD, autism, bipolar, depression, schizophrenia, and some of these include genes affecting microglia and how reactive oxygen species oxidative stress functions as an immune process. And so some of these are not specific for ADHD, and not everybody will have all of these genes, but having these immune genes means it's more likely that you're going to develop ADHD. But again, going back, ADHD is a neurodevelopmental disorder with polygenic risk, all the subtle vulnerabilities contributing to ADHD.

25:35And we see that presentation can change across the lifespan. But impairments usually persist. And the impairment itself leads to what we call allostatic load in psychology. Allostatic load is cumulative stress. So you've got the vulnerable genes, you've got the cumulative stress, you have a worse stress outcome, which is possibly why ADHD is also associated with neurodegenerative disorders later in life. There was at least one study, population study, showing that ADHD led to a threefold risk for dementia. and another study found that adhd polygenic risk when you do your genome even if you don't have an adhd diagnosis or reported impairment from those adhd from any adhd symptoms that polygenic risk score is associated with greater blood levels of amyloid b and more severe decline amongst people who have dementia later in life.

26:49So you can not have ADHD diagnosis or impairment, but having the genetics associated with that polygenic risk for ADHD increases your risk of dementia problems if you should develop dementia. Those molecular building blocks of ADHD are vulnerable, less resilient, and more prone to those immune inflammatory system failures over a lifespan. So they need to be protected. Now, that kind of begs the question, when does it all start? And when do you want to start to intervene? So some studies look and see where we started and what we're going to look at in the family to see if we can identify kids earlier.

27:41There was a Taiwanese population study. showing that parents that had inflammatory processes increased the child's risk for ADHD. So if parents were diagnosed with an inflammatory disorder, kids were at greater risk of having ADHD. So that kind of gives you an indication. If there's some inflammatory immune issues in the family, maybe keep an eye out and pay more attention to the children. A Danish population study, maternal autoimmune disease did increase child risk of ADHD significantly. Now, you may start to ask, does that mean that the mother's autoimmune disease causes the child's ADHD? But the question was answered pretty well that, no, it doesn't cause the ADHD, right?

28:31So the mothers didn't have to have a flare during the time of pregnancy, but also all other factors associated as risks for child's ADHD didn't really add a whole lot of risk above the polygenic ADHD risk score that the child had. So if the child was genetically vulnerable, then these processes are important. But if the child's not genetically vulnerable, then the risk was minimal. And there was a Japanese clinical study that was a good study and very well done. Perinatal inflammation that was measured by cord blood, right? Because you could say, okay, a mother has these inflammatory disorders, but what's going on at the time she's pregnant?

29:23Is she really inflammatory at that time? and they found that the inflammatory process of the mother in the core blood predicted later ADHD but only among kids who had higher ADHD polygenic risk scores so that risk score that vulnerability is really there particularly again it was tumor necrosis factor alpha and MCP1 which is an indicator of not just COVID exposure and related inflammation, but of any coronavirus and the flu, somebody who's been sick during pregnancy, and IL-6, which mediates fevers and how severe an immune response you have to the illness. And the outcome was done all the way at age eight or nine years old.

30:17So you can see how this is a longer developed process. Lots of health risks are associated with ADHD, and I'm going to skip that pretty quickly because I'm going to want to get on to some important features that I want to discuss with you. If you are a person who's really concerned, we've established there is a connection between ADHD and inflammatory disorders, but it's important to realize that they're not all inflammatory disorder related brain fog or inattention is necessarily ADHD either. So you can have ADHD with brain fog from inflammatory disorders. You can have no ADHD and brain fog associated with inflammatory disorders or stress and inflammatory disorders, or you can have both at the same time.

31:13And that's important for you. And why is it important for you? Because if you're having new onset brain fog, that's something that you really need to sit down and talk to your doctor about. We've done studies here in children and in adults where we've looked at the cognitive profiles of people with something called sluggish cognitive tempo, which is now called cognitive disengagement syndrome, which occurs in 60 % of people with ADHD, but also occurs without ADHD. And there are distinct cognitive profiles of attention that are affected in ADHD versus this kind of cognitive brain fog. And people with ADHD and the cognitive brain fog, the attention profile, we disassociated the two and we were able to find differences.

32:12But it's something that we did experimentally, doing very careful neuropsychological phenotyping. And it can be difficult because that's not part of a common neuropsych battery in clinical care. SCT and CDS, that sluggish cognitive tempo, is associated with more oxidative stress, more inflammation, more anxiety, more mood disorders in context of ADHD. Now, the STT construct is something that was separated out from ADHD when they put together the diagnostic symptoms for ADHD because it's a cluster that hangs separately. So this concentration deficit disorder, it's trait-like symptom dimension, daytime sleepiness, dreaminess, fog, confusion, slowed cognition versus the neurodevelopmental disorder that is ADHD.

33:13there's also a separate construct when we're talking about physical health problems called cytokine mediated sickness behavior which is a very well identified construct that is a state dependent response to immune activation and it's short-lived so how do you figure out whether you've got sluggish cognitive tempo adhd or cytokine mediated sickness disorder when you can have all of these and they may be mechanistically different but when you have an illness that onsets and you have a sudden influx in symptoms it's more likely to be a cytokine mediated sickness behavior. ADHD is more of a stable more trait-like set of difficulties with appropriate regulation of attention and concentration um and sluggish cognitive tempo has more of these kind of sleepy daydreamy fobby sorts of responses that do separate out we have separate scales for adhd and sluggish cognitive tempo um but biologically we see that tnfa and il-6 have something to do with both cytokine mediated sickness behavior but also with adhd suggesting that there is some sort of global inflammatory process cytokine mediated sickness behavior has been reviewed on mri and they say see an early basal ganglia, dopamine suppression, and later HPA access, tryptophan, chyanurine pathway issues, which is different than what we see on MRI for ADHD.

35:09So some of these blood markers may not be the best way of determining whether it's cytokine mediated or ADHD. um the helpfulness of this is that there really aren't any fda approved adhd medications right now that are well um well reviewed for their effect on these anti-inflammatory processes but there are some studies now that are starting to look at what can be used to look at these immune profiles and since there's nothing currently approved what does this mean for care when possible always identify and treat those underlying conditions because if they're contributing to your inattention and brain fog and overall poor quality of life not treating them can cause some of those adhd symptoms and some of those impairments to look worse if you're treating that underlying condition you can improve your overall functioning and it will be easier to manage your adhd too monitor how cognitive and physical symptoms change in relation to each other and in relation to treatment to give you an idea of what's moving and what you're treating.

36:40And, you know, we say that an anti-inflammatory lifestyle can improve well-being, but it's not a cure. And I'm a big proponent of not spending a lot of money on something that's not proven to work for you. And it's not just money. It's also really, really difficult to maintain a rigorous anti-inflammatory lifestyle the way some of these wellness people will tell you you have to and that can lead to a whole cycle of trying to implement something not being able to implement it feeling ashamed for not having implemented and spiraling and so I'm a big believer in being kind to yourself and limiting that kind of negative self-feedback.

37:30Choose a clinician. You can hold uncertainty. It's very difficult to find a good clinician. Find one who listens to you with respect, starts with your goals, reflects back your story, reviews evidence you provide, and takes function and safety seriously. Remains curious and can distinguish unlikely from unknown and give you a good hypothesis for what they think is going on, but is willing to remain informed, research and collaborate with specialists, document a rationale, define red flags and set up a follow-up. They should be able to answer you if you ask them, what's your leading hypothesis on what's causing this?

38:12What would change your mind about it if I I gave you more information. How do we know my plan is working? And they build a good partnership with you. Monitor your health. Choose a few symptoms. One is enough and start going with that. Capture it. Put it into a record where you're contextualizing it by recording your sleep. What makes that symptom better or worse? Review it and then try to act on it. decide who you're going to contact to try to help you monitor it and treat it if it becomes something that you need to treat. And try to bring a one-page checklist with you to the appointment because when you get into the appointment, it can be really easy to forget what you were going to talk about.

39:01You're not trying to self-diagnose or prove a theory. You're just trying to help the clinicians see a pattern and what that severity of the issue is, how it's affecting you and what the risk may be to your well-being. So they can guide you to select your next steps. You know, bring your top one to three concerns and priority order and how you've mapped those symptoms out. Bring your medication lists and be truthful about any supplements you're taking, caffeine, nicotine, alcohol, cannabis, CBD, whatever. Record your sleep, your pain, your fever, rashes, joint pains, bowel movements, weight changes, whatever those somatic problems are.

39:48And when you leave, leave with your record, your blood pressure, your pulse, your weight, whatever is relevant information and records so that you have that to share with the next provider that you're going to be talking to, whether it's a specialist, and try to get a written next step plan so that you know how to follow up. Don't wait for a routine appointment and get emergency care if something is severe, if there's chest pain, you're not breathing, you're fainting, or there's something new. Anything that triggers an emergency, go right away and have them contact position. Exercise has the highest yield for overall well-being, you know, but you've got to make it something that you enjoy and can do and that you're not overdoing and causing stress induced injuries.

40:42And you have to be mindful about what underlying conditions you have so that you don't exacerbate any problems. Progress without perfection is what you're looking for if you have a lot of inflammatory issues. Sleep problems. If you can sleep well, it will reduce your overall interleukin and CRP inflammation levels. And that's good for anybody with or without ADHD, but you need to build a toolkit of relaxation strategies and try to keep a regular schedule in order to maintain your sleep hygiene. Cognitive behavioral therapy for insomnia protocols are helpful, and there are psychologists who can implement those with you and adapt those for ADHD.

41:32When it comes to diet, people always ask if there is any good evidence for an ADHD-specific recommended diet, and there isn't. If you have food allergies or intolerances, if you have co-occurring celiac or if you have alpha-gal and just can't eat meat whatever it is that you may have as your underlying biological reason for looking for a specific diet treat that as if it is the health issue the adhd piece of it comes into how well you're able to keep to it how well You can read your allergy labels, you know, and just generally try to be healthy and maintain a good diet. Try to buy pre-cut vegetables or meal kits if that's what's going to help you.

42:26Looking for fewer processed things and overall nutritionally rich foods. Supplements are used for correcting deficits. It is possible to overdose on them. So if you don't have a deficit, you don't necessarily need to be taking a supplement. And you should be mindful that whatever you're taking doesn't interact with your medications. Talk to a provider. Don't overdose on them. There's not enough evidence to really support recommending anything as an ADHD-specific improvement. A lot of people take omega-3s or vitamin D, but again, that's something that's very individual and not a global recommendation.

43:17so in summary unhealthy inflammation with or without adhd is a problem inflammation can be protective dysregulated inflammation can produce cognitive and behavioral phenotypes of inattention with or without adhd people with adhd and sct cdms or cms usually have more severe symptoms of both ADHD and health problems. It can help to understand whether symptoms represent core ADHD symptoms or other phenotypes when tracking treatment for ADHD, because sometimes your medicine may really be working on your ADHD symptoms, but not inflammatory symptoms that are occurring for SCT. And so you need to know what's causing your inattention and how well your treatments are working.

44:11There's a need to identify and treat any underlying or co-occurring diagnosis for your own well-being and longevity. Genetic studies show risks for inflammatory conditions associated with ADHD and symptoms. Dopamine and catecholamine noradrenergic signaling directly regulate immune inflammatory activity, but it's not clear if medications for ADHD do help with those inflammatory conditions. Data is pretty clear that people treated for their ADHD live longer, healthier lives on average. So getting treatment does matter and maintaining your health can be more complicated in context of ADHD and how the ADHD affects your health-related behaviors.

45:02um i think i may be at the end of my slides thank you so much dr crone for such an important and comprehensive presentation and thank you for translating the science for us um i'd like to share answers to our poll question we asked if you have adhd have you also been diagnosed with or suspect that you have an autoimmune related disorder, here's what you said. Gut problems were among the most cited, followed by skin and food allergies, asthma, and hypermobility. Now to your questions. Could perimenopause or menopause cause or exacerbate any of these inflammatory conditions? So perimenopause and menopause estrogen changes are very well known to influence the immune system.

46:04In some disorders, they make things better. So estradiol can be inflammatory estrogen fluctuations. A lot of people with lupus go into remission when they hit menopause or perimenopause because once the estrogen levels go down, the inflammation from the lupus starts to subside. But in other disorders like MS, it can upregulate. Some of those neurodevelopmental disorders can upregulate um so yes perimenopause and menopause definitely influence um these disorders and how that interacts with adhd is more complex than just saying menopause to inflammation but it matters on the specific route and the pathway that your body is going through.

47:08So you need a really good doctor in the end who can diagnose you and treat you well. Okay. Someone asked, with altered T cell activity in ADHD, does that predispose people to autoimmune disorders? so the predisposition to autoimmune disorders um it and again it depends on the autoimmune disorder um the predisposition is usually heritable and not completely identified. What we're talking about with T-cells is, you know, a possible co-occurring pathway. So if you inherit a signaling problem, it's not necessarily the same as not having the right number of T cells. If you have a receptor problem, that's something different.

48:19So I wouldn't say that you're predisposed to autoimmune disease because you have ADHD. I think that you have more ADHD in people with autoimmune disease. Okay. um someone writes she drinks alcohol before bed sometimes and smokes marijuana or does edibles um and she's wondering if that if any kind of substance use that she says is moderate would somehow cause or heighten inflammation in the short or long term. Do we know? Do we have any information on that? So the research on CBD, you know, and I just from talking to people who work in the field on cannabis, um very smart people like john markowitz and and um you know talking to me about the pharmacology of it you know is it inflammatory is it anti-inflammatory it depends on thc to cbd ratios and you know what strain it is and again it's gonna require sitting down with somebody to talk about it, who knows what you're doing and what your biology is and sitting with a clinician.

50:01What I will tell you is that overall in the field, we know that cannabis does not make ADHD symptoms better.

50:15It doesn't help. It can make ADHD and attention in your cognition worse. Alcohol, and again, it depends on the kind of alcohol. There's a lot of research into red wine and anti-inflammatory properties associated with red wine. But then there's other research on beer being harmful and being inflammatory. And again, you're going to have to sit down and talk to somebody. the idea of taking even moderate substances before bed, you know, it is not necessarily the best sleep hygiene. Okay. Could the anti-inflammatory benefits of GLP-1s affect ADHD symptoms and or autoimmune disorders? so that's something that we really want to find out um you know there's been some research lately on it and a lot of us who are working with people with adhd are interested because everybody's interested in glp ones right now they do have effects on the brain in regions that are critical for ADHD.

51:35There was a really good review written by Nora Volkow that was published talking about reward. She's focusing mainly on substance abuse, but these are all regions of the brain that we've looked at in ADHD, and they are critical in ADHD and decision-making and cognition. So there's hope there, at least for certain kinds of autoimmune diseases. There's hope there. Okay. Could transgenerational trauma increase the possibility of the kinds of genetic changes to genes that are related in these studies? That would be another great thing to look at yeah these are fantastic research hypotheses they're awesome um you know there's a lot to be controlled for in transgenerational trauma whether it's behaviors or you know relational issues or epigenetics or what it is um looking at it and then seeing if that has an epigenetic effect could be interesting.

52:52Right now, GWAS studies are not looking to my knowledge. Well, I mean, they can, but they're not looking specifically to my knowledge at epigenetic effects yet. I think they're looking more at some of these non-coding regions and some more of that may come out. and I'm looking forward to that happening. Yeah. Is there anything that can be done to reverse inflammation? Oh, well, one thing is treating the underlying disorder if you're diagnosed with it and that's really important to do because the types of treatments differ between disorders because the different disorders have different mechanisms.

53:40So if you're on an asthma medication, maybe it is an IL-4, IL-13 pathway medication. If it's, you know, it might be a biologic, it might be a disease modifying drug that like a Plaquenil situation. There are different methods of tapping the immune system to down-regulate inflammation. So if you have a disorder, getting it diagnosed and properly treated is the first step. If you are having difficulties and they're more diffuse, you know, stress management, sleeping, eating right, exercise, generally living a healthy lifestyle is usually the recommendation for most people. Okay. Someone says, my husband and I have a 53-year-old son who has early onset Parkinson's.

54:41I'm wondering if his ADHD plays a part in his having Parkinson's, and especially at such a young age. Oh, I'm sorry to hear that. um parkinson's is associated with adhd we don't have right now a direct link between the two um you know people want to say that there's a link because it's dopamine function but it's in an area of the brain not associated necessarily with adhd um i did a review recently with one of our colleagues because we were looking at potential links through neuromelanin and other mechanisms but we weren't able to find a definitive link that's where the research right now in adhd and parkinson's seems to be going they're looking at neuromelanin as a connecting process um the acute because when dopamine breaks down in the brain it produces neuromelanin which is sequestered in cells and the dopamine cells um and damage to the cells or too much of the neuromelanin kills the dopamine cells and that is a mechanism in parkinson's and because that's dopamine related people are trying to relate it to adhd but there's not good scientific research on that right now.

56:17Okay. It's really interesting area of research. Yeah. Someone asked, do certain autoimmune conditions show up at certain ages? It's pretty broad. I do. Yeah. Some things are more common in children like, you know, type one diabetes. Right. More likely get it as a child. Other autoimmune diseases. You know, I've talked to dozens of rheumatologists who will tell you, oh, that's more of an older thing, a midlife thing. look at me you know 20s 30s 40s and yet you know I've met many mothers who sat down and said I know my child has this and then forced a doctor to do the testing and the testing's come back positive I've known children with rheumatoid arthritis you know in elementary school so more likely sure maybe but maybe because we don't always look for the signs in little kids unless things are super severe yeah um the last question does red light therapy help with inflammation as is claimed um i honestly haven't read the research on red light therapy uh well enough to make an informed answer.

57:46My suspicion is probably it's not as useful because I don't know any physicians who are recommending it, but it's not something that I'm very familiar with. Okay, fair enough. Well, Dr. Krohn, thank you so much for sharing your research and expertise with our ADHD community. we appreciate you. I appreciate you. Thank you so much for having me. I hope it was helpful. Yes, thank you for helping us to make sense of this. It's very complex. When you talk about genes, it's great. It's just, it's hard to understand. So we thank you for that. And to our viewers, if your question wasn't answered during the webinar, we do share audience questions with our experts and yours may appear in a future edition of Attitude Magazine's Ask the Advisor column.

58:45If you would like to access today's event resources, visit attitudemag.com and search for Podcast 620. The slides and recording are posted a few hours after each live webinar. If you're listening in replay mode, simply click on the episode description and please know that our full library of Attitude webinars is available as a podcast It's called the ADHD Experts Podcast, and it's available on most streaming platforms. Get alerts for future Attitude webinars by signing up at attitudemag.com slash newsletters. Thank you, everyone. For more Attitude Podcasts and information on living well with attention deficit, visit attitudemag.com.

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