ADHD and Obesity

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Okay, so we will get started and the session is being recorded and will be shared with everybody following the session. So hopefully if anybody joins us late, they can catch up at a time that's convenient. So we have a fantastic webinar for you today, all about ADHD and obesity.

So we have two colleagues from Time Spam that are going to be presenting for us. What I'm going to do is drop their speaker bios into the chat so you can have a read of those and we can get straight into the presentation. So first of all, I'm going to pass over to psychiatrist, Tony.

So if you'd like to take the floor, Tony, and share your slides. And if anybody has any questions for either of the speakers, if you can just use the chat function throughout the webinar, and then we'll pick those at the end of the presentations. So yeah, anything that comes to your mind as we're going through, just pop them in the chat and we'll make sure that hopefully we can get through them all at the end.

So thank you very much, Tony, the floor is yours. Thank you, Cathy. Well, first of all, thank you so much for this opportunity for the Consortium Time Spam to be here with all of you and present some of the general aspects related with ADHD in my case, and later on with Professor Henry Larson, presented more specific aspects of obesity and ADHD.

My name is Tony Ramos-Quiroga, I am Professor of Psychiatry, working with my friend and ASU Dean in the Valdebaran Hospital here in Barcelona, and also the Autonomous University of Barcelona, and member of the Time Spam Consortium. My talk will be around a quick look about ADHD and with this perspective across lifespan. That is my potential conflicts of interest with several companies or other associations or other institutions.

Well, first of all, I would like to introduce this perspective of ADHD as non-precisely, as you can see here, non-precisely new disorder. ADHD starts the history of the disorder with Adam Baker in the end of the 18th century, and was described at the Lancet paper by George Steele, the pediatrician, that defined it also the still illness or the still disorder, this picture of symptoms of ADHD. And also, it's absolutely interesting to know that, in fact, the first psycho drug that was tested was an amphetamine, the benzidrine, and was in the middle of, in the mid-30s, and was in a clinical trial tested with children with ADHD.

And methylphenidate, one of the drugs more used around the world, is a drug not also precisely very new drug, it's a drug at the end of the 50s, and the first studies taking advantage of all of the continuity for ADHD, and having more clinical pictures and data of adults with ADHD is at the end of the 60s. Now, we have a tremendous advance in the field of ADHD, attention deficit hyperactivity disorder in terms of genetic, neuroimaging, and database register that later on, I'm sure Henry Larson will present. ADHD, in fact, is a neurodevelopment disorder, a spectrum disorder, autism, or Tourette's syndrome, or dyslexia.

It's a disorder that affects also males, females, different cultures, it's not a Western disorder in this term, but also a disorder that clearly starts during the childhood, and can persist across lifespan, and also could affect the elderly. Here, in a quick look, you can see here that more than 60% of the variants related with ADHD, it's explained by genetic factors, in fact, is one of the most genetic mental health disorders together with autism and schizophrenia. But also, there are actually 4% of the risk factors or the factors associated with ADHD that are environmental factors.

One of the importance of ADHD is the high prevalence in the general population. As you can see here, around 6% of the children have ADHD, and clearly in adulthood, this disorder can persist in more than 50% of the people. One of the explanations why we have this difference is that not all the children with ADHD will be adults with ADHD.

But also, it's important to know this perspective. This slide is one of the most important related with ADHD, because here, we can have a clear perspective of a disorder that starts during the childhood, and with this perspective across lifespan, all the different issues and burdens related in each of these steps, but also, I think it's important to know that we have the possibility to introduce with this mental health disorder with ADHD, a secondary prevention, because if we treat correctly with the diagnosis correctly ADHD in childhood, or also in adolescence, or later on during the adulthood, for the first time, we can change this perspective of negative impact and the burden for the population. During the childhood, obviously, one of the most impacting factors are all the academic performance, but for us also, it's very important, this aspect of the poor self-esteem, because this poor self-esteem will be a clear risk factor for more problems, more issues during the adolescence.

For example, the substance use disorders, or legal problems, or also injuries with other aspects. Here, I would like to introduce also the aspect that later on Henry Larkson will treat in a deeper way, that obesity is clearly related with ADHD. ADHD is a risk factor for developing obesity from the early adolescence in these children, but also during the childhood.

It's not very well-known, this important paper published in 2015, in Lancet by the group of Dalsgaard in Denmark, that ADHD increases dramatically the mortality risk, relative mortality risk, in people affected with ADHD, but ADHD also, it's very common to have other comorbidities. Like OCD or conduct disorders, or also to have these issues of substance use disorder. When we have more comorbidities, and it's very common, 40% of the children with ADHD across lifespan will develop substance use disorder.

In these cases, the mortality risk increases dramatically, up to eight times the general population. Also, in this case, with ADHD and mortality risk, it's important to remember that also there are gender perspectives, very clearly, because females have more risk of mortality than the males. And maybe one of these explanations is because the first diagnosis of ADHD for females are later on during the adulthood, and not at the very beginning of the childhood.

That is a clear bias. As I said before, ADHD is a very clear genetic disorder, with a clear genetic basis. That was the first GWAS with positive results, with more than 50,000 people involved.

In this case, we found 12 positive losses related with ADHD. And also, this biological profile affected with, can be affected with ADHD. One of these, this year, GWAS with more and more people included, and we found more losses related with ADHD.

Early, when we will arrive to 100,000 subjects, we will have hundreds of losses related with schizophrenia or bipolar disorder. Also, as I said before, not all the children with ADHD will be adults with ADHD. And in this case, it's a study that we performed in Barcelona in our lab by Paula Rovira, one of my PhDs.

And in this case, we compared what is the correlation, the genetic correlation with children and adults with ADHD. And we clearly found that more than 80% of the genetic correlation between children and adults with ADHD. That is in a way to validate this perspective of a disorder that can continue during the adulthood.

Nowadays, we have a set of guidelines, the NICE guidelines for the diagnosis and the management of ADHD across life span. And here, for example, also the Spanish guidelines, there are the Canadian guidelines, German guidelines, et cetera. And also, we have a consensus of the European Psychiatric Association about the diagnosis and the treatment specifically for adults with ADHD.

And also, we have a consensus of the European Psychiatric Association about the diagnosis and the treatment specifically for adults with ADHD. And also, we have a consensus of the European Psychiatric Association about the diagnosis and the treatment specifically for adults with ADHD. them, that we can have the possibility with a good diagnosis and a good treatment to prevent secondary aspects or as I like to say, these nefastacies associated with ADHD like obesity or like criminality or like substance use disorder.

One of the most common symptoms obviously for ADHD is the set cluster of inattention and symptoms and also the cluster of hyperactivity impulsivity. This cluster of symptoms are the core symptoms of ADHD and are the symptoms that we can differentiate in a good specificity with other disorders as bipolar disorder or depression disorder or schizophrenia for example or autism spectrum disorder. But also ADHD runs with emotional ability or emotional dysregulation.

It's not a core symptom by definition of ADHD, but are very common these set of symptoms that later on we can discuss. And also motivational deficit with this impact on the functioning of the dopaminergic system. As you know, dopaminergic system is essential for you to have a good motivation and in case of ADHD, there are alterations, modifications of this dopaminergic reverse system on the brain and that affect the symptoms of motivational deficit.

Also very common with ADHD. Well the criteria included on the DSM-5 are very clear. We need this set of symptoms for children.

We need to have six of the nine symptoms that describes inattentive symptoms or and six of nine of hyperactivity impulsivity symptoms. For adults, it's not necessary to have these six, five is enough to have burden, to have dysfunction and negative impact. Also, it's very important to pay attention to the B criteria because that criteria can increase the specificity of the diagnosis because if we need to have the first symptoms of ADHD before adolescence, before 12 years old, and with this criteria, we increase dramatically the specificity of our diagnosis.

Also, it's absolutely important to have impairment. If we don't have impairment in different settings, two or more, that also these two criteria together with B criteria increase dramatically the specificity and also obviously is not better explained for other disorders. But with the first four criteria, we can get a very specific and very precise diagnosis of ADHD.

Here is the typical nine symptoms included on the DSM-5 for inattentive symptoms. As I said before, it's necessary to have six of these nine for children for having criteria of inattentive symptoms or five of these nine for adults. And remember, it's not only the idea that to have a person with forgetfulness or a person with difficulty sustaining attention in tasks, we need to have this set of symptoms.

The very typical profile for adults, for example, with ADHD are those without a lot of problems, a lot of problems for managing with the calendar, to procrastinate tasks, to be very, very, very, very easy to have mistakes doing tasks, for not paying attention, to lose things and pass a lot of time during the day trying to find the things. Yes. And also this difficulty to sustain attention in tasks.

That is the typical profile. And also could be together or separate this cluster of symptoms of hyperactivity, impulsivity. In red color, you have the symptoms of impulsivity and in black color is the symptoms of hyperactivity.

It's quite common to include together these nine symptoms and to screen if we have more of six or five for adults of these symptoms. If we have more of these six symptoms or five, we can say that this specific person has criteria for hyperactivity or impulsivity. The typical idea is a person that, for example, for adults being very talkative with a lot of problems for waiting, waiting in turn or, for example, to respond to questions before the others can finish to talk, to interrupt to others.

And these two symptoms that we have, this red circle, is because these are the definition for children. But in adults, it's not common to clean, for example, on the tables or at the tables or moving constantly during the room. That is not the case.

For adults, the symptoms are this readiness, this idea that I never stop to do activities. I need to be engaged in activities all the time. But the rest of the symptoms are very similar between children and adults.

With this combination of inattentive symptoms and hyperactivity impulsivity symptoms, we have the three different presentations of ADHD. The most common is to have both together inattentive symptoms and hyperactivity impulsivity. Around 60 to 70 percent of the patients have this presentation.

The other, the second more common, is to have only inattentive symptoms with few symptoms of hyperactivity. We shall take a top of five or six or more. And in these cases, the inattentive presentation is around 20 percent, 30 percent, it depends on the samples.

And finally, the most uncommon is only the hyperactivity impulsivity, only around 5 percent, no more than 10 percent of the samples. Well, as I said before, this emotional ability or emotional dysregulation are very common in adults and also children with ADHD, with symptoms of irritability or symptoms of predictable mood or sitting off easily or hot temper, low frustration, tolerance and also difficulty in anger management. All of these symptoms are very common on ADHD, but are not included on the core symptoms by definition of ADHD.

These symptoms are very common also in bipolar disorder, in people with bulimia nervosa or people with substance use disorder, or also in some patients with depression or anxiety. These are very specific symptoms, but very common and also symptoms that impact very negatively on the life of persons having a high burden. The diagnosis of ADHD and the other mental health conditions are essentially a clinical interview.

We don't have at the moment biomarkers, and for that is essential to have a good assessment, a good clinical interview. And the most practical tips is to go retrospectively if we are in front of an adult and to take and to review if during the childhood they have symptoms of ADHD, because it's a disorder that starts during childhood and have this neurodevelopment perspective. It's a chronic disorder.

It's not a disorder with relapses, with phases as a bipolar disorder, for example. We need to have, obviously, by definition, the number of symptoms in the case of adults with ADHD, five or four children, six or more of these symptoms. And we have this idea if without clinical impairment, it's not a disorder, it's not the idea of disorder, it could be a subvariant of the normality.

But for ADHD, we need to have an impairment. With all of these characteristics, we decrease dramatically the false positives diagnosis, and it's absolutely essential to have a very careful diagnosis in this case. Also, we have some instruments, psychometric instruments, that could be very useful to have a right diagnosis.

These instruments are used on the clinical settings, but also for research. We introduce a semi-structured interview, self-reported scales for the assessment of the severity of ADHD, or also the observer scales, scales that could be for the family. And neuropsychological tests are not critical in terms of the diagnosis, but could be very helpful in terms to have a more precise profile of the negative impact or the burden that this person can have.

For interviews, I clearly recommend you the DIVA. In this case, there are the DIVA1, it's not the DIVA2, it's the DIVA5, or the Connors for Adult ADHD, the KD, or the ACE+. There are the three most well-used interviews for the diagnosis of ADHD for adults.

And also, if you are inferring an adult with a substance use disorder, it could be possible to use the psychiatry research interview for substance use disorder and mental disorders, the PRINCE, and it's a good semi-structured interview for differentiating if someone has an ADHD or these symptoms of ADHD are only related with cocaine addiction or other. And the FAST interview is a good interview for the assessment of the functionality. It's an interview that is only necessary five, ten minutes is enough.

And you can have a clear picture what is the dysfunctional level of ADHD. This is the DIVA5, and you can go to the DIVA website or the DIVA Foundation that we developed with Sandra Koich. And this interview is available in a lot of languages.

And also, we have validation of these interviews. For the scales, I could recommend you the Wendell Utero Rating Scale. It's for free, available by Internet.

And it's on a scale that you can assess retrospectively in adults what symptoms they have they had during the childhood. The other is the ADHD Rating Scale, it's a typical scale for the assessment of symptoms during the adulthood or the adult cerebral scale that is very useful for you, for example, for a skin, if an adult can have ADHD with only four or five minutes is enough for this screening. And also another scale that is necessary, the SSRS is available for free and also the ADHD Rating Scale, but the Conexal Rating Scale, it's necessary to pay fees for this scale.

And the Wendell Rating Scale disorder also is a scale for the assessment of the severities during the adulthood. This is the SSRS, it's only very simple, it's a Western scale developed by the World Health Organization. And as you can see here in this area with X, if someone have four or more X in this area will be suggestive of having an ADHD.

And it's very simple, you know, five minutes is enough and you can screen very well if someone can have an ADHD. If the patient had a negative score, a negative result, the sensibility is very, very high. And if the patient have a positive score, we need to continue with more assessment to do, for example, one of these semi-structured interviews.

ADHD is very, very common in other disorders. We know clearly that 12% of patients with major depression also has ADHD or 15% of the patients with anxiety or 10% of patients with bipolar disorder is very, very common with autism spectrum disorder. 25% of people with the spectrum also have ADHD or with borderline personality disorder or finally with eating disorder.

In this case, it's very common for bulimia nervosa, around 21%. And when ADHD is together with all these other disorders, the typical profile is that these disorders are with high severity and also very common to have together to ADHD. And in this case, with bulimia or with bipolar disorder, you have to get a substantive disorder.

And for that, we said that ADHD is a high-risk disorder because it's very common to diagnose properly the substantive disorder, anxiety, depression. In this case, adult psychiatrists have more experience with this disorder. But for the majority, for these patients, in around 15% of these patients also, they have ADHD.

And if we don't treat ADHD, we increase the negative outcomes of depression and anxiety. It's absolutely essential to treat together these disorders. The good news is that we have very good treatments for ADHD across lifespan for children, adolescents and also for adults.

We have a pharmacological treatment. The most efficacy and the most used are stimulants, methylphenidate, or amphetamines. There are dopaminergic drugs and other neurodegenerative drugs.

And also known as stimulants, like tamoxetine or other neurodegenerative drugs. There are other non-sensitive drugs, like bupropion, that could be useful for patients with ADHD. And in terms of psychological treatment, the most well studied is the cognitive behavioral treatment and also the mindfulness treatment.

In global, the response is around 80% of the patients with ADHD have a very good response to this combination of drug treatment and psychological treatment. One of the challenges with ADHD is the continuity of treatment. This is a paper published a few years ago, and here is a paper published in the United Kingdom.

As you can see here, all the adolescents here start with 16 years old at the very beginning, the baseline, 100% of them were under pharmacological treatment. But in only two years, more than 50% of these patients stopped the treatment with very bad adherence. And that is a challenge that we have to understand better why patients don't have good adherence and to know more about the long perspective of the long term use of the drugs that we are testing for ADHD.

For that, we ran this exciting project, TimeSpan. And in the TimeSpan, the WorkPacket 5, we included a clinical trial, the R-Karma, it's named ADHD Remote Technology Study of Cardiometabolic Risk Factors and Medication Adherence. And in this R-Karma study, we will recruit 300 adults.

It's led by Johanna Kunze in the King's College London, and 150 will be included in Barcelona in Bidebron Hospital. We will use passive monitoring with wearable devices, Embrace Plus, and also a passive app. And we want to monitor during one year the cognitive tasks, questionnaires by apps, also the speed, task, weight, and the blood pressure.

And we will take advantage of all of this radar base that was developed for previous European grants. And with this passive monitoring, we will have a long set of variables, respiration, sleep, skin temperature, as you can see here on the slide. And also every month and every week, we will take the assessment of the psychopathology and also the use or not, the secondary, the side effects with the drug.

And at the end of these 12 months, we would like you to understand better why are the factors related with non-adherence and also what is the predictive aspect regarding the cardiometabolic factors. That is the list of the people involved in this World Packet 5 and in this clinical trial with R. Karmann, as I said before by Johanna Kunze. Well, a summary at the end, ADHD is an irrelevant disorder with chronic impact, with high genetic background, ADHD in adulthood also.

And there are some instructor interviews and with the scales for the diagnosis. We have guidelines and consensus for adults in order to have a good treatment. And also, as I said before, ADHD runs with high comorbidity with other disorders.

And one of these disorders, as we will see now, is obesity. Thank you so much for all the team in Vitebron that are working in this project and all the colleagues of TimeSpan. Thank you.

Fantastic. Thank you, Tony, for a fabulous presentation. And we can either do questions now if you prefer, or we can save them or undo them at the end.

I haven't had any through. Or just have one from Luca. I don't know if you want to take that now, Tony, or you want to save it to the end.

It's up to you. Sorry, if you want, we can manage all the questions at the end in an open debate if you prefer. Yes.

And you have more and more flow with the presentation. OK, perfect. So we'll pass over to Henrik now.

Henrik, if you'd like to share your screen and take the floor, that would be fantastic. Henrik is a professor in epidemiology based in Sweden, and he is going to present to us now. Thank you very much.

Sorry, some technical issues. I had to unmute before I shared the screen, otherwise it was difficult. I will continue now.

Can you see the screen OK? Can you hear me OK, too? Yeah, perfect. Thank you. Perfect.

Thank you very much for the introduction. Thank you very much for inviting me. This is very exciting for me and for the project time span to be here and talk about ADHD in general.

You just heard Tony's excellent presentation. I will dig into more details around research around causes and consequences of obesity in ADHD. So initially, I thought I would focus primarily on studies that we have conducted in Sweden on this topic, but I decided to broaden the picture a little bit so I will not only talk about registered based studies from Sweden, but provide a more general picture about this topic.

I hope that is OK. So I am the scientific coordinator of TimeSpan. I would like to start off and present my conflict of interest and ongoing grants and then spend just a few slides introducing what TimeSpan is about.

So TimeSpan is a European project, a Horizon 2020 project. The focus is on the management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients. TimeSpan involves or includes 17 partners across the world, and I have highlighted EASO here.

They are a former partner of TimeSpan and we work together with them in this project, which is super exciting. I think it's appropriate to ask why. Why did we decide to study adult ADHD and cardiometabolic disease? There could be long and complex answers around that.

I would provide a simple and quite straightforward answer to that question. As I think was clear from Tony's presentation, it is well established that ADHD often co-occurs with other psychiatric conditions. That means psychiatric comorbidity is high and it's well known and well established.

As a consequence of that, as a consequence of that knowledge, there are clinical guidelines available to help mental health teams to handle and treat ADHD when it comes together with other psychiatric conditions. Well, now research indicates that there are associations between ADHD and different types of cardiometabolic disease. That is, individuals with ADHD are at increased risk of cardiovascular disease, type 2 diabetes, as well as obesity, as I will talk more in detail about.

But there are still a lack, a clear lack of treatment guidelines about how we should manage and handle cardiometabolic disease in those with ADHD and vice versa. This is a critical goal of time spent to build knowledge around this and eventually we are aiming towards informing clinical guidelines about how to handle ADHD when it comes in context with cardiometabolic disease. This is roughly what I will talk about today.

So I will talk about causes of obesity in ADHD as well as consequences of obesity in ADHD. And what do I briefly mean with that? So when I talk about causes of obesity in ADHD, I will discuss and present research findings about the overlap between ADHD and obesity and the prevalence of obesity in ADHD. I will talk a little bit about the directionality.

Is it ADHD that is a risk factor for obesity or vice versa? And then I will touch upon different aspects, different potential explanations to why we see an overlap between ADHD and obesity. I will end up the talk with discussing consequences of obesity in ADHD. And this is really the main focus of time span, but more broadly around cardiometabolic disease.

Here we really want to understand how we can better help and manage people with ADHD and co-occurring obesity to help improve prognosis, outcomes and treatment. OK. So here with this slide, I want to start off by taking a small step back and say that overall, not only specifically in relation to ADHD, but more generally in psychiatry, there is a huge interest towards achieving a better understanding of why mental and physical conditions overlap.

We recently conducted an umbrella review. An umbrella review is sort of a review of all available meta-analysis that exists. We conducted such an umbrella review recently.

And what you can see here is that one of the evidences that emerged from this umbrella review was that ADHD is associated with obesity. And what I want to highlight is that obesity is actually the most studied physical slash somatic condition in context of ADHD. So it's a well-studied phenomenon.

It has been studied for the past 10, 15 years and we know quite a lot. What you see on this slide is probably the most comprehensive meta-analysis exploring the association between ADHD and obesity. This study was included in the umbrella review that I've just talked about.

But here I want to go a bit more into detail what this most comprehensive meta-analysis actually demonstrated or showed. So first of all, I just want to provide some details around how this systematic review and meta-analysis defined obesity. So for adults, obesity was defined as BMI of 30 or above.

Obesity in children was defined as a BMI score about the 95th percentile, stratified for age and sex. This comprehensive review identified in total 42 studies that have explored association between ADHD and obesity. It included over 700,000 participants, including almost 50,000 individuals with ADHD and almost 700,000 controls.

This is a very busy slide, I know. So this is actually a slide that presents all relative risks that was presented in each of the included studies. And at the bottom of this slide, you see the overall estimate where you combine the relative risk across all these studies.

So the main finding of this systematic review and meta-analysis was that ADHD is associated with a 1.3% increased risk of obesity. So what does that mean? It means that the risk is 30% higher in individuals with ADHD compared to those without ADHD. If I should elaborate a little bit further, if we say that the prevalence of obesity is 10% in the general population, the prevalence of obesity would be 13% in those with ADHD.

This is what this relative risk means. Another interesting finding from this meta-analysis and systematic review was that they presented results separately for children and adults, as you can see in this table. The take-home message here is that if we look at the statistical significance, we see that age did not differentiate the risk.

So overall, there is a similar risk in children as well as in adults. I should say that, as you can see, if you look at the column with odds ratios, you can see that the odds ratios are slightly higher among adults compared to children. But there were not enough studies to say with precision that the risk is higher among adults compared to children.

So more research is needed on that to explore whether there are differences across age. If we elaborate a little bit more around the results separately for adults and children, so it's quite important to not only present relative risks, but also present the absolute risks. What we see from this systematic review and meta-analysis, it indicates that the prevalence of obesity in adults is around 30 percent, almost 30 percent for those with ADHD, compared to around 16 percent among those without ADHD.

And the corresponding numbers for children is around 10 percent for those with ADHD and 7 percent with those without ADHD. Finally, the final set of results that I want to highlight from this systematic review and meta-analysis was that when they looked specifically at those that were treated for ADHD, the findings actually indicate no increased risk of obesity in those with ADHD. I want to highlight again that there aren't that many studies on this topic and it's a difficult question to address.

So again, more research is needed, as I will point out on the next slide. So, have in mind that the results that I've just talked about concerns cross-sectional data. So there is still a lack of longitudinal studies that explores how ADHD and obesity relate to each other over time.

And this is very important in order to clarify the directionality. Is it ADHD that is a risk factor for obesity, or is it the other way around, or is it potentially a combination of both? Future research is also needed to address the underlying mechanisms. And finally, much more research is needed to understand how ADHD medication treatment influence weight in those with ADHD and obesity.

I will talk a little bit about these two first aspects. I will not talk more about the potential effect of ADHD medication treatment, but will focus primarily on longitudinal relationships as well as some aspects of the mechanisms that could explain the association between ADHD and obesity. Start off with longitudinal relationships.

As I said, we need more research here, but there are a few well-conducted longitudinal studies that have followed individuals with ADHD across time. So here you see one nice example of a controlled prospective follow-up study. So when they compared men with childhood ADHD with men without childhood ADHD, they clearly saw a significant difference when it comes to BMI in adulthood, as well as when it comes to the obesity rates.

So higher obesity rates among those with childhood ADHD compared to those without childhood ADHD. Here's another example of a longitudinal study. This study focused more on the childhood and adolescent period.

So what they demonstrated in this study was that childhood ADHD symptoms significantly predicted adolescent obesity, but not the other way around. So childhood obesity did not predict later ADHD symptoms. Let's turn to potential mechanisms.

And here I will direct you to an interesting paper, quite recent one, that in detail have discussed different potential explanations to why ADHD and obesity overlaps. This review paper brings up potential factors such as genetics, fetal programming, executive dysfunction, psychosocial stress, lifestyle factors, sleep patterns, etc. What I will focus on during the next couple of slides is the potential impact of familial or genetic factors for the association between ADHD and obesity.

So this is something that we have addressed in Sweden using national registers. So what you see here on this slide is a paper that we published a couple of years ago in JCPP. So this is a family study where we use the national registers in Sweden.

So in Sweden we have a conscript register where all males or primarily males are assessed in detail and they are assessed when it comes to BMI. So we have detailed medical assessments of BMI from the general population, primarily men. And then we also have national patient registers in Sweden, which allow us to capture individuals with a diagnosis of ADHD.

On top of that, we have a multi-generation register in Sweden, which allow us to identify all possible types of family relationships. And we use that in research settings to conduct large scale family studies. So what you can see here, I've highlighted one of the main findings from this study.

So siblings of index males with overweight have an increased risk of ADHD. And we saw an increased risk both for overweight as well as for obesity. So this study indicates that it could be familial factors that influence the risk of both ADHD and obesity.

We have conducted another family study in even more detail in Sweden, using the patient registry in Sweden combined with the multi-generation registry. So here we looked at clinically diagnosed ADHD and clinically diagnosed obesity. So what you can see here in the figure is, as expected, individuals with a diagnosis of ADHD have an increased prevalence of obesity.

And this is true both for males and females. What you see at the bottom of this slide is results of quantitative genetic modelling. So we performed statistical analysis to estimate the genetic correlation between ADHD and obesity.

And as you can see here, we observed a statistically significant genetic correlation, indicating that there could be genetic factors shared between ADHD and obesity. And this is interesting for several reasons, but I want to highlight one important reason. I think this finding has important implications for risk factor studies.

What do I mean with that? I will try to explain. A lot of studies have suggested, a lot of researchers, I think you can read it even in textbooks, suggest that maternal pre-pregnancy overweight and obesity is a risk factor for ADHD in the offspring. This is a quite common view and we try to challenge this assumption or perspective in a recent study.

So we conducted a sibling study to explore whether familial factors explain why maternal pre-pregnancy overweight and obesity is associated with ADHD. This is a quite busy table. I will guide you through.

So we start on the left hand side in the column labelled crude. You can see that if we look at pre-pregnancy obesity, we see that maternal pre-pregnancy obesity is associated with an almost twofold increased risk of ADHD in offspring. If we move one step to the right, you see the adjusted column.

We adjust in the analysis for different types of important covariates. We see that the association attenuates a little bit, but it's still highly significant. It's quite substantial.

And this estimate is actually what quite many researchers report when they claim that maternal pre-pregnancy obesity is a risk factor for ADHD. But we continued further and compared full cousins who were differentially exposed for maternal pre-pregnancy obesity. So one of the cousins has a mother with pre-pregnancy obesity or pre-pregnancy overweight, and the other cousin has a normal weight mother.

And what we see there is that the increased risk attenuates even further. And finally, in the column to the right labelled siblings, we compare full siblings who have the same mothers. And given that there are variations in overweight and obesity across time, there are siblings that are differentially exposed for pre-pregnancy overweight and obesity.

And when we compare those siblings, we see no evidence of increased risk for ADHD. So this pattern of result indicate that the observed association between pre-pregnancy overweight and obesity and risk of ADHD in offspring is largely due to unmeasured familial confounding. So it's not due to pre-pregnancy overweight or obesity per se, but underlying background factors.

Okay, so I have talked a little bit about the prevalence of obesity and overweight in relation to ADHD. We presented or we saw some studies exploring the longitudinal relationship between ADHD and obesity. And those studies, those initial studies indicate that it's probably ADHD who precedes obesity rather than the other way around.

We talked a little bit about the mechanisms. I presented results around familial slash genetic factors. So now I want to move forward with a couple of slides dealing with consequences of obesity in ADHD.

So this is an important focus of time span. Of course, we have just started time span, so we don't yet have a huge amount of results, but we do actually have one recent study that just became accepted for publication. So I will present a little bit about that study and leave it with that.

So I'll start off by presenting or directing you to another useful paper. It's a review paper by Sam Cortese and colleagues. This is really the first example that I have seen in the literature where they discuss the potential impact of ADHD on the treatment and the management of obesity.

They clearly highlight that there are still a few studies, but those few studies indicated something interesting. First of all, they indicate that individuals with ADHD might have a poorer prognosis when it comes to obesity and that there are problems related to treatment. Very preliminary studies also indicate that appropriate ADHD medication treatment might help in the management and treatment of obesity.

So this was an early paper. I haven't seen much research on this. There are still lots of knowledge gaps around this, and I hope that our project time span will address some of these knowledge gaps.

And we have actually started, as I just said. So what you see here is a paper that we conducted in Sweden. It's accepted for publication.

Just this other week. And this study explores the association between ADHD and outcomes after bariatric surgery. One very unique thing about this study is that we use the Scandinavian Obesity Surgery Registry.

This is a very unique register that allows us to identify many people who have undergone bariatric surgery. So in this study, we explored short and long-term outcomes after metabolic surgery in those with and without ADHD. We identified almost 60,000 individuals, adults, who underwent bariatric surgery.

And we compared those with and without ADHD across the follow-up period. The main findings in this study indicate no differences in weight loss when we compared those with and without ADHD. We saw a slight increased risk of post-operative complications, but not for the severe complications.

When we look more into long-term effects, we saw differences in self-harm, substance abuse, and quality of life when we compared individuals with and without ADHD. So if I should wrap up and summarize, individuals with ADHD are at increased risk for overweight and obesity. Longitudinal studies indicate that ADHD probably precedes obesity.

Familial and genetic factors are one important factor explaining this association, which also indicate that maternal pre-pregnancy BMI is probably not a causal risk factor for ADHD in offspring. And as you just heard, when I presented and talked about consequences of obesity and ADHD, we saw that individuals with ADHD experienced similar weight loss and remission of obesity-related diseases. And we did not see evidence for serious complications, but we did see an increased risk of poor quality of life, as well as increased risk of substance abuse and self-harm.

That was my presentation. Thanks a lot for listening. Happy to take questions together with Tony.

Thank you both very much. We have an earlier question from Luca, if we can start with that one, which was, he said, thank you for a nice talk. You mentioned the association between ADHD and eating disorders.

Do you have data more specifically for binge eating disorder? Yes, that is a good point, because also it is nice to remember that one of the drug treatments that we are using for ADHD during childhood and adulthood, Listexamphetamine also, it has indication of binge eating disorders. Also, it's very common, around 20% of these patients also have ADHD, as very similar with bullying and nervous system. And in this patient, the profile is more severity of this binge eating disorder and also more complication with other comorbidities as a substance disorder, or for example, you have suicidal ideation or to have suicidal behavior also.

Okay, lovely. I think Luca's still with us because he's added another question. Which was, do the increased risk of substance abuse after bariatric surgery in patients with ADHD include alcohol abuse? Well, in fact, the link between ADHD and substance use disorder, in fact, is a very genetic risk factor, because we, for example, we studied in the Brain Storm Consortium with several mental disorders and also neurological disorders, and was published, I think, four years ago in Science, that there are high overlap between genetic risk factors of these disorders.

And for example, for cannabis, it's absolutely clear with random Mendelian analysis, when we studied the causal factor, ADHD, the genetic profile of ADHD is a clear risk factor for having substance use disorder. In this case, with alcohol, we know that people with ADHD have an increased risk for alcohol, and also in this patient, more than the genetic risk factor or the polygenic risk score in this case, is that the high levels of impulsivity and the high levels of emotional dysregulation is a risk factor also for all of these substance use disorders. I think after the surgery, it's not an increased risk specifically.

There are increased risks before the surgery also. Correct. And if I just very quickly, I mean, I think alcohol use disorder, alcohol increased risk of alcohol use disorder is a concern and something that a lot of people discuss in relation to bariatric surgery.

We looked broadly into substance use disorder where alcohol abuse is one diagnosis among several. So we did not look specifically at alcohol use. Hi, Luca, I can see you on the call.

Is there anything else you'd like to ask? No, thank you for the nice talks again. I am concerned with the alcohol abuse after bariatric surgery exactly for the reason that Enric mentioned. So probably alcohol abuse is the most common substance abuse after bariatric surgery, and particularly after gastric bypass.

But I agree that this should be a part of a common pathway, of course. I have an additional question for both or for Tony, maybe. You mentioned impulsivity.

And I think that this could be a very very shared psychological trait in between people with ADHD and people with obesity, in particular people with obesity and eating behavior disorder, because several studies regularly demonstrate this trait as a marker of people with binge eating, lack of control, emotional eating. This could be very interesting in my opinion. Yeah, I fully agree with you, Luca, because that is a very, I think, transdiagnostic profile of symptoms.

And also the impulsivity is absolutely linked with this idea. In fact, why people with ADHD have this, for example, when we studied what is the profile of diet, if a healthy diet or not, it's terrible in this term. This is a very unhealthy diet and absolutely disorganized, it is like a chaos.

Moments of eating around the day and other moments to have these binge eating disorders, it's quite common in general for ADHD patients. And this impulsivity and the inattentive symptoms, these problems for organizing, for planning, for schedule activities, the most severe patients are very critical. And I fully agree with this impulsivity, and also impulsivity related with this emotional dysregulation, yes? In this sense, in terms of prevention, with the drugs that we use it for ADHD, stimulants or non-stimulants, and also the psychological treatment, one of the focus is to reduce this impulsivity, to reduce this emotional dysregulation.

And at the end, they have more time to think before to act, yes? And that is one of the key points. I agree completely. And I think we can, I mean, you're sort of addressing a question from Lisa, who writes in the chat, thank you for a great webinar.

Do you know whether there are, whether any specific dietary patterns may be linked with symptoms of ADHD, either in childhood or in adulthood? And you're sort of, you highlight that, Tone. I mean, we know from research that when we study dietary patterns in those with ADHD, we tend to see unhealthy dietary patterns. We did, just a couple of years ago, a correlational study where we just calculated the association between ADHD symptoms and measures using a food frequency questionnaire.

And we saw a significant association between ADHD symptoms and high-fat, high-sugar food types. And I think, I think that also links up to that question and what you just discussed. And also, it's interesting regarding the diet that now in another European grant, and we collaborate together, it could be nice, we try to study all of these patterns and also to study with several different clinical trials, if for example, that diet restrictions of some specific foods will be helpful for children with ADHD.

And also to introduce the use of prebiotics, yes, because we have a previous data that there is a signature profile of the microbiome that is with differences regarding the general population in adults with ADHD and also in children with ADHD. But clearly, we need more research in this aspect. We will have the data for these clinical trials will be available, I hope, in a few weeks and will be open.

Cool. Can I continue and take questions? Because I have one here around socioeconomic status. Was that adjusted for in the analysis that I presented? And overall, yes, I mean, in socioeconomic status is an obvious covariate to adjust for.

I would assume, I can't talk for all studies, but that most studies has adjusted for socioeconomic status. Maybe, Tony, emotional liability as another explanation on top of impulsivity. I think that's an interesting one where you can perhaps say something.

No, no, no, it's a full area, as I said before, because these transdiagnostic profile of symptoms are very common in other disorders also, but could be a link and a possible explanation, yes, between ADHD and obesity. In fact, this genetic correlation that we can find also maybe will be tried to alter or to have different genetic profiles that can modify these traits or these symptoms, yes. I like to see ADHD as a disorder of opportunities because when someone has a depression or a bipolar disorder, in the majority of the cases, the first episode will be during the adulthood, for example.

But in this case, we have a disorder that started during the childhood, and we can introduce preventive measures to improve this diet perspective, for example, or all of this emotional education in order to keep with the life challenges, yes. There is one question around OCD, whether we know how to demoderate the association. I don't have a straight answer to that.

It would be interesting if you're on the call, I mean, if you want, you could clarify a little bit what your sort of, what your questions were. Eugenia Romano? Yes, hi, I'm here. Yeah, I was curious because sometimes reading about ADHD, thinking about OCD, there are some things I think kind of overlap, and sometimes I think, you know, they could even come together as morbidity.

And I was curious about whether some traits that may be specific of OCD might moderate the association between ADHD and obesity, because it would be something interesting. It's a curiosity I have, something I was thinking about while listening to your presentations. Well, OCD and ADHD or obsessive symptoms are quite common, but also these OCD symptoms and ADHD, very, very common.

In general, the patients with ADHD has these symptoms of some impulsivity together with OCD. It's not the most common morbidity associated with ADHD, but in some cases, it's like a secondary effect that we can see with stimulant drugs, yes? Some of the stimulants drugs are dopaminergic drugs, and for some patients, it's a side effect. One of the best recommendations that I can give you today after this talk is to use the SSRS rating scale, because it's very simple.

It's validated in all of the languages that we have here today, investigators. You can screen very simple patients with ADHD, and you can have another opportunity to treat better this eating disorder, this binge eating disorder, and also the obesity. You can detect the patients with the... If the patient has a negative result, negative score, it's not necessary to continue more assessment, because in this case, you have a good negative predictive value.

The positive value may have in some cases to continue asking questions about during childhood symptoms, if these symptoms were present during the childhood. But I think it's a very useful instrument in your day-to-day, and also performing, I think, studies, research, would be useful for you to have these clusters of patients with a clear ADHD that can explain better some of these impulsivity symptoms, or better result, or negative outcome regarding obesity. Yeah.

I don't think we... Have we missed any questions, or are there any further questions? I've just checked the chat. I think we've covered most of them, but Lucas just raised his hand, so if you're happy to take another. May I ask a question, probably not directly related to the contents of your presentation? You mentioned the role of lisdexamphetamine in the treatment of ADHD, and these drugs in the United States has been also approved for the treatment of binge eating disorder, but probably this drug will never reach Europe for the concern that we have about the possible abuse of these drugs.

So, maybe you have more experience than me with this kind of drugs. What do you believe in the long term? Because I know that the approval in the United States for binge eating disorder is based on a very small, short-term trial, so I am not so sure about the risk-benefit of these drugs in the long term. What about the role of these drugs in your field, in your area of interest? I think you can start, Tony.

Sorry, yes, I was muted. After months and months and months, I'll be here. Yes, Luca, thank you so much for this good question.

I have experience using the stimulant drugs for more than 20 years, but specifically for ADHD. Yes, under my experience, one of the challenges that we have is not the abuse of these drugs. The challenge that we have is not adherence, because they are very inattentive, chaotic day by day, and we need to introduce applications or reminders to not forget to use or take the medication.

In terms of cardiovascular profile, yes, we published a study with a long period of time taking an echocardiogram and also blood pressure, yes, and heart rate, and there are only a little increase of arterial tension, but this is without a clinical impact or a clinical significant, because it's one true point that you can have in the majority of cases, yes. Is it Tony who has a connection or is it me? No, I think it is Tony. It's Tony.

Yes, so I think, I mean, I'm not a clinician, so I can't really respond in detail to what I think will happen when it comes to pharmacological treatment for ADHD and whether that will be, those drugs will also be used in the context of binge eating. I don't have a clear perspective on that, but I'm happy to take other questions if you want. We don't have any other raised hands at the moment, but if anybody has anything they'd like to ask Henrik, please feel free.

We'll pop it in the chat if that's easier. I think we've lost Tony completely now. No.

So maybe I can just end off with a 30-second pitch for sort of, I mean, so what we have talked about ADHD today, that is our main focus in time span. I hope you sort of find it interesting to think a bit more about ADHD in the context of overweight and obesity. I think it's super interesting both in terms of, I mean, if we want to reduce the rates of obesity, I think it's important to think about ADHD as one potential risk factor.

So that's one thing. And the other thing is, of course, that we have touched upon a little bit. I think it's interesting to think about ADHD when it comes to the treatment outcomes, when we treat and care and manage and try to manage obesity.

I think ADHD is an important factor to consider. But on top of that, I just want to pitch that overall, I think mental health, mental health, psychiatric conditions is a key factor to consider and study in detail in the context of overweight and obesity. Yeah.

Yeah, very much agreed on that point. Thank you so much to both of you, to Henrik and to Tony, who I think has come back now. Yes, sorry.

I had some technical glitches. Sorry, sorry, Luca. Yes, very, very quick.

As I said, there are a profile of patients with high risk. This is patients with ADHD plus, antisocial personality disorders, because they can deal with, we say, in the black market with people without ADHD. Yes, that is important.

Sorry for that. That's OK. We've done well, really.

I'm going to pause the recording now. Unless there's any other final comments from yourself, Tony, Henrik, just another lovely nice summary for us. I mean, thanks a lot for inviting us.

It has been, I mean, a real pleasure presenting and discuss with you. I hope to see you in the future. Sure.

Thank you so much, guys.