DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses and Analytic Approaches
by Darrel A. Regier, William E. Narrow, Diana E. Clarke, Helena C. Kraemer, S. Janet Kuramoto, Emily A. Kuhl, and David J. Kupfer
American Journal of Psychiatry. 2012 October 30, AJP in Advance
[modified to fit]
by Christen M. Deveney, Ph.D.; Megan E. Connolly, B.A.; Catherine T. Haring, B.A.; Brian L. Bones, B.A.; Richard C. Reynolds, M.S.; Pilyoung Kim, Ph.D.; Daniel S. Pine, M.D.; and Ellen Leibenluft, M.D.American Journal of Psychiatry 2013 170:1186-1194.
Objective: Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation.Method: The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children [operationalized using criteria for severe mood dysregulation] and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions.Results: Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group [i.e., between-group effect] and to the severe mood dysregulation group’s responses on positive feedback trials [i.e., within-group effect]. In contrast, neural response to positive feedback during the frustration condition did not differ between groups.Conclusions: In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.Received July 14, 2012; Revised January 11, 2013; Accepted February 14, 2013.
The problem of extremely irritable temper tantrum children is very real. While many [like me for example] think that Dr. Biederman’s labeling these kids as Bipolar was a mistake and an excuse to use antipsychotics for behavior control, that’s not to say that these kids don’t exist and need to be studied. I’m not sure renaming them as DMDD adds much and the Field Trials certainly don’t give us much confidence that they even represent a distinct category. Reading this article didn’t give me any clarity either. The DMDD kids were easier to frustrate than normals and there were changes reported in the fMRIs during frustration. But I couldn’t see how they could say that they were looking at the "Neural Mechanisms of Frustration" rather than just recording what a frustrated brain looked like – a chicken and egg dilemma.
I’m interested in the fMRI technique as a way of seeing the brain in action, but I always leave the studies confused. I hope they are more convincing up close and personal than they are in the reading. I found these results impossible to follow from the narrative report. They said the findings held in the unmedicated kids and referred to a Supplementary Table, but the Table didn’t match the narrative description. So I often feel I’m being asked to take somebody’s word for things in these fMRI reports [and that’s a reach in today’s psychiatric climate]. Dr. Neal Ryan [Principle Investigator on Paxil Study 329 back in 2001] wrote the accompanying editorial. After describing the findings, he concluded:
Editorialby Neal RyanAmerican Journal of Psychiatry 2013 170:1093-1095.
In summary, youths with severe mood dysregulation exhibited markedly decreased activation of neural regions associated with spatial attention, reward processing, and emotional salience after negative feedback [frustrating] trials. In contrast to expectations, this study did not find group differences in prefrontal regions, and the authors theorize that because of the small sample size, this could simply be a type II statistical error. As the authors point out, this constellation of findings may be related to the chronic irritability in disruptive mood dysregulation disorder, the required hyperarousal in severe mood dysregulation, the irritability across diagnostic groups, or, conceivably, the highly comorbid attention deficit hyperactivity disorder seen in the sample.What is particularly interesting and important about this study and approach? First, of course, the authors have picked a problem associated with high morbidity and current diagnostic uncertainty, a very important clinical area. And they have found a pattern of brain responses that appears different, and this finding will allow exploration of this particular pattern in irritability in a wide range of other psychiatric disorders.
In addition, this study may serve as a great example of how to make progress thinking about the relationship between specific symptoms, rather than current categorical diagnoses, and brain function in youths. The Research Domain Criteria initiative proposes starting from neural systems responsible for implementing the primary behavioral functions of the brain and considering psychopathology in terms of disruptions of these systems. It emphasizes dimensional approaches rather than categorical approaches and developing measures that work across full dimensional ranges, not just normal or pathological ranges. Broad sampling frames including subjects who do not fall within traditional diagnostic borders are explicitly included.
The argument that we can further progress by starting from neural underpinnings and working toward psychiatric symptoms and syndromes is compelling. However, there are many different stages of development, so there are important areas where our knowledge of brain systems during development is sketchier than our understanding of the adult rat, monkey, or human. In addition, human developmental understanding of neural systems is constrained because some informative approaches [e.g., positron emission tomography] are not usable in normal youths, and there are very few brains of children and adolescents in available brain banks. So starting from important symptoms [e.g., irritability] and working toward neural systems while incorporating the other Research Domain Criteria approaches [e.g., full range of symptom levels from normal to impaired, wide range of diagnoses, multilevel assessments, and dimensional rather than categorical measures] may be an important strategy in future studies of irritability and other symptoms that span multiple disorders.
I’ve seen some of these children and find them particularly confusing. The families are a mess, so the chicken or egg question is there too. All of the ones I’ve seen look like they have ADHD [a lot of ADHD] but I’m not convinced it’s a comorbidity, but rather part of the package. They’re often on a medley of medications as in this cohort. And in person, they seem interpersonally disconnected to me. The disruptive part seems more aimed at than aimless. In fact, that’s a prominent feature, more defining than the criteria mentioned in the article or the diagnostic layout. I looked at this study not to be critical, but with curiosity. In the past, I read Dr. Biederman’s articles suggesting this was some kind of bipolar equivalent the same way. But I have to say that I didn’t read anything here that felt any more on target than he was. The hypothesis that this is a brain driven frustration intolerance or irritability remains a speculation. And I’m not sure that Dr. Ryan’s pulling it into the RDoC orbit is justified by these findings – some kind of across the board fMRI signal of irritability circuits gone awry.
How these fMRI studies reveal “neural circuitry or systems” deficits is bewildering. At least to me. What defines a “circuit” or “system” at a neuroanatomical level? Where does the “circuit” (not to mention the “system”) begin or end? Moreover, this study compares irritable kids to “normals.” I wonder if they included comparison samples of depressed, or inattentive, or behavior disordered, or Learning Disordered, or “whatever” kids, would you obtain the same findings? I mean are these fMRI results specific to the “mood dis- regulation irritable” kids, or would they be seen in any child sample comprised of “dis-eased” subjects?
Tom,
DMDD isn’t even a “thing” yet, if ever. “Neural circuits” are a hypothesis at best. It’s as if they are trying to hit home runs every time instead of trying to get on base. What bothered me was this is the NIMH intramural section, the ones that are supposed to provide an overview. 15/19 with ADHD? 16/19 with ODD? On Stimulants, Li, Antidepressants, Atypicals, and Anticonvulsants? Mush…
Actually there’s a good reason why these studies have gone nowhere.
A functional test only allows one to see if the brain is operating properly when compared to healthy controls, it can’t tell you what the brain is actually doing. Nothing like that yet exists.
We don’t know what the brain is actually doing, and thats why we need a database of healthy controls to compare our results to.
Brain regions that are involved in “spatial attention, reward processing, and emotional salience” are behavioral or cognitive neuroscience conjecture. They aren’t used in clinical practice in neurology, neurolgy uses a different map that is far more restrictive.
Until we can model a human brain in a computer, the tasks performed by any part of the brain are soley conjecture. There is literally no way to determine the actual tasks being performed. While some areas a critical for certain things, and damage to them affects that process, that doesn’t mean it’s what they specifically do, or soley what they do.
The National Insitute of Neurological Disorders and Stroke has a page about the fuctions of different regions of the brain.
http://www.ninds.nih.gov/disorders/brain_basics/know_your_brain.htm
Under the “The Geography of Thought” are the differen’t functions of brain regions. What we can see is that every part is limited only to the basic objective clinical function it is critical for.
Beyond that, it’s all conjecture.
The only engineering approach to determine the exact function of more general areas is create a means to map out all the neruons and synapatic connections as they are running. Then take that data and model them out on a computer, then store the simulated activity (of neurons/connections) in a database. The database can then be analyized afterward to determine what was actually happening.
What the NIMH wants to do is not real. The $100 million taxpayer money should have gone striaght to engineers to build a functional test to map connections, not researchers and scammers rambling about fake sythetic DNA (pretending to perfrom the function of a database in a computer), none of that was ever plausable or real. It is pure unadulterated bullshit, by scammers.
We already have 3 functional tests in mainstream medicine. Some existing functional tests could be further developed to map out the connections themselves – allowing us to continue past that point. The NIMH wants ‘invent’ something that already exists! So they spend the money on psudo-research instead of engineering. That’s how absurd all this is…
Just as all neuroimaging studies for mental illness are 🙁
I have heard many stories about how easily beurocrats are tricked into funding things, using fake brightly lit mockups and big words. They don’t understand how engineering or science works. It’s all very true.
Mickey, I think you hit the nail on the head with your last paragraph.
I’ve long admired Dr. Leibenluft’s work, since she was one of the leaders behind discrediting the whole Biederman/Wozniak conception of bipolar children. Her group was instrumental in conducting longitudinal studies that showed children with chronic irritability were more likely to be diagnosed with depression and did not have an elevated risk of developing mania.
However, instead of examining these children in a holistic way, it seems that her research (like much of NIMH research) focuses on “biological mechanisms,” examining the brains of these children for dysfunction without considering the likely influence of family dynamics and parent-child interactions. It’s very depressing.
On a perhaps tangentially related note, Neuroskeptic had a post today about a study showing that behaviors like hyperactivity and conduct disorder are heritable, but not genetic, if I read it right. Really puts into question the whole endeavor of examining behavior by focusing on biology…
The absence of evidence is not evidence of absence.
The syndromal- categorical- approach to diagnosis is most clearly supported by remission-either “natural” or induced. For instance Kraepelin observed that within his welter of syphilitics,brain damaged,pellagra,beri-beri,senile,trisomy 21’s,dementia precox,etc some just got better-restored to normal-
Those folks had a remitting dysfunction with multiple manifestations–that enabled Kraepelin to distinguish, by baseline characteristics, dementia praecox from manic – depression.
The same logic leads by pharmacologic dissection to panic disorder,atypical depression etc.
If these syndromes are due to a particular brain function becoming impaired–there is no necessity for common genotypes or developmental traumas etc since a function can be impaired in innumerable ways.
Insisting on a “dimensional ” approach as all-embracing simply ignores important history. Maybe sometimes–but not as a dictum.
“Brain-driven frustration” is an oxymoron. Frustration always needs an external trigger.
Sorry for the length. I don’t have time to rewrite this and make it pithy, and I’m angry.
So, using a fledgling and naive technique of imaging, with the “logic” of an unsupported hypothesis, to detect a condition with no scientifically based taxonomy, in the brain of a human in a demographic whose neurological development and reaction to drugs and the drug’s effect on development is least understand; in order to justify and rationalize the use of drugs before knowing a child, the child’s life situation, and the child’s relationship within the family is so much more discerning and critical than labeling the child with bipolar disorder and medicating that child accordingly that I’m completely flummoxed by this.
Even with good enough parents, if, for example the child has a temperament that requires order, quiet, and routine; yet has parents who are incapable of understanding that, much less providing it— and no other adult in the child’s life recognizes that and validates it— then the child is going to be living in a state of insecurity and unrest with a feeling of being out of place or contrary and is going to have a difficult time getting his/her needs met. This is especially true when the child’s parents are unreliable, thoughtless, lacking an understanding about how (different) children learn (differently) or what is appropriate for their child at the stage of development,* and rarely says what they mean and mean what they say, so that they make the words their child is learning meaningless, then they are going to make trust difficult— that is a recipe for meltdowns.
There are parents who could make the angels snap and pound their heads against a wall.
This and the fact that psychiatrists and others who prescribe aren’t required to do what they can to rule out physical illnesses— and are unlikely to remove a psychiatric diagnosis after a physical cause of psychiatric symptoms has been found (it’s conveniently “comorbid”) is what makes me feel like tearing it all down with my fingernails sometimes— futility is a lousy and frustrating feeling.
At this point, there is no way that the mental health field can even account for all the damage it has done, much less compensate for it. Because I don’t want to throw the baby out with the bathwater, I have to work hard sometimes not to hate this industry. On my behalf, I’m disregarding it’s opinion of me and refusing to fill out it’s silly little forms, but children can’t do that.
When I see or hear of children being abused and neglected I want Jesus to come back and whoop butt. Now they are being experimented on with bad science. If psychiatrists can’t advocate for the most helpless among us, then what good are they? Sure, there are some like you, Mickey, and I can’t express how much your understanding and words mean to me, but you’re outnumbered. This makes me much more angry than my bad experiences with psychiatry. As an adult who often feels that “all children are mine” these labels, the neglect, the drugging, and abuse of children makes me feel helpless and furious.
Being a child can be so lonely, confusing, and frustrating. Do these psychiatrists who are focused on drugging children remember their own childhood, who they were, what they thought? .
* which is an average or mean that is not appropriate that should not be applied to individual children
shriek