Dr. Sandra Kuey (19:00)
Agents, not risk accelerate your AI transformation@rubrik.com that's R U B R-I K.com okay, what are we looking at? ADC causes sleep problems, that's for sure. Because if you're restless and you cannot. Oh, it's not. Oh yeah. ADC may cause fear problems because of restlessness and erasing thoughts and not being able to put off the motor at night. But we also know that sleep problems cause ADHD symptoms such as less focus, memory problems, mood issues, Irritability, but maybe it's also true that both interact and that they increase each other. And maybe there's even a fourth idea that ADHD and sleep problems have a shared underlying etiology. And the red ones are the ones that I go for, as far as I know now. So if there's a shared underlying etiology, it might have to do with the brain and the clock that is regulated in adhd. The clock is late. I'll tell you more about it, which may induce both ADHD problems and sleep problems. To be continued with more research because we are still beginning to see the picture. Okay, this late sleep problem, what is it all about? It's called delayed sleep phase syndrome and it's characterized by a late chronotype. You are genetically late person. You tend to go to bed late after midnight, because if you go to bed at an earlier time, it's not easy to fall asleep. You may lay awake for hours and you get annoyed by that. So you jump out of bed, start doing something else, use a lot of light. You use the computer, of course, at night, and then you may even delay your sleep phase further because if you use light at night, you stop the production of melatonin, your own sleep hormone that only starts in darkness. So good to know. But it's not a cause of the late sleep phase disorder. This late sleep phase disorder is a genetic based sleep disorder that's highly prevalent in ADHD people, about 80%. The results are daytime sleepiness, difficulty falling asleep on time. You may compensate for going to bed very early, late, very late and back. So you get an irregular sleep pattern, trying to compensate all the time back and forth for sleep loss, but it leads to impairment during daytime due to inattentiveness and of social difficulty. Okay, yes, there are clock genes. Clock genes are genes that dictate what kind of an early bird or late bird you are and you inherited from one of your parents. So usually you can find back in your family the roots of late and early chronotypes easily. Okay. If you have this lateness, this genetic makeup, this late chronotype, they set the time of your clock, but the time of light onset, opening your eyes in the morning, letting the light come in, is also important to set the rhythm. So you can influence this late clock time by light exposure. And when light is on, melatonin goes down and dopamine is going on. Dopamine is important for ADHD people as it is the neurotransmitter involved with attention, impulse control and mood improvement. So basically, I tend to think about dopamine now not only as a neurotransmitter, but also as a daytime hormone because it starts with light onset and melatonin is nighttime hormone, and it's. It stops with onset of light, and it starts when it's getting, getting dark. And then dopamine stops again. So this is really a 24 hour cycle in which both are not at the same time active. And then we have the eye through which the light enters the brain. And in the eye there are receptors in the retina for melatonin and dopamine. Isn't that interesting? So the receptors in the eye receive the light per input, and they tell the clock that's behind the eye here in the midbrain, what time it is. That's so interesting. So the intensity of light is measured through the eye, through the melanopsin receptors, to be precise. And they tell the clock what time it is, is it time to make a start with melatonin production or not? And so on. And every other rhythm is being regulated through the clock and the input of light and darkness through the eyes. Here you see a cross section of the eye. Here is the retina. The retina, sorry. And the retina is here enlarged. Here you see the melanopsins receptors here, the rods and cones that see dark and white and colors. You may have learned that at school. But these melanopsin receptors are pretty new. They have only been detected 15 years ago. And they are sensitive to the light intensity only. So if the sun is shining and light enters the eye, it's told what time it is two clock over here. And light is associated with more energy, a better mood and a better sleep at night. Because in order to sleep at night, we need a lot of light during daytime and we need complete darkness at nighttime in order to facilitate these processes here. Okay? Having said that, people with ADHD do not always behave the way that's most beneficial for them because they tend to wear sunglasses. In 70% of my population, I asked this question, almost 500 people, because I found out in my clinic that people came in with sunglasses often, also when there was no sunlight, also when it was winter and rather gloomy weather. And I asked them, why do you wear sunglasses in this type of weather? There is no light to protect your eyes from. And they told me, well, yes, I'm oversensitive to light. And I got the same answer all the time. And I got intrigued and asked them, a whole group of people, whether or not they had ADHD and whether or not they wore sunglasses during daytime in every season and how many hours in every season. And it proved that the people with ADHD wore sunglasses a lot of time, many more hours than controls and much more frequently than controls in all seasons. So no matter whether it was summer or winter, and if you do that, if you wear sunglasses during daytime, your brain will perceive your environment as dark and will think that it's nighttime, so you don't synchronize your biological clock, your rhythm with daytime. Same is true for people who work all the time indoors without much light exposure. So it's very good and healthy to walk a dog in the morning, to have a walk during lunchtime, in order to have any clue about time of the day and have some light input for your system. Because we need contrast between night and day. We need bright light during daytime, darkest night as possible, because it gives us stronger signal to the clock. It helps us to synchronize with the day of time and the day of the night. So no sunglass during daytime. Sorry. And no lights at night, of course. Because if we do the opposite and we use light at night in bed, with iPads, televisions, iPhones, close to the eyes, it emits a lot of blue light that prevents melatonin to be produced, and so you won't sleep for a long time. Okay, this one is about the prevalence of ADHD in the United States and the light intensity in the United States. This is interesting. This researcher from my country tried to connect the dots between both, seeing that the highest prevalence of adhd, the darkest blue here, is in the east of United States, and the lowest is here around Mexico. And. And when you look at this other map of the light intensity in the United States, Mexico is the brightest illuminated part of the United States, and here in the east coast is least light exposure. And he calculated solar intensity and the prevalence of ADHD and found that 34 to 57% of the variance in ADC prevalence could be explained by solar intensity. So what does that mean? As far as I understand, means that if you have a brighter day and darker night, because Mexico uses much less artificial lighting, you have more contrast between day and night. You will sleep better as a population, and ADHD people will have less problems because they may not even touch the symptom threshold for diagnosis, leading to a lower prevalence rate. So important is sleep for people with adhd. Just to give you an idea, this is a study from my team in 2010. We measured the onset of melatonin in saliva in dim light conditions. That means with no Light exposure, only a little bit of light because people had to swallow, no, not to swallow, to use saliva on a cotton swab, swab. And it has to be stored in a fridge beside their bed every hour from 9 to 1am, 9pm to 1am and we measure this in people with ADHD and sleep on sleep onset insomnia and ADHD without sleep onset insomnia. And this was the smallest group because most people had these problems with sleep onset. And we found a huge difference in the onset of melatonin between both groups, but also between the groups. And healthy controls, healthy controls in my country have their melatonin onset at 9:30 and in ADHD it was at 11:15 or at 10 in those without sleep onset instruments was highly significant. It means that there was a one hour and a half delay in onset of melatonin. And this might very well explain why people with ADHD in the majority of cases have such a late sleep onset. Because if you have this DIL mode, this melatonin onset at, let's say 11, it generally still takes two hours to fall asleep, but in ADHD it usually takes three hours. So also the sensitivity for melatonin seems a bit lower. And then if you calculate this, you easily come at a bedtime or sleep onset time of 2 or 3am as a rule. This picture shows the same study showing the 24 hour movement patterns in people with ADHD plus and minus sleep onset insomnia. So this is the people with sleep onset insomnia and this is without sleep onset insomnia. The light gray, dark gray is shifted to the right as a whole. And this is the nighttime movement so reduced and this is daytime movement so increased. And this difference is exactly the same amount of time as the melatonin onset lateness. So one hour and a half. So the movement pattern the next day was also one hour and a half delayed. If ADHD is basically jet lagged, because I think that's what we're looking at, or out of sync, what else might be out of sync? Because it's sleep time, it's melatonin onset, but it's also a movement pattern. But it may also be related to this late appetite and the late breakfast or skipping breakfast that many people with ADHD show we measured in another study. Their temperature profiles, both from the outside on skin as well as after swallowing, ingesting a capsule that measured the internal core body temperature, it showed basically same curves, a low temperature at night and higher during daytime, which is normal, but also a shift to the right lateness of this temperature profile compared to controls. So maybe we should consider adhd, not only a problem of daytime, but also a problem of nighttime, including late sleep and nocturnal presentation of rhythm disturbances. ADHD happens to be related to winter depression, seasonal affective disorder. That means that you may have two or two weeks or more of low mood starting autumn or winter and resolving in spring or summer. When the light comes in. It's associated with increased appetite for especially carbohydrates and chocolate, of course, weight gain and increased need for sleep in winter and low energy. This winter depression comes often with a late sleep pattern or late chronotype and adhd. And it happens more often in women than men, female male ratios 4 to 1. And the prevalence of winter depression depends on latitude, say light input. So we have, for instance, 3% winter depression in the Netherlands, but 10% in Norway, because it's much more up north with shorter duration of daytime light in winter. So you can extrapolate this for certain states in the United States where you have more and less light in winter. Dutch ADHD patients have been studied by us and they report in 27% winter depression. So let's say around 30. So the prevalence is nine times increased compared to the normal for circulation. And it has something to do with the late sleep pattern and the latitude. Of course, the good news is you can treat winter depression very effectively by light therapy. In one to two weeks, you have a better mood, better sleep, more energy and a decreased appetite. So you're able to control your appetite and decrease weight, probably. Although repeated episodes of light therapy may be necessary during winter, here are some references to study further. This slide refers to the Nobel Prize for medicine in 2017. This is a Dutch newspaper telling that the Nobel Prize was for geneticists that found out about the genes that code for the biological clock. Well, you might think this physiology is not important. Why should we know about it? But it is important for medicine as a whole. The rhythm of the system, of all organs, of all processes in the body, is related to health and disease. So that's why it's important. And that's why it's important in ADHD as well. Having said that, we have a delayed circadian rhythm in at least 75% of both children and adults. It has been measured in children as well. So it starts early, it continues. It's basically a biological pattern during your lifetime and it leads to short sleep duration because you can only sleep late and you have to get up in the morning, unless you have another job or you are an artist working at Night, which also has some disadvantages. Short sleep in the end induces increased appetite and increased appetite in juices. Obesity, especially when chronic. And when you say obesity, you get these others for free afterwards. So diabetes, cardiovascular disease and cancer. So it's something you should try to prevent to become obese. And you can only do that by treating your sleep problems from the beginning. And there is a lot of factors involved that lead to these outcomes. But we should think about what we can do about it. Because if we sleep not enough or bad, we will have, we suffer from low mood, we will have an inclination for more eating, growing fat, having ADHD and so on. It's endless circle. Yeah. How do you get ill if you are obese and have adhd? Well, you have so many factors that drive obesity, in fact. So you have this winter depression, seasonal affective disorder, 30% in ADHD. And it comes with carbohydrate cravings in winter. And it helps improve your mood a little bit for a short time. It's not a good therapy, but it does help and people do it because of this winter depression. You have late sleep in 80% of people with ADHD leading to short sleep duration, leading to altered leptin ghrelin ratios. These are the appetite hormones in your body and they respond to short sleep leading to carbohydrate cravings. You skip breakfast, which in itself leads to binge eating later in the day when there's no healthy food available and you may eat unhealthy fattening food, and then you grow fat and develop obesity. Obesity is basically a low grade inflammation for your whole system, for all organs. It's very, very unhealthy to have to be obese in the long term. And this inflammation induces this kind of diseases and many others. Now about the good news. What can we do about it? The treatment of the late sleep phase syndrome and winter depression. Also because they're treated by the same therapy, chronotherapy. It means resetting the clock, advancing the clock, and it starts with sleep hygiene. But sleep hygiene alone is not enough because people with ADHD have to battle with a real biological delayed rhythm that they cannot change on their own. They can work very hard to sleep earlier, but it's very difficult to maintain such an earlier rhythm if you have this genetic makeup. So you need melatonin to reset and advance the clock. And you need light therapy in the winter to get up early and easy and without having any mood problems in winter. So here comes my tricks. Let your day be bright and your Night as dark as possible. This is basically the idea. And how can you help yourself to sleep through? Don't drink too much after 8pm in order to prevent toilet visits. And if you have to visit the toilet, use no light. Because of obvious reasons, when light enters the eyes, your melatonin production will be stopped immediately and it will take a longer time to be able to fall asleep. So what I do if I do need to get out of bed at night, I don't use the light. I keep my eyes closed. And because I'm very well aware where everything is in my bedroom and in the bathroom, I do this without any accidents. But you should take care that there's an open space where you can walk without having any accidents. It's important to make your bedroom very dark. Block all light sources. Blinded curtains, no looks of legs for instance. Wear a very good closing eye mask. No lights of charges time as mobile phones that can wake you up at night. And please no screens after 9:30 because 9:30 is the time that melatonin rises in normal population. But in ADT we now know it's later. But just try to prevent to delay your rhythm even further by using screens after this time. If you do need to use screens for work or what else, please use orange goggles here there. Because orange goggles prevent the light from screens to enter your brain. The brain thinks it's dark when you wear a glass with orange goggles, same as with dark goggles. But the trick is that you need to do it from 7pm because then you may have an earlier onset of your own melatonin because your brain thinks it's already darkening at 7pm so that's interesting. Then you don't even need to use melatonin if you do this every day from 7pm until bedtime. Where am I here? The temperature control. Temperature is related to melatonin. The melatonin onset and downset. So if you take a hot shower at night and not in the morning, it's profitable because it helps you cooling down just before bedtime and cooling down just before bedtime with warm feet however, helps to fall asleep. Try to wake up every day at the same time in the morning, including on the weekends. Whoa, that's bad. I hear you thinking. Because you want to sleep in in the weekends when you're exhausted to sleep last during the week. But if you do this, you won't need any sleeping in in the weekends anymore because you're on a stable rhythm. That's what you basically need to feel more stable and Happy. The aim is a sleep duration of 7, 8 hours and preferably between 11pm and 7am and you will say to me, if you never used chronotherapy, I cannot do that. I'm sure I cannot do that. I'm not listening anymore. But I invite you to listen, because most people say that to me. And after two weeks they can sleep between 11 and 7, wake up before the alarm goes off, really. And have much longer sleep duration and better sleep with chronotherapy. Also when you're night owl. But you need to take into account all these kinds of advices. For instance, don't go napping during daytime. People who are exhausted do nap during daytime. And if you do need to nap no longer than 30 minutes, so use an alarm, because if you go into deep sleep, you will really have difficulty to fall asleep at night, because all sleep is accumulated in a 24 hour sum. And if you use it already during daytime, you won't get it back at night. Go outside in the morning to be exposed to light. Walk a dog. Advance tourism by light in winter. If it's necessary. I'll tell you more about it. Limit use of sunglasses during daytime for obvious reasons I discussed, and this is the story about the obvious sensitivity to light. And that's the reason why people use these sunglasses during daytime. But they disturb synchronization by light during the day because the light cannot tell the brain what time it is when you use certain glasses for many hours a day. Then melatonin, the sleep hormone, it's very effective, in fact, for people with a delayed sleep phase disorder, it's in fact the indication for melatonin use, not the other sleep problems. So don't try it for restless legs or sleep apnea. Insomnia might be helpful because it often overlaps with late sleep phase, but the dose is pretty low. And this is maybe new for people in the United States who are able to buy dosages of 5 to 10 milligrams at the drugstore. But the advice is to use really low dosages, because if you use higher dosages, the result is not better. In fact, the result is pretty good with these low dosages. And if you use the high dosages, you will have hangover the next day because melatonin is not cleared from the system so fast. So the higher the dosage, the more hangover you will have the next day and it will lead to more sleepiness. So you will sleep better at night, but you will also stay sleepy during daytime, which is not what we're Aiming for. We want you to to have a bright mind and able to focus. This low dose has been studied by us and it's very effective. So I'm really confident to tell you that it's really true that you can do with this low dose at 10pm for instance, using a timer. If you are a very, very late person that only goes to sleep at 5am in the morning, it will take a week to get to an earlier rhythm that we want if you start at 10pm so you could also start later and then advancing back until you are arrived at 10pm and can sleep at 11. Melatonin works only 3, 4 hours. So it's basically something that helps to induce sleep, but it's not helping for sleeping through. There is also long acting melatonin, for instance circadian 2mg and it's also of label available in the United States. Also 1 milligram. It may help in case you wake up at 3am after using short acting melatonin. And you need a prescription for this long acting melatonin in my country, but I'm I think not in the United States. Okay, here's the light box that can be used for light therapy to wake you up in the morning at a fixed time and also to treat winter depression. Because in winter when it's dark in the morning, your sleep may be further delayed because you're not. The sun is not waking you up in early morning, but only at 10 in the morning or so. So it induces disturb mode this late light onset. So we can improve your situation by adding light early in the morning and you use a timer for that. Otherwise you sleep in all the time, you forget to do it. So use a timer for that. It's called time warning light and it solves the problems of the biological clock, both late sleep and winter depression. How can you do that on your own? Because it's a do it yourself therapy, basically. So that's good news. Well, winter depression may start in September and it lasts till April. It's in fact dark season. And in April there's enough light and early light to do the job by nature. And you start after having two weeks of a low mood, low energy and increased appetite. You use light therapy a minimum of five days, up to 21 days for 30 minutes every morning. And the light box should have a intensity of 10,000 looks at 20 centimeters from your eyes. This is really, really close. It's only this close. So you almost cannot have a book between your eyes and the light box and your and your body. And it's essential this close distance. Otherwise you need to sit there much, much longer for an hour or so. And that's something you don't want to in the morning. So you have to look at the intensity of the light box, the distance from your eyes, the duration and the consecutive days that you need. You do light therapy every morning at the same time before 10am because and preferably a bit earlier, between 7 and 8am in order to pretend it's summer. Basically 10am it's still midnight, late winter time. And here it's starting to become summer. If you can. If you are able to get up early in the morning refreshed and well, you can also buy light glasses. Here they are. It's a new invention from my country, among others. So you don't need to sit still behind the light box, but you can wear 30 minutes while dressing, having breakfast, which is much more convenient. But when not to use light therapy. If you have bipolar disorder of have been may have had mania or hypomania. It may be induced in people with this condition because it's a real antidepressant. So it does the same as an antidepressant in bipolar people who do not use lithium or adepakotes. If you're suicidal, you first need to see a doctor because you need treatment for that first. Here are other contraindications. Epilepsy, narcolepsy, skin cancer. This medication. Fever, first trimester pregnancy, retina problems. These people who have these problems or conditions should first talk to the doctor. So it's not everything. Do it yourself. You have. There are some rules and you can evaluate light therapy after 7 to 10 days and again anytime the next week. If you say, well, I feel better, but it's not enough yet, then you can continue for two to three, three weeks. The first improvement may start already after three days. And it may start with a labor mood. And it's an indication that mood is changing and improving. Basically because if you're really depressed, you don't feel much, then you get labor mood and then you get in better mood. You can use light therapy one to four times several weeks during the season if it's effective. And your atypical symptoms of depression, such as increased appetite, weight and increased sleep need they predict response to light therapy. So they also improve. You must start soon after the onset of symptoms. But you cannot prevent winter depression by starting before the emergence of symptoms. Here are some available light boxes. Blue light white lights and the glasses propee glasses. We use these glasses A lot. And this is a discount code that you can use when you enter this site. And here, this, this propyl glass also has these orange goggles for the nighttime prevention of light entering the brain when you need to use screens. There's more information at the Society of Light Therapy and Biological Research here and the National Sleep Foundation. A lot we learned about rhythms and sleep and adhd. The wake up light is very popular around Christmas as a present for people who have difficulty waking up in winter. But it's not a real light therapy light box. For that reason you need to turn to boxes that have 10,000 lux intensity. Yes. Having said that, that ADC and late sleep are so closely connected and so frequently coming together in about 80%. There are people that said already in 2017, if we correct the lateness of the sleep disorder in people with ADHD with bright light in the morning, can we also predict improvement of adhd? And the answer in this small pilot was yes, we can. So ADHD gets better by light therapy alone. Interesting. Not. And we did this one studying the effect of 0.5 milligrams of melatonin low dose in people with ADHD and delayed sleep phase. And we also found 14% improvement of ADHD. So that's not nothing. It's not much, but it's also not nothing. And it means that if you are not ready or you don't want to use medications, you can at least start to improve your sleep using melatonin at night and light therapy in the morning. This is the study. Basically we wanted to know whether chronotherapy could improve and advance the rhythm, improve sleep, improve ADHD and maybe had also impact on certain health biomarkers. And this study was done By Emma Van Andel, 51 Adults with ADHD in late sleep. Sorry, I got too fast and oh, I can't move. Oh yeah, here it is. Yes, sorry. Everyone got sleep education and three weeks of treatment placebo melatonin or melatonin plus light therapy in the morning. And the timing of the melatonin intake was based on their individual rhythm at baseline. We measured at baseline directly after treatment and two weeks after end of treatment. And we measured melatonin onset actigraphy to measure all the movements with this risk worn device and the ADHD rating scale. And here are the results. The dim light melatonin onset advanced 1 hour and a half using only melatonin and 2 hours using melatonin and bright light therapies. So that's proven effect, that's proven effective for advancing the rhythm the rhythm is so got green here because chronotherapy does advance the rhythm in adhd. And the next one is sleep. What are the results here? Sleep time was at baseline between 1am and 9:30, so they slept it seemed eight hours, but the net of sleep duration was only six and a half. We could measure this objectively with this actigraph. The sleep Onset latency was 20 minutes, but people were 111 minutes awake after sleep onset. So this is how we got only six and a half hours of real sleep. At the end of the study. The sleep was not advanced or any longer, which was a bit disappointing because we hoped that people were able to sleep earlier with this advancement of the melatonin onset which, which was proven but they didn't change their habits. So sleep did not improve in this study. And this we learned a lot from it because we concluded that we should instruct them much more intensive during the such a study and also during treatment with cognitive behavioral interventions. Then adhd. ADHD according to the ADHD rating scale improved also significantly after advancing the sleep phase, but without improvement of sleep. ADHD nevertheless improved 14%. So that's interesting. Although we had hoped for for a better sleep as well. Yeah, and it's only with 0.5 milligrams of melatonin. And we concluded we need more intensive sleep coaching as well in order to change habits that people are used to have regarding sleep time and onset of sleep. The timing of light therapy may need also an individual advancement. Not starting straight away from 7 to 8am but maybe starting at 10 and then advancing back to 7 to 8. Yes, ADHD improved although sleep didn't. The rhythm advanced by chronotherapy. And here is the conclusion. Melatonin should be an important part of effective ADHD treatment, but sleep coaching is also needed. The next study we're currently analyzing is light therapy alone for ADHD. In this study we had 28 adults with late sleep and or winter depression. They got two to three weeks of light therapy 30 minutes in the morning based on individual timing without any medication. And we measured effects on ADHD using the rating scale but also the cubit test that is an objective test for ADHD severity. And we measured depression with a questionnaire as well. And first analysis showed that both objectively and subjectively measured ADHD symptoms as well as depression decreased after 2, 3 weeks of light therapy. So that's good news as well. Light therapy alone may decrease both ADHD and mood in adults with ADHD and late sleep and or winter depression. And these findings are clinically relevant. To be continued. This is already the end of my story. I have some resources for you. The ADC power bank with a short video 34 on all kinds of interesting topics. The idea is that both professionals and patients can use these videos and may speak the same language after having seen those videos, which is I think what we should strive for. The Divacenter EU is this website where the diagnostic interview for ADHD Diva 5 is presented in 37 languages now. And we also have a young Diva 5 and a Diva 5 for people with intellectual disability. Then the latest innovation is the Head Heart Hormones Network you may have heard of. It's for women with ADHD who suffer from hormonal mood changes across the lifespan. That means more premenstrual depression, postnatal depression and perimenopausal depression in adhd. And we want to know what the impact is on health and cardiovascular health, especially during perimenopause. It is a Dutch website, but there's also in part English translation and we are working on that to improve that. Thank you very much for your attention and here's my book and more podcasts at YouTube and so on and Bao bank. Thank you very, very much.
