Disruptive Mood Dysregulation Disorder Revisited

In the brief history of this blog, the post where I shared my thoughts on DSM-5's disruptive mood dysregulation disorder (DMDD) has gotten by far the most pageviews. It's been almost two years since I wrote that post, and I would like to revisit DMDD with some updated thoughts on this diagnosis.

As you may recall, DMDD sprang out of a desire to have a diagnosis other than "bipolar disorder" to describe children who are chronically irritable and have explosive tantrums. Almost all of the children with DMDD also meet the criteria for oppositional defiant disorder (ODD) and are at higher risk of developing depression but not mania. The NIMH researcher Ellen Leibenluft, whose work on severe mood dysregulation (SMD) strongly influenced DMDD's creation, had commented in the past that she was not 100% sure that DMDD was a good idea.

In the last few years, I have only seen a handful of children who met the criteria for DMDD. Here is what I noticed in my own practice:

• One boy was being raised by a single mother who worked full time, so his grandparents were very involved in childrearing. The mother tried to set rules, but the grandparents were much more permissive, and whenever the mother tired to enforce her rules, explosive tantrums resulted.
• Another boy was very violent toward his mother on an almost daily basis. His father was home but did not intervene, while the mother had anxiety and literally appeared fearful of her son during their visits with me. When he hit her, she would tell him verbally that it was wrong, but did not do anything else (like using a time-out) to try to change his behaviors.
• There was a girl (who I'd written about previously) whose mother was very emotionally distant and pulled away further every time the girl acted out because the mother was reminded of her own emotionally intense mother. This distancing seemed to lead to the daughter becoming even more irritable.
• And then there was a boy who was extremely aggressive at home, constantly fighting with his 3 siblings. The household was very chaotic, with parents still married but frequently arguing with each other. Both parents often resorted to spankings, which did not seem to decrease the boy's aggression or irritability.

Certainly, correlation between the parental characteristics and the children's behaviors does not tell us about causation. It is very stressful raising irritable, explosive children, and the children described above definitely had intense, strong-willed temperaments. My intuition is that it's an interactive process where both parental and child characteristics trigger maladaptive behaviors in each other that escalate over time. But are these families typical of cases of DMDD? I searched Pubmed for "disruptive mood dysregulation disorder" and found 20 papers published in the last 2 years (out of 29 total).

Of the 20, most were reviews/commentary, and only 6 papers were original research. One was a brain imaging study looking at "neural mechanisms of frustration in chronically irritable children." Another examined the prevalence of SMD 2 and 4 years out from initial diagnosis, and found that 40% still met full criteria at 4 years, but a significant number not meeting the criteria were still moderately impaired. Another study from Duke's developmental epidemiology program used a large database to examine the adult outcomes of those who would have met DMDD criteria as children and found higher adult rates of depression, anxiety, adverse health outcomes, impoverishment, police contact, and lower educational attainment.

To my pleasant surprise, there were actually several papers that included data on family characteristics of children with DMDD. The first was a cross-sectional study of a community sample of 6 year-old children, which found that 8.2% of them met DMDD criteria based on a structured interview of parents. Impressively, the study examined 6 domains ("demographics; child psychopathology, functioning, and temperament; parental psychopathology; and the psychosocial environment") for correlates of DMDD. The parents were also interviewed about what things had been like when their children were 3 years old, and here's what the researchers found:

The age 3 years predictors of DMDD at age 6 years included child attention deficit hyperactivity disorder, oppositional defiant disorder, the Child Behavior Checklist - Dysregulation Profile, poorer peer functioning, child temperament (higher child surgency and negative emotional intensity and lower effortful control), parental lifetime substance use disorder and higher parental hostility.

The second study was a prospective one that "followed 317 high-risk children with early externalizing problems from school entry (ages 5-7) to late adolescence (ages 17-19)." The children sorted into 3 groups by the time they were adolescents: one group with conduct/criminal problems and anger, one group with mood dysregulation, and one group with a low level of symptoms. The authors found that generally, those who were more overtly aggressive as children tended to have conduct problems as adolescents, while more emotionally dysregulated children had more mood dysregulation in adolescence. The key finding:

For children with early emotion dysregulation, however, increased risk for mood dysregulation characterized by anger, dysphoric mood, and suicidality - possibly indicative of disruptive mood dysregulation disorder - emerges only in the presence of low parental warmth and/or peer rejection during middle childhood.

Another study (with 13! authors) was published in a much more prestigious journal than the previous 2 papers, and to me it was the least enlightening. The study examined the risk of DMDD in offspring of parents with bipolar disorder and found a much higher risk of DMDD (odds ratio = 5.4 "when controlling for demographic variables and comorbid parental diagnoses") compared to offspring of control parents. Given what those two other studies found, I'm not surprised that parents with bipolar disorder, one of the most severe psychiatric illnesses, would have children at risk of DMDD.

One last noteworthy paper that turned up in my Pubmed search is a recent article on whether DMDD should be included in ICD-11. The International Classification of Diseases is the World Health Organization's standard system for classifying every health problem imaginable, and the 11th revision is due in 2017. Even in the U.S., the ICD diagnostic codes are the standard for coding and billing purposes, and each DSM diagnosis is mapped to a corresponding ICD code. In this paper, the authors, who were members of a task group convened by the WHO to provide recommendations on the classification of disruptive behavior disorders, wrote:

The task group has recommended that WHO not accept DMDD as a diagnostic category in ICD-11, but rather approach the issue in an alternative, more conservative and more scientifically justifiable way. Specifically, the group has proposed that ICD-11 include a specifier to indicate whether or not the presentation of ODD includes chronic irritability and anger. We believe this option provides the most parsimonious basis for identifying and appropriately treating children with this maladaptive form of emotional dysregulation.

In my previous post on DMDD, I thought that it was overall a positive step away from the rampant over-diagnosis of pediatric bipolar disorder. But I did not end up using it; I was not about to diagnose those children with bipolar disorder in the first place. Thus, I find myself agreeing with the WHO task group. With ODD, the standard first line treatments are interventions that help parents better manage their children's behaviors and/or improve the parent-child relationship. I still worry about drug companies trying to market a medication for DMDD that supposedly targets a problem in the brain of the child. Thankfully, at least Abilify hasn't been approved yet for treating DMDD and hopefully never will, having gone off-patent this year.

Psychiatry as a Clinical Neuroscience, Why Not?

I first heard the term "clinical neuroscience" used in relation to psychiatry as a resident in 2009, when my associate program director handed out a paper to us trainees titled: "The Future of Psychiatry as Clinical Neuroscience." She presented this as a ground-breaking document that would greatly influence the rest of our careers. Shockingly, the authors of that paper did not cite NIMH Director Thomas Insel, who had an earlier article in 2005 titled: "Psychiatry as a Clinical Neuroscience Discipline." Since then, Dr. Insel has posted an updated version of the article on his blog (publication date: unknown) and wrote other blog posts championing the notion that in order for psychiatry to advance, we must focus on basic neuroscience research. And now, a recent article asks, "The Future of Psychiatry as Clinical Neuroscience: Why Not Now?"

The authors, who are program (or associate program) directors of residency training at Yale, Pitt, and Columbia, bemoan the fact that advances in understanding mental illness based on neuroscience research have not made their way into clinical practice. As barriers, they cite "the pervasive belief that neuroscience is not relevant to patient care," as well as the complexity of the research. They argue that the best place to start enacting this paradigm shift is in psychiatry residency programs right now. They also write:

The diseases that we treat are diseases of the brain. The question that we need to address is not whether we integrate neuroscience alongside our other rich traditions but how we work as a field to overcome the barriers that currently limit us. Ultimately, the most powerful force will be the improved translation of research into more refined explanatory models of psychiatric pathology and into novel therapeutics. To ensure that our field is ready to embrace new findings as they emerge, we need to begin the process of culture change today by enhancing communication and collaboration between researchers and practitioners.

I think 1BOM hit the nail on the head when he wrote: "Rather than being 'ready to embrace new findings as they emerge', tomorrow’s psychiatrist needs to know how to critically evaluate new findings as they emerge [italics in original]." I remember being taught as a resident about Broadmann Area 25 being critical in the pathogenesis of depression, based on exciting initial deep brain stimulation results from Dr. Helen Mayberg. This was almost treated as an established fact, despite the very preliminary nature of the research. Well, what happened when they tried to do a larger clinical trial? Neurocritic reported that the trial was halted before its planned endpoint in December 2013, and last month it was revealed that the medical device company conducting the trial (St. Jude) stopped it due to perceived study futility.

Do the clinical neuroscience curriculums for psychiatry residents teach the importance of humility and emphasize just how much we don't know? One of my favorite articles in the past year has been Tom Stafford's BBC Neurohacks column from December 2014 in which he discussed the importance of redundancy in the brain. He described the case of a woman who, despite missing her entire cerebellum, was able to live a fairly normal life:

This case points to a sad fact about brain science. We don't often shout about it, but there are large gaps in even our basic understanding of the brain. We can't agree on the function of even some of the most important brain regions, such as the cerebellum. Rare cases such as this show up that ignorance. Every so often someone walks into a hospital and their brain scan reveals the startling differences we can have inside our heads. Startling differences which may have only small observable effects on our behaviour.

Part of the problem may be our way of thinking. It is natural to see the brain as a piece of naturally selected technology, and in human technology there is often a one-to-one mapping between structure and function. If I have a toaster, the heat is provided by the heating element, the time is controlled by the timer and the popping up is driven by a spring. The case of the missing cerebellum reveals there is no such simple scheme for the brain. Although we love to talk about the brain region for vision, for hunger or for love, there are no such brain regions, because the brain isn't technology where any function is governed by just one part.

 As Neuroskeptic recently tweeted:

Neuroscientist: someone who knows how little we know about the brain.
— Neuroskeptic (@Neuro_Skeptic) March 28, 2015

This is a point that needs to be made and repeatedly emphasized to those who write things like "the diseases we treat are diseases of the brain." The irony for me is that I do appreciate the importance of neuroscience in psychiatry and agree with the authors when they wrote: "The more sophisticated and nuanced our science becomes, the more critical it is to have individuals who can translate this work to make it accessible to students at all levels." It reminded me of one of my favorite college classes, Principles of Neuroscience. The professor, who studied ion channels in different animals, was an amazingly good teacher, and the first lecture started something like this:

"Ernest Hemmingway once boasted that he had a six-word story—complete with beginning, middle, and end—that would bring tears to anyone who heard it. Here it is [he lowered the lights in the room and said the following words softly and slowly]: 'For sale…baby shoes…never used.' [dramatic pause] While not all of you are tearing up, very few people could have heard those words without thinking of or feeling something. Any images in your mind (did you see the shoes, what color were they?), any thoughts or emotions you may have experienced after hearing those six words, formed as signals in your nervous system. Without the nervous system, we cannot see, hear, feel, taste, or smell—in short, our five senses would produce no corresponding thoughts, and life as we experience it does not exist."

The tour de force lecture progressed to descriptions of single neurons and how our nervous system is comprised of approximately 100 billion of them, each of which can have tens of thousands of synaptic connections to other neurons. The quote I remember most clearly: "All of the neurons together in one brain form more connections with each other than there are stars and planets in the galaxy." The professor ended his lecture by giving us some practical tips based on his knowledge of neuroscience. Time and repetition, he told us, is what will help us succeed in the class, because that is how neuronal circuits are programmed and how processes in the brain ranging from retrieving facts from memory to riding a bicycle become automatic. I use the same advice almost daily with my patients when I emphasize to them the importance of practicing new behaviors or ways of dealing with difficult thoughts and emotions. Similarly, based on my reading of research on the effects of sleep, exercise, and social interactions on the brain, I share with my patients the importance of getting enough of each.

I learned more neuroscience of clinical relevance in one semester from this PhD Biology professor than I have from years of attending lectures and reading papers from psychiatry researchers who are considered world experts in areas like the neurobiology of OCD, pediatric bipolar disorder neuroimaging, or how transcranial magnetic stimulation affects neural circuits in depression. For me, the most important distinction when we talk about clinical neuroscience is whether we take a broad view of neuroscience or a narrow view. The broad view would emphasize the huge effect of all of the different inputs on the brain (e.g. that six words can bring a person to tears), whereas the narrow view tends to emphasize things like genetics, neurotransmitters, biomarkers, and circuits.

The Tragedy of Palo Alto

Sorry for the long absence. I'm going to try to shake off the winter doldrums and resume blogging semi-regularly.

Palo Alto, CA (est. 2013 population: 66,642) is one of the wealthiest cities in America, with nationally-ranked public high schools, quiet tree-lined streets, and exceedingly low crime rates. Since 2000, the city has averaged about 1 murder per year. Sadly, that number has been dwarfed by the number of Palo Alto teens committing suicide every year.

In 2009, Palo Alto gained national notoriety when a cluster of suicides occurred amongst students at Henry Gunn High School. The attention-grabbing nature of the suicides (most occurred by jumping in front of an oncoming train) and the relative ease of access to the suicide method likely contributed to subsequent suicides. The national youth suicide rate is about 10 per 100,000 per year, so any suicide in a district that has several thousand high school students is a cause for concern. Multiple suicides in such a short span of time understandably led to alarm.

At the 2011 AACAP meeting in Toronto, I attended the session Teaching the Community in Times of Crisis: Responding to Teen Suicide. The main speaker (Madeline Gould, MPH, PhD) was very informative and presented a wealth of research-based data emphasizing how suicides can cluster and spread, while media reports on the suicides can either help or hurt the situation. Dr. Shashank Joshi, a psychiatrist at Stanford, discussed the school-based suicide prevention program that Stanford helped the Palo Alto school district put in place after the suicides. The program has similarities to public health approaches designed to combat disease outbreaks: There are efforts to decrease stigma, provide education about depression how it can lead to suicide with emphasis on the effectiveness of available treatments, train teachers and parents to recognize signs of depression, teach coping skills, and identify vulnerable teens through screening and then making appropriate referrals. From what I gather, this program is still in place, and Dr. Joshi just published an article titled School-Based Suicide Prevention: Content, Process, and the Role of Trusted Adults and Peers, with one of the key points being: "Prevention efforts must focus on school-based mental health education and promotion."

What was not addressed at the AACAP session was what may have been happening at the community level that was triggering the suicides in the first place. Given the relative rarity of suicides, it is hard to prove what causes each suicide or how effective current school-based prevention methods are. Unfortunately, what we do know is that suicides amongst Palo Alto students are still occurring, with another one earlier this month, bringing the total to 3 for the year.

In this past week, Palo Alto Weekly has published two opinion pieces, one by Palo Alto psychiatrist and parent Dr. Adam Strassberg, the other by pediatricians from the Palo Alto Medical Foundation. Both are worth reading in full, because in my opinion they make a valiant attempt to get to the root of the problem. Neither one mentioned anything about screening for depression or increasing access to mental health care. Dr. Strassberg emphasized the pressure that parents place upon their children to succeed:

We are so many of us wealthy and secure beyond imagining, and yet we have such enormous anxiety. We fear the future harm that we will lose our wealth and privilege and be unable to pass it on to our future generations. Maintaining and advancing insidiously high educational standards in our children is a way to soothe this anxiety.

But it harms our children.

The pediatricians make a similar point:

While we are not education specialists, as pediatricians we do recognize dangerously unhealthy lifestyle patterns and habits that are known to exacerbate stress, anxiety, depression and physical illness. These include chronic sleep deprivation, lack of unscheduled time for thought and relaxation, unhealthy eating habits, lack of exercise and unrealistic pressures (real or perceived) to achieve. Those unrealistic pressures include excessive homework, overly ambitious course loads and a seeming demand for perfection in grades, sports and extracurricular activities.

We see these problems day after day in our teen patients. We believe there are specific factors that could be targeted for change.

Sleep: Surveys have shown that Palo Alto teens sleep an average of 6.5 hours per night. Studies have shown that teens need 9 hours of sleep to function at their best. […]

Six-and-a-half hours of sleep, average. So for every teen sleeping 8 hours a night, there's one who's only getting 5. I know that I feel grumpy and foggy even with 7 hours, so it's hard for me to imagine what these teens are going through. I'm not saying that the school-based mental health programs are useless, but it's clear as day to me that they do not go far enough up the chain of causality to address the most important factors leading to all of these adolescent suicides. And it's not just Palo Alto, but achievement-driven communities everywhere, that have this problem. Hopefully, more professionals will start engaging families in a discussion of these root causes, rather than only trying to treat surface symptoms.

Like Water

The flustered mother told me this about how difficult it was to get her school-aged son to do what she wanted: "He's like water. Whatever I try to do, whatever rules I set up, he finds a way around them."

I said, "Well, that must be very frustrating."

Here's what I wish I had been clever enough to say to her instead: 

"You're right. Kids are a lot like water. The harder you try to grab them, the more they slip through your fingers.

Like water, kids can mirror their surroundings. They are given shape by their environment, while over time they are also shaping the environment.

Similar to water, kids can exist in different states. Too much heat or too much cold, and they may become explosive or get more rigid and brittle.

Water is very resilient. Most of the time, like water, kids can return to their previous state after a perturbation if the environment allows it.

It always takes energy to change the flow, the direction, the trajectory of water. Otherwise it just follows the path of least resistance.

Just as you can make water move against gravity through capillary action, giving the right scaffolding for a child can make all the difference. 

While water running rampant can be destructive, water put to purpose can do immeasurable good.

So you're absolutely right: your child is very much like water. Now what shall we do about it?"

Why I Love Wall-E (and Question the ACA)

Spoiler warning: If you haven't seen Wall-E yet, why not? See it first before reading this post if you don't want certain aspects of the plot revealed.

Let me tell you why Wall-E is my favorite Pixar move. The title protagonist begins the movie as a humble robot, programmed with a very specific purpose: to pick up garbage, compress it, and stack it in neat, towering piles. In Wall-E's world, man-made trash overwhelmed the earth generations ago, smothering all plant life. The humans escaped in giant spaceships, leaving robots behind to clean up the mess. Over time, all of the other robots broke down, with Wall-E the sole survivor living a repetitive, lonely existence. Yet Wall-E somehow transcends his programming and develops a sense of curiosity about the world. What were those humans like? What are these relics that they left behind? What's that green thing growing amongst the trash?

After a series of improbable but exciting events, Wall-E finds himself on board one of those giant spaceships. There, he encounters real, live humans and the robots that serve their needs. The people were uniformly plump with adiposity, reclining comfortably on mobility chairs while sipping futuristic Big Gulps™ and fixated on screens. Wall-E was aghast, eventually discovering that the villainous AI of the ship was trying to keep the humans confined to their blissful but vacuous existence. Wall-E finds a way to rally the other robots and spread the news that plant life was growing on earth once again. The movie ends on a hopeful note, with the ship returning home and the humans taking small, earthbound steps that feel like giant leaps. I love that Wall-E acted in humanity's long term interests instead of either rejecting these disappointing humans or attending only to their short term comfort.

Recently, I was reminded of Wall-E when I attended a session at AACAP's Annual Meeting in San Diego titled: "The Affordable Care Act [ACA] and How We Think About Systems, Care, Quality, and Ethics." The discussants covered various aspects of the ACA (for an overview of the ACA, see this recent post from Psych Practice). What interested me most was the talk by Dr. Michael Houston on how the ACA relates to child and adolescent psychiatrists. Dr. Houston discussed the ethical underpinnings of the ACA, namely how it seeks to institute a more egalitarian and less libertarian health care system. The law lays the groundwork for transitioning us from a fee-for-service system in which doctors have a financial incentive to do lots of procedures to a system in which both patients and doctors have a responsibility to society to contain costs.

Clearly, one of the goals of the ACA is to make doctors provide more efficient care. One of the justifications for why we need this is the chart above (from this HuffPo article) showing how, despite spending way more than any other country on health care per capita, the U.S. trails most other developed nations in life expectancy. The logic seems to be that since we're not getting good bang for our buck, the health care delivery system must be streamlined.

This focus on efficiency would have an especially high impact on child psychiatrists, given how relatively few of us there are compared to the high numbers of patients. Here's an old article from 2006 about the shortage, and not much has changed since, except that even more children are being diagnosed with conditions like ADHD and taking multiple medications, putting further strains on the health care system. Last year, AACAP published a document describing how the ACA will impact the practice of child and adolescent psychiatry. More mental health care will be delivered by pediatricians and care managers, with psychiatrists overseeing cases but not seeing patients directly unless they were especially complicated.

To me, this seems like a herculean effort to create ever more efficient Wall-Es, without trying to address why there was so much for Wall-E to clean up in the first place. Instead of just focusing on the shortage of child psychiatrists, why are we not doing more about the over-abundance of patients? After the session, I asked one of the speakers this very question. Her answer was sobering: she had thought about this issue herself, but when she tried to a submit a paper on the prevention of mental disorders in children, no child psychiatry journal would accept it. She thinks that is just not our mindset, just not what we are trained or paid to do. It reminded me of the old adage by Upton Sinclair, "It is difficult to get a man to understand something, when his salary depends on his not understanding it."

Don't get me wrong, I believe in universal health care. I just don't think that the ACA is going to successfully address the mental health issues of children in this country, just as it won't address the obesity epidemic by making obesity treatment more streamlined. For example, today's NYTimes article that I linked to earlier profiled a California mother who has a child with ADHD and severe behavioral issues. Here's the crucial paragraph:

Some would consider Matthias a textbook candidate for combined treatment. His rages have overwhelmed schools and child care programs for years, and he is already struggling in first grade. He and his mother — a medical technician whose typical workday drawing blood lasts from 7 in the morning until 4 p.m. — share a cramped and clamorous three-bedroom ranch house with her sister and brother-in-law and their spirited children, ages 3 and 6 months. Matthias is having nightmares and bladder-control issues.

I'm not sure that any amount of meds or access to a child psychiatrist would help this child as much as having a less stressful home environment. I don't claim to know what the best solution for our society as a whole would be, but I do think we need to put more effort into investigating what can be done to better support children and families, and not just from a medical/health care system point of view.

I hope that more of us in the child psychiatry field can be a bit more like Wall-E: a bit more curious about the world we find ourselves in and how it became that way, a bit more willing to ponder what can change things for the better. Let's not continue to just put our heads down in order to squeeze ever more efficiency and productivity out of our days.