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Webinar: Severe Irritability and DMDD in Youth -- Dr. Kenneth Towbin

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Severe Irritability and Disruptive Mood Dysregulation in Children and Youth Webinar

Dr. Kenneth Towbin: Well, good afternoon everyone. Thank you for tuning into this webinar on what in our locale is a lovely winter afternoon. In anticipation of maybe tomorrow's big snow fall. I'm Kenneth Towbin, I'm a child and Adolescent Psychiatrist and I work in the Intramural Program at the National Institute of Mental Health. Where I'm involved with a group of investigators who are actively looking at and trying to understand a common problem of severe irritability in children and youth. The talk today, let's just see if I can advance my slide here, thank you, is outlined here and what I want to start to talk about is just a little bit about what we mean when we talk about clinical research and then we'll move through and talk about each of these other topics, but really how we became interested in irritability, how it relates to something called pediatric bipolar disorder and some of the controversy related to that diagnosis. Some features about this feature of severe mood dysregulation that the group here has written about, and this new D.S.M. diagnosis of Disruptive mood dysregulation disorder. And by talking about some diagnostic and treatment implications that follow from this work and offers some assessment tips and guidelines. So, let's start by talking about what clinical research is. So the important feature is that clinical research is a study of people. And it really is designed to help investigators learn about ways to treat those people. To prevent their illness from either appearing or worsening. To improve our ability to make diagnosis and to really understand mechanisms of the disease. I'm so sorry something appeared to have come up that I need to go back here. So clinical research really begins with an idea or question about a disorder and for us you'll see how the question became formulated. When one starts with that question you then generate something called a protocol in detail. And the protocol really says why that idea or question is important and what's known about it already. It also sets out in clear ways who can be included in a study and the scientific rationale for including those people. And who cannot or should be excluded from the study and why. And it also becomes a recipe if you will for how the study will be conducted and how participants in the study can be studied safely. Once that's done, that protocol is reviewed for its scientific merit. That is just whether the question has been approached in a way that's scientifically valid and also for its safety by experts who really have no investment or part in the study itself, really two independent bodies. So the first step in conducting clinical research is to screen people who might be eligible for participation, for our group that means that people might call in to express their interest and we can talk with them about what's involved in being part of the study. Sometimes people email us and then we can get back to them in a phone call. After that we really hope to learn information about their child. So a trained clinician calls and speaks with parents about their child or children. And if that telephone screening seems to indicate that someone would be eligible or is likely to be eligible, then we invite them for a face to face visit here and do a more detailed review of their medical and psychiatric history in person. Then at the end of that day, we can say whether someone would be eligible for further participation or not. And then the last is that people enroll in an actual study after this screening. After they get an explanation, both in writing, something called a consent form, but also a conversation about that consent form. That allows them to ask questions and learn about what would be involved in doing the study and that process is called informed consent. So that's how we go forward when we think about any clinical research and certainly how the work here is conducted.

So the next thing I want to talk about is what is irritability? And why we study it. And what’s remarkable about this is how common irritability is as a symptom of psychiatric disorders. This is true for adults, but especially true for children and youth. In studies of adults that were done in the National Co-morbidity Study here, about 32 hundred adults were interviewed about their lifetime symptoms and behaviors and in that study about 10% of the general adult population reported having quite impaired irritability, to the point that it was interfering with their lives, at some point in their lifetime. So that's a really substantial chunk and what was interesting is that, of that 10%, 92% had other serious psychiatric disorders and by serious I'm talking about things like mood disorders. So things like depression or a manic episode. Or things like anxiety disorders or impulse control disorders or substance use, things that are major and impairing conditions. And so this one symptom of chronic irritability really is a connection to other serious conditions and not to be taken lightly. Another thing that we know is that in children, about 40% of those entering treatment in clinics, This Lamb's study (7:35) was a consortium of about ten different sites throughout the United States. And it was learned that about 40% of children coming in for psychiatric screening for help, had irritability as a primary symptom for their being there. And so we know that it's a major reason for children to request or be brought for psychiatric care. Despite this high frequency it's quite interesting that there's actually no official definition. In the Diagnostic and Statistical Manual that we use to understand psychiatric conditions, that word is never defined. And the concept may mean different things to different people. And so it's been one of the challenges of our work to create a usable definition, a way of measuring this. Another thing that we know about irritability as child and adolescent clinicians, is that we understand that irritability can be something that crops up in an ordinary way that it’s a part of everyday life, but it can also span a continuum up to a pathological spectrum where it really becomes impairing and quite out of control, disruptive to children's lives, disruptive in the settings where they attend school or after school activities, and disruptive to their peer relationships. And the last part about this is because we're child and adolescent types, we know that there's a developmental piece to irritability, that there are times in life, for example with toddlers or early to mid-adolescence, where irritability may be more prominent as a part of normative development. And so it takes on a different task under those circumstances. We understand that these times during life when one is trying to be more separate or establish their own autonomy, may be associated with greater irritability. But there are other times where it's less that case and we want to be sure that we don't begin to consider ordinary developmental stages to be signs of psychopathology. So we have to be thoughtful about that. So I guess the thing to say about how irritability demonstrates itself. We think about it as having these two features. One how it's sort of a constant in the background kind of touchiness a kind of a hair trigger that children live with and display, and in itself, this can be impairing. Children with this are described as being grumpy or easily annoyed or in a negative mood, easily triggered to become quite angry. And this can actually be a problem for their peer group or in the classroom. It actually can lead other children to want to avoid interacting with such a child because they always feel like the air is so tense around such an individual and parents often describe how they feel that they're walking on eggshells because there is this kind of negative, easily triggered quality. The other feature that really tends to be the more dramatic one are that they have these displays or flashes of anger where they explode. These may be verbal explosions and much more worrisome, physical explosions that are quite excessive responses to requests that parents make or that others make of them or events that don't go the way the child had hoped or disappointments that they face that are part of ordinary life. And these kinds of explosions often entail property destruction in children that are referred to us. They may lose friends as a result of these outbursts, really quite dramatic and negative influences in the child's life. There are really a number of disorders that display irritability. Sometimes people think that irritability really is a sign of just one condition, but we understand that actually irritability doesn't mean just one thing. If one walks through a variety of different diagnosis in the Diagnostic and Statistical Manual, one sees that there are: anxiety disorders, there are mood disorders, there are developmental disorders, things like attention deficit hyperactivity disorder, can all display irritability as prominent features. And so we don't think about it as meaning just one diagnosis and one has to really think about the pattern and other kinds of symptoms that are present in understanding that child and their irritability. I think the thing that I would want people to know is that irritability is very common and its impairing symptom is very common. Severe irritability isn't just a phase or a minor problem, its severe chronic irritability actually is a thing that can lead to greater problems and I'll have a little more to say about that in a few moments. It can be hard to describe and it can be hard to measure. Beginning to think about these dimensions of what the background looks like and how intense and frequent these flashes or explosions of anger are, can be helpful as a way of beginning to wrap one's mind around it. And that we're beginning to think about and study irritability much more than has ever been done in the past and to recognize how it may be key to understanding the impairment that some children face. So I'm going to shift gears a little bit and talk about bipolar disorder and the reason for this will become clear, I hope, very quickly. So in the Diagnostic and Statistical Manual. A manic episode is the thing that defines bipolar disorder and a manic episode in DSM-5 has a very explicit definition. There are first, the what we call "A" criteria and this really contains two different components. One is there are these qualities of mood. So an elevated expansive or an intensely irritable mood. And that during this time of elevated expansive or irritable mood there is also an increase in energy and what we call "goal directed activity". Being involved in some project in such a way that's quite consuming. This Mood should last for at least a week and when we think about it being present, we say it's present most of the day, nearly every day. So there might be some times where it's less intense, but really most of the day, most days is a way in which one can understand the presence of it's prominence. And it's easy for most people to grasp as a concept. How one has these "A" criteria, there also are what we call these "B" criteria. So once you establish that there is this problem of mood and increased energy. Then one begins to think about these other "B" criteria. And this underline section is what is a noticeable change from usual behavior is a new addition to the DSM-5, that was not present in DSM-4. These B criteria speak to changes in how one thinks about one self, so this inflated self-esteem or going out of bounds and assuming things about oneself that are not at all true. A decrease need for sleep, problems with pressured speech, as you can read for yourself. Flightive (16:43) ideas, moving from thing to thing very quickly without offering any sort of transition for people. Problems with really significant distractibility. Increased hyperactivity (16:58) and agitation which was noted above. This involvement in pleasurable activity without regard for their painful consequences. The key in these B criteria is that they occur either appearing for the first time or significantly worsening during the period of elevated expansive or irritable mood in the A criteria. So the way we talk about this is, is the B criteria appear or worsen during the episode, if you will, that's defined in the A criteria, they are bundled together. So the key and think about bipolar disorder is to compare the individual's functioning during an episode to that same person, to him or herself, when they're at their baseline or in their usual kind of day to day functioning, and one should see a dramatic difference. If you can't discern a difference, if the person's usual way of functioning is pretty consistent, then that would not be an episode. So what does this look like? Well, the example that I've offered here is sort of an amalgamation of two or three different children who've been in our studies. An un-medicated teenage boy who is in his early high school years is usually quite shy and very rule abiding, but during one week he has this period where his sleep declines quite significantly. He's only sleeping 4-5 hours a night instead of 8 or 8 1/2 hours which is typical for him. He has strange ideas and has this notion that he's writing three novels at once and with this time that he's not sleeping, he's up writing and writing and writing in notebooks and journals his ideas for these three novels that his composing all at the same time. He sneaks out of this room at night and goes out into the neighborhood because he imagines that he's on a mission in his neighborhood to troll for thieves or individuals that might be burglars, looking for bad guys and he's out much of the night on a couple of occasions during this week. Looking for bad guys unbeknownst to his parents. And he also describes that he has auditory hallucinations, this kind of strange description of he's hearing voices talk about rumors about him from the past. So with that as an understanding of what this looks like I want to say a little bit about this controversy of pediatric bipolar disorder as it's applied to children. And what we see here is dated that it was gathered from a very large national database of insurance claims these are outpatient insurance claims. And just to orient you (20:10) to the slide from 1994 to 2003 so roughly a ten year period. And here are on the Y-axis we have the percent of outpatient visits that are attributed to the diagnosis of bipolar disorder. From these hundreds of thousands of insurance claims over this period. And what's shown here in blue, is the rate of increase in outpatient visits attributable to bipolar disorder in adults 19 and older. And what you can see is that from 1994 until 2003, there was roughly a 60% increase in the rate of outpatient visits that were attributed to bipolar disorder. But here in red are for individuals 18 and younger and what you see here is a 4,000% that is 40-fold increase between 1994 and 2003 in the rate of outpatient visits that are attributed to bipolar disorder. This is a very substantial increase over a very short period of time and caused a number of us to scratch our heads and say "well, what do we think is going on here?" And it wasn't just in outpatient visits, but also in inpatient studies says the paper from Joe Ryder and Day (Dave?) Carlson produced and what they found is that for inpatient visits over roughly the same period. There was a 440% increase in inpatient diagnoses attributed to bipolar disorder and in this period for adolescents about a 300% percent increase. Again very substantial increases over very short periods of time. So the controversy comes up because we know that through the 1980's into the 2000's, in fact, even now, there are practitioners who are being invited to modify how the DSM-4 criteria have been applied to children and leaders during this period of time, leaders in our field and others said that you really can't or don't need to identify episodes, when it comes to making this diagnosis in children and adolescents. That you can begin to use this term bipolar disorder for conditions that were chronic, that is specifically those that were not episodic were they had symptoms of bipolar disorder or of a manic episode, but not in an episodic way. Now DSM-5 has come along and we know that making this modification is not correct. But it's very common that one finds clinicians who still think about bipolar disorder as this chronic condition and change in this is coming about slowly. DSM-5 is very clear that bipolar disorder is characterized by distinct episodes. But there are still people who imagine it to be a chronic condition. And so just to do a bit of a thought experiment, if you remove this episode criterion and begin to look at chronic illness and you allow yourself to double count symptoms, we can begin to see what might happen if you take a child who has attention deficit hyperactivity disorder and begin to think about their symptoms in light of a bipolar diagnosis and so for example where you have symptoms of being fidgety or getting up and running around or being on the go or acting as if you’re driven by a motor, well, that could easily be, if you will, translated into being psychomotor agitation as a symptom of bipolar disorder. Similarly, if you have trouble organizing yourself, you lose things, you’re easily distracted. Well, that could be distractibility as part of bipolar disorder, if you don't have to consider episodes. And when it comes to sleep problems in children with attention deficit hyperactivity disorder, this interesting study about 240 children with A.D.H.D. showed that about 74%, 73% of participants had problems with sleep about a third of them had mild problems. About 45% had moderate to severe problems with getting off to sleep, staying asleep or waking up too early. And this was their baseline functioning. And so we could say that children with A.D.H.D. have problems with sleep. And so if you stay on this line, these modified DSM-4 criteria for mania and, if you add in irritability and A.D.H.D. you can give it a new name. So if we start with these symptoms in red, that are very common in individuals with A.D.H.D. as their usual way of functioning, and we remove any requirement from foreign episode. And then as a second step we begin to compare those children to ordinary other children, not to themselves. And so if you begin to say well, If somebody has pressured speech and it's more pressured speech than an ordinary child would have rather than is this pressured speech greater or more severe for this child than they usually possess. If you start to compare to ordinary children, not themselves, and you add in one more thing which is this concept of irritability which may be more than a week, you can re-label individuals who have A.D.H.D. and irritability with the term bipolar disorder. A modified, if you will bipolar disorder diagnosis. And so we think that this may have accounted for part of that very substantial increase in diagnoses over this short period of time. And Ellen Leibenluft here really wanted to think scientifically about this problem and introduce the idea of severe mood dysregulation which has now found its way into the DSM-5 as this new phenomenon of Disruptive Mood Dysregulation disorder. So I thought that we should talk a little bit about that. Ellen's very smart notion was that we should use data to resolve this question about whether this broader definition of chronic irritability with A.D.H.D.-like symptoms was the same as the classic definition of bipolar disorder was to gather individuals and gather data that would help answer the question. And so that's what she set about to do, to bring in individuals who had what we call classic bipolar disorder. That is full duration episode of hypomania with elation or mania with elation. And then to compare them to children with something that was termed, Severe Mood Dysregulation chronic irritability with. A.D.H. D. like symptoms. As I showed in red in that previous slide. And that this should be really quite impairing to these individuals. So the first challenge was to create criteria for this more chronic irritable condition and then to use data to answer the specific question is this phenomenon of severe mood dysregulation the same as bipolar disorder? What kind of data would one gather to answer the question? Well, data about what becomes of such individuals, do they have a similar longitudinal course, whether their family histories would be similar. Because of course if they are similar conditions then the kinds of diagnosis and their families should be much the same and then of course the coin of the realm would be to look at the path of pathophysiology to look at brain functioning to see whether there were similarities in brain functioning. And I want to remind all of you that the criteria that we came up with were really created to answer this specific question. There was no design to create a new diagnosis, we just wanted to know whether this phenomenon of chronic irritability was the same as episodes of mania. So the diagnostic criteria that we created in concert with others from across the country were anger, sadness, or irritability and here you see this same expression, present most of the day most days and we also wanted it to be evident to those around the child and so what we said is that it had to be present in more than one setting. We didn't wish to be studying children who had problems exclusively at home where there might be conflicts with parents. We wanted it to show at school and with their peer group. We said they had to have hyper arousal symptoms, at least three of these six and you'll recognize that these are exactly like those symptoms in red that I had put up earlier. So things like insomnia, agitation, distractibility, racing thoughts, etc., and we also said that they had to have these explosive outbursts, what we call excessive reactivity and that we didn't want this to be a rare or infrequent phenomenon. We wanted this to be something that was regularly on the landscape of these children's lives. And so we said that they had to have at least three of these outbursts per week. We also said that it had to be chronic and so we defined chronic as present for at least the last 12-months in a continuous way. That way, individuals who might have just moved to a new locale and were having trouble settling in and so maybe for the first few months they were having a difficulty like this would not be the kinds of individuals coming into this study, but individuals who have these problems during the summer, during breaks from school, and during the school year. That it was a regular feature for them over an extended period. And the last because of the developmental considerations that we were talking about we knew that the children who were getting this modified bipolar diagnosis were typically young and so we want the onset to be before adolescence, we didn't want the kinds of conflicts that come up at home with adolescents and their parents that is so common, to be part of this diagnosis. And we also didn't want it to be for very young children. The kind of terrible twos or individuals in toddlerhood that were struggling. We also had scientific reasons, things related to our studies of the brain. Where we wanted to have children who were slightly older. And so we gave this age range of 7 to 17 for our criteria. So what this looks like, just as an example, this again is sort of an amalgam of other children who have been in our study. A 10-year old boy is described by his mother as angry all the time, arguing constantly. There's been aggression to property, there are holes in the drywall at home. Doors have been broken. The police have been called to the home three times in the last year to contain him. And I can say a little bit about how the police got involved, if people are curious. But he regularly hits and kicks his parents, he's bossy with his peers and as you imagine, based on this, has few friends. He fights with his friends at school, often. He entered on high doses of a stimulant and two of what we now refer to as these atypical anti-psychotic drugs, drugs that you may know by names like Abilify, Risperdal, or Seroquel and he's also on an alpha XXX (33:51) drug, something called Intuniv that was to help him with sleep. His first mental health contact was at age three. He also had a one week, three week hospitalization when he was nine years old and he's been on nine different medications in his young life. So already much like a chronic mental patient. And when he came to us, his diagnosis were bipolar disorder, A.D.H.D., anxiety disorder, and mood disorder, which certainly the mood part was very evident. So when you gather longitudinal data on individuals with this kind of problem, some very interesting things emerge. Melissa Broadman and our group and an individual at the group at Duke where the Great Smoky Mountains study was conducted. That published now on this very interesting epidemiological population. This is 1,400 children who were assessed starting at age 9, and they were seen at 11, 13, 18, and then again at 27 years of age. At a very high rate of keeping them in this study over time. These children were gathered because they belonged to a health maintenance organization. So they were coming for immunizations, well-child checks, they weren't showing up because they had psychiatric difficulties per se. The interviews for the Great Smoky Mountains study were coded and very useful way for us based on symptoms not just diagnoses. So we could find out how many children had insomnia, how many children acted as if they were driven by a motor, how many children had lack of pleasure in things. It would allow one to kind of go back and look at well if our severe mood dysregulation diagnosis existed at the time that these diagnoses were being made, what would they look like. And so we could say that the most common official diagnoses that came up in those with this proxy of severe mood dysregulation or anxiety disorders and what are called the disruptive disorders. Oppositional defiant disorder. Attention deficit hyperactivity disorder and conduct disorder. This is not especially surprising. When we think about these high levels of irritability. But it was quite surprising to us that a third of these children had no official axis one diagnosis. That means that they might be a symptom short or they might not have had all of the symptoms for a long enough period of time to get any DSM diagnosis and that there was no, if you will, diagnostic home for them in the D.S.M. manual at the time. And that would make it very hard to deliver services and to justify services for those children. We also saw that the prevalence of severe mood dysregulation in this sample was about 3%. Which is not a small number. But it's also not everyone. And so this underscores that this was really a significant problem and not one that, if you had two eyes and a nose, you would get. So based on this we could begin to look at the outcome data, what became of these individuals. And in the study that Dr. Broadman published when these individuals were 18, what we found is that individuals that have this proxy of severe mood dysregulation at 9 or 11, well, that predicted quiet highly that they would have major depression by age 18. And in fact our construct of severe mood dysregulation was a better predictor of having major depression at age 18 then if a child had depression at age 9 or 11. So just to say that SMD was a more robust predictor, major depression at age 18 than depression at 9 or 11 was for depression at age 18. The other is that not any of these cases develop bipolar disorder in the Great Smoky Study by age 18. And then. Dr. Copeland published data on individuals now at age 27 looking at the construct of D.M.D.D. as it is in the DSM-5 and found that, depression and anxiety disorders, in 27 year olds were predicted by D.M.D.D. And they also found in the study. That there was a very high rate of other diagnosis in this population and that they had a very poor functional outcome. That is occupational, marital, social functioning, visits to emergency rooms were all greatly increased. In this D.M.D.D. population by age 27. And in our own studies here, where we begun to gather individuals, we had individuals with classic polar disorder and those with this constructive mood dysregulation. And we could follow them over a period of time and so our dearest XXX (39:37) published this paper in 2010, looking at a follow up of 28 months. And what we found is the rates of having a hypomanic or a manic episode were very different in these two populations. Among those with classic bipolar disorder, about 63% had a hypomanic or manic episode within this 28 month period. Whereas those with severe mood dysregulation about 3% had had a hypomanic or manic episode. This is a very big difference. And what we've found is that the rate of bipolar disorder among those with severe mood dysregulation was about the same as the general population prevalence of bipolar disorder. Their risk for developing bipolar disorder did not seem any greater than anyone in the general population. So it wasn't a forerunner if you will, of later bipolar disorder. So we gathered from this that children with severe mood dysregulation, don't go on to develop bipolar disorder. They didn't in the Smoky Mountains Study, they didn't in our follow up studies. They haven't in other studies and that severe mood dysregulation isn't a prelude to bipolar disorder. So to say about this problem of behavioral disorders something else that we've learned, those with. A.D.H.D. and oppositional defiant disorder, it seemed to be called behavioral disorders or disruptive disorders. It's not just about behavior, It's also about their emotions and their mood and that there is a mood component here that we need to pay attention to and it raises the question about whether treating these mood problems could be critical in helping these individuals and may be important for their overall outcome. So just to say severe mood dysregulation is really common, about 3% of the population that it predicts depression and the displaying severe irritability isn't sufficient to make a diagnosis of a manic episode. Really to make a diagnosis of a manic episode, you require a lot of other symptoms. What we learned about family history, again Dr. Broadman had published a study in 2007 where we had a unique opportunity. We could bring parents of bipolar children into the NIH and have them go through a very careful psychiatric interview and compare the diagnosis that those parents received, to the parents of individuals of children with our constructive severe mood dysregulation. The interviewers conducting these interviews were blind as to the child's diagnosis, so they wouldn't know if this was someone who was a parent of a bipolar child or the parent of a child with severe mood dysregulation. What we saw was that there was an eleven times greater rate of bipolar disorder in the parents of bipolar children compared to the parents of severe mood dysregulated children. This is a very big difference. And the rates in the parents of children with bipolar disorder was about a third. And the rates of bipolar disorder in the parents of children with severe mood dysregulation was about 3%, again, that general population prevalence. What's fascinating is that Bipolar disorder was the only diagnosis that showed this dramatic difference. Anxiety Disorder, Substance abuse disorders, and other mood disorders, were not different between parents of children with bipolar disorder and parents of children with severe mood dysregulation. And as I said, the rate of bipolar disorder in the parents of severe mood dysregulation was about the same as the general population prevalence. So if we move to the biological and physiological features that we're so keen on understanding. We're using this technique of Magnetic Resonance Imaging, which has both functional and structural capacities. And this is a lovely animated picture drawn by one of our 10 year old participants about her experience in the scanner. And while triggering her in the M.R.I. scanner we can ask them tasks or ask them to perform tasks where there may be emotion information, like looking at this face and asking about how hostile this person appears or how afraid they are or asking them about physical features that would just bring their attention to the face without asking about any emotion responses, like how wide is this person's nose? And what we found through these kinds of studies is that there are quite substantial differences in the brain circuitry between individuals with severe mood dysregulation and those with bipolar disorder. This is a kind of a smattering of some of the things that we've discovered. Gender identification tasks, looking at different kinds of faces. Show differences in these two populations. Their capacities to respond flexibly to changing information is different between severe mood dysregulated and bipolar children and the ability to stop a motor response when given a signal has different features and different circuitry between these populations. So just to say that we'd seen physiological changes. Changes in longitudinal history and changes in, if you will, in family history between these two different disorders. So there's some diagnostic and treatment implications that shake out from these differences. One is, as I've said, that the data shows that these severely chronically irritable children really differ from does from bipolar disorder and their outcome, their family history, and in their brain mechanisms. DSM-5, when it was being constructed. The committee for DSM-5, recognized this and was concerned about the lack of that diagnostic home and so created this construct of disruptive mood dysregulation disorder that is now in the DSM-5, these are the criteria. And you'll see how similar they are to our criteria for severe mood dysregulation. Severe recurrent outbursts that are not consistent with that individual's development. They occur on average three times a week or more. The quality of irritability is present most of the day most days. It's present for 12-months, at least in a couple of settings. They said not before six and they had some exclusionary criteria such as autism spectrum disorders, post-traumatic stress disorder and others. So just to say that this constructive D.M.D.D. isn't exactly the same as S.M.D., they are similar, but not the same. They both show irritability. They both have an early age of onset. They both suggest significant impairment. But D.M. D.D. has an earlier age of onset requirement than we placed. D.M.D.D. did not require the hyper arousal symptoms that we've listed. And that D.M.D.D. if you will, trumps, that is, if you have oppositional defiant disorder and D.M.D.D. That's just D.M.D.D. whereas when we were doing this we said that you could have oppositional defiant disorder and severe mood dysregulation. So the implications for treatment are that if this is not the same as bipolar disorder and I hope that I've given you some thoughts that it should not be the same as bipolar disorder. Then that opens up the possibility of treating it differently than the way one treats bipolar disorder. One, perhaps severe mood dysregulation should be thought about more like A.D.H.D. with anxiety or A.D.H.D with depression And if so, what one would be encouraged to do, would be to treat what's there. That is to use stimulants like XXX (48:14) something called Ritalin or XXX (48:15) or dextroamphetamine, things like Aderrall or XXX (48:21), to treat the A.D.H.D symptoms and then to add in treatments for anxiety or depression. Such as, medication like seretonin reuptake inhibitors or cognitive behavior psychotherapy or a combination of these to treat those symptoms. But you wouldn't think about using an S.S.R.I. and a stimulant to treat something like bipolar disorder, for example. So there's a lot we don't know about the treatment of it and in fact we've been working into this quite vigorously. We conducted a study of lithium carbonate in children with severe mood dysregulation and found that it was no more helpful than placebo. But we have discovered that on our inpatient unit environmental interventions can be very powerful and really quite impressive, in the effect on children and were beginning to think more about what is the component of those environmental interventions that are so powerful and helpful. We also had been engaged and are currently engaged in a study that looks at the benefit of stimulant medication plus a serotonin reuptake inhibitor versus stimulant medication plus a placebo. And as that study becomes more further along as we are able to look at the data more closely, what we may be able to offer an answer about that particular combination for this problem. And we begun to focus now a lot on non-pharmacological treatment because we've recognized how important these may be. So I'd like to say a little bit about assessment tips and guidelines. When thinking about children who have a problem like disruptive mood dysregulation disorder or bipolar disorder, it’s advisable to interview the parent and the child separately. It's very hard for children to sit by and listen to their parents pick off a list the things that they couldn't do, didn't do, wouldn't do. It’s very hard to sustain a rapport with a child who's had that kind of experience. So what we do is we separate the parent and child. Talk to each individually to get their take on what's happened. And then we can bring them together later to say well you know you said this and you said that, help us understand this. Help us understand what may be a more accurate picture. And we find that they can cooperate actually fairly well in that much of the time. We like to look at the presence of the symptoms across different settings, so we ask at home, what it looks like in school, what happens with peer relationships. And where we are thinking about bipolar disorder, I hope that I've made the point that it's really all about the episodes as Dr.Leibenluft often says. Are there episodes where the individuals clearly different from their usual functioning? Or is this a really steady presence of irritable mood? In which case that would suggest disruptive mood dysregulation disorder. If any episode, symptoms change in this bundle, they change or occur together with other symptoms. They don't have a life of their own, they don't have their own kind of role, it's there during the episode but it's also there outside of the episode. And that we expect that the mood will show changes across different settings. We've had people ask us whether somebody can have mania only at home. One would expect that if one was having a manic episode that it would show at school and with peers. We want to be developmentally and culturally sensitive, and so this is pretty tricky. When you have elevated mood or grandiosity. You want to think about what the individual's developmental level is. Fantasy and fantasy play is something that developmentally younger children do and is not considered grandiosity. Also, there are cultural considerations how people think about themselves, particularly religious kinds of feelings. How they view their relationship with God and when one is outside of a cultural group. Those kinds of things can be misunderstood and should not be labeled pathological. Sometimes words can be ambiguous and we've had parents say that their child acts as if the rules don't apply to him. Sometimes that can be a really significant departure for that child as it was in the example that I gave you of the adolescent with bipolar disorder. But sometimes it's also just a kind of a snarky, arrogant attitude that adolescents can display with their teachers. And also to say that difficulties with getting to sleep. It's not the same as a decrease need for sleep. The decreased need for sleep means that you still have really good energy, even when you’ve gotten three or four less hours of sleep at night, for a few nights. When we're thinking about D.M.D.D. we want to look for a routine pattern of these outbursts at home, school, and with peers. We want to think about what that child's mood is like when they're not having an outburst. We think carefully about their developmental level. And we want to consider how parents and others make accommodations for their children. Because often walking around on eggshells prevents these outbursts. But it means people's lives are severely constricted. They really are impaired. In many many aspects of their lives and in the family's life. And so this is a flyer that just describes how people can contact us if they have questions or wish to know more about the work that we're doing or even if you just have questions about disruptive mood dysregulation disorder or bipolar disorder. Here's a phone number that people can use to reach us. And here is an email address where people can write us and we will contact you to answer questions that you've got, and perhaps to be helpful to you if we can. So I think I'll stop here, we have a little bit of time for questions. If people could type questions into their chat box, that would be helpful and I'll try to answer to the best of my abilities.

So what someone has written in asking about is examples of environmental interventions. So some of these sound quite logical. But it's remarkable how effective they can be. During the time that a child may become frustrated, we are on a campaign to get children to start to tell us that they're beginning to feel angry before they show us that they are angry. We think that children being able to leave the physical surrounding that they are in to go to a place to talk with someone is quite effective that physical distance can allow them a chance to kind of calm down or chill out. We've found that being able to listen carefully to the kinds of things that they find difficult or challenging can actually allow modifications that are affective for them and that they learn when they can engage in these kinds of conversations that they don’t need to explore or destroy things in order for people to listen or understand them. We've also learned that many of the kinds of things that lead to explosions are really based on problems with information processing and executive functions. And so putting in interventions that support them in those ways will also reduce the intensity and frequency of their outbursts. Someone's asked about emotional intelligence kinds of training and this would be exactly the kinds of things that we would be thinking about. We're beginning to do work here to think about a kind of cognitive behavioral therapy that might focus on giving kids a chance to practice being in situations with frustration and developing coping strategies with their therapist that would assist them in managing those kinds of events and practicing them. We also have been looking at some tasks that are computer-based training helping them with interpreting faces and improving the accuracy of their read on the emotions that faces display because many of our are participants have problems in accurate face-emotion identification.

So the question was therapeutic intervention that would be available for parents who refuse to give their children medication or perhaps are too afraid of medication to give them to their children. And I think that the work that we're doing here now offers examples of the kinds of things. I wish that I could tell you that work was far enough along that we would be able to distribute it and begin to do field testing of it, but it's very early in that work, but these kinds of things like looking at cognitive behavioral therapy that one would use for anxiety or depression hopefully the cognitive behavioral therapy that we're starting to work on, specifically related to irritability and aggression or some of these kinds of things related to improving the accuracy of one's read on faces and emotions can also be quite helpful to children something that sometimes is referred to a social skills but really a much more specific part of that social skills learning XXX (59:16).

Really interesting question about the rate of comorbidity in bipolar disorder, compared to the rate of comorbidity with A.D.H.D. in our constructive severe mood dysregulation. So I can tell you that among our children with severe mood dysregulation about 60 to 66% of the children in our severe mood dysregulation cohort have comorbid A.D.H.D., so it's quite high. It’s a little hard to give figures for bipolar disorder because of the way in which the modification and the criteria created this blurring and so it would be, Well, whose definition of bipolar disorder. The rate of A.D.H.D. in classical bipolar disorder in children is higher than in the general population. It may be around a third, maybe 40%, but there are some studies where it's been as high as 85% or 90%. Again depending on how broadly those DSM-4 criteria for bipolar disorder were interpreted.

Oh, I love this question whoever wrote in saying, Is brain imaging helpful for diagnosing either of these conditions and is it becoming a standard practice? Thank you for writing that question, the answer is no. So just to be clear, there is no specific pattern that would allow one to make a diagnosis of either of these conditions based on magnetic resonance imaging or functional magnetic resonance imaging. And we are way too early in the game to be able to use this as a diagnostic procedure. What we're hoping to learn is about brain functions in these conditions and hopefully to inform treatment interventions based on our understanding of brain function that comes from this work. So someone has asked about whether supplements, will say complementary or alternative medicine that might be given to children because a parent might be fearful of using prescription medication. And I think at this point, there really aren't any supplements or complementary or alternative medicines that could be recommended based on any studies that have been done. That would be scientifically rigorous studies. One of course sees anecdotal reports, certainly looking at blogs and we see parents and talk with them. I know that many have tried omega-3, have tried vitamin supplements and other kinds of things. But really there isn't any systematic study of these in children with severe mood dysregulation or with bipolar disorder that would allow one to recommend them. Yes, someone asked how was it that the police became involved with the young man in the sample, and the issue here is that the level of aggression, children like this can display at home can be frightening to siblings and parents and parents sometimes may move to begin to restrain their children or hold them until the explosive outburst has passed. But this can raise concerns when a child appears at school or in a therapist’s office with bruises or marks on them from being heavily restrained by a parent. And of course there's always the concern about whether such a child is being abused, so clinicians annotation will recommend that when a child loses control to such a degree, that people at home are frightened, that the police should be called and that would provide another intervention and protect the parents against being seen by child protective services as abusing or behaving in an overly aggressive way toward their child. And that's exactly what happened in this case. The parents were following the direction of the therapist for the child in calling the police when things had reached that dangerous level. I want to thank everyone who's asking for copies of this PowerPoint. If you wish you can write XXX (1:04:02) who is my wonderful co-worker in this experience and she can send you hard copies of what we've put up here. We don't send electronic copies, but we would be happy to send paper, hard copies to those that ask. So I think we've come up to our time. I can't thank you all enough for giving us your attention over this time. We will be doing webinars going forward. And, so if this has been helpful to you, I want you to kind of send XXX out about that. Also if it hasn't been helpful or if there are things you think we need to speak about in a different way, I would appreciate that feedback. It's really a great help to me to hear feedback from all of you about this kind of material. So thank you very much for tuning in today.