{"id":40613,"date":"2013-10-08T19:43:53","date_gmt":"2013-10-08T23:43:53","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=40613"},"modified":"2013-10-08T19:49:40","modified_gmt":"2013-10-08T23:49:40","slug":"nowhere-so-far","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/10\/08\/nowhere-so-far\/","title":{"rendered":"nowhere so far…"},"content":{"rendered":"
Remember the DSM-5 Task Force? The Field Trials? The debates about what to call Dr. Biederman’s Bipolar youth once we got over them being Bipolar? The solution was Disruptive Mood Dysregulation Disorder [DMDD]. This time last year, we got to see the DSM-5 Field Trials, and DMDD didn’t fare very well, as it turned out [Questionable<\/em> – with a <\/em>questionable interpretation of Kappa values]: <\/div>\n
\n
DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses and Analytic Approaches<\/font><\/strong><\/u><\/a>
by Darrel A. Regier, William E. Narrow, Diana E. Clarke, Helena C. Kraemer, S. Janet Kuramoto, Emily A. Kuhl, and David J. Kupfer<\/sup>
American Journal of Psychiatry.<\/font><\/strong> 2012 October 30, AJP in Advance<\/font><\/strong><\/div>\n
 <\/div>\n

[modified to fit]<\/sup><\/div>\n<\/blockquote>\n
Dr. Ellen Leibenluft<\/a> is the "Chief of the Section on Bipolar Spectrum Disorders in the Emotion and Development Branch, Mood and Anxiety Program, National Institute of Mental Health, and Clinical Associate Professor of Psychiatry at Georgetown University School of Medicine. Her research focuses on the brain mechanisms involved in bipolar disorder in children and adolescents. In addition, since questions have been raised as to whether children with impairing irritability should be diagnosed with bipolar disorder, Dr. Leibenluft conducts research on this question, including studies on the brain mechanisms mediating severe irritability in children.<\/em>" Now we read this from her group in this month’s AJP: <\/div>\n
\n
Neural Mechanisms of Frustration in Chronically Irritable Children<\/a><\/div>\n
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.<\/div>\n
American Journal of Psychiatry<\/font><\/strong> 2013 170:1186-1194.<\/div>\n

<\/p>\n

Objective<\/font><\/strong><\/u>: 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.<\/div>\n
Method<\/font><\/strong><\/u>: 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.<\/div>\n
Results<\/font><\/strong><\/u>: 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.<\/div>\n
Conclusions<\/font><\/strong><\/u>: 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.<\/div>\n
Received \t\t\t\tJuly \t\t\t 14, 2012; Revised \t\t\t\tJanuary \t\t\t 11, 2013; Accepted \t\t\t\tFebruary \t\t\t 14, 2013.<\/em><\/div>\n
<\/div>\n<\/blockquote>\n
Looking over Dr. Leibenluft’s publications, she seemed to have had one foot in the Bipolar Child Camp at its height, and one foot outside, shuffling back and forth. But gone now is the Bipolar Child, and we have an fMRI study of its replacement, DMDD, under situations of frustration. The article is sort of unique in that it’s a study done on a Disorder before it even existed, but, I suppose being on the DSM-5 Workgroup that created it gives one something of a head start. <\/div>\n

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<\/em>" rather than just recording what a frustrated brain<\/em> looked like – a chicken and egg<\/em> dilemma.<\/p>\n

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: <\/p>\n

\n
Severe Irritability in Youths: Disruptive Mood Dysregulation Disorder and Associated Brain Circuit Changes<\/a><\/div>\n
Editorial<\/font><\/strong><\/div>\n
by  Neal Ryan<\/div>\n
American Journal of Psychiatry<\/font><\/strong> 2013 170:1093-1095.<\/div>\n
[full text on-line<\/a>] <\/div>\n

<\/p>\n

<\/div>\n
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.<\/font><\/strong> 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. <\/div>\n

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. <\/p>\n

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. <\/p>\n

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.<\/div>\n<\/blockquote>\n
I wish I could read this study with the kind of clarity Dr. Ryan describes [in red<\/font><\/strong> above]. I couldn’t find it on multiple readings of the paper. So my first point would be that authors writing about fMRI studies published in general psychiatric journals would do well to have a conference about how to write these studies for the general psychiatric readership. I wondered how much of the effect was from the medications, and couldn’t answer that question. I wondered whether the changes seen were causes or the results of the short fuses of these patients and left confused. So I don’t know if Dr. Ryan’s summary statement is even defensible.<\/div>\n

I’ve seen some of these children and find them particularly confusing. The families are a mess, so the chicken or egg<\/em> question is there too. All of the ones I’ve seen look like they have ADHD [a lot<\/em> 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<\/em> part seems more aimed at<\/em> than aimless<\/em>. In fact, that’s a prominent feature, more defining than the criteria mentioned in the article or the diagnostic layout.<\/font><\/strong> 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 <\/em>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<\/em> gone awry.<\/p>\n

We’re in a rut in psychiatry right now – biased towards the brain<\/em>, biased towards biological treatments<\/em>, biased by being in a hurry to do something<\/em> before we’ve really learned enough to move forward, biased by new technologies<\/em>, biased by our own frustration<\/em>. I pulled that [modified] table up there from the paper because it says to me that we don’t know what we’re doing<\/em> – diagnostically and therapeutically – with our polymeds and polydiagnoses. This is the kind of situation where the NIMH would be well placed to put together a multidisciplinary team who jointly followed a group of these kids longitudinally with enough resources to chase all the leads rather than throwing the technology\/ideology du jour at the problem. Studying them in pieces has gotten us nowhere so far… <\/div>\n","protected":false},"excerpt":{"rendered":"

Remember the DSM-5 Task Force? The Field Trials? The debates about what to call Dr. Biederman’s Bipolar youth once we got over them being Bipolar? The solution was Disruptive Mood Dysregulation Disorder [DMDD]. This time last year, we got to see the DSM-5 Field Trials, and DMDD didn’t fare very well, as it turned out […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-40613","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40613","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=40613"}],"version-history":[{"count":23,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40613\/revisions"}],"predecessor-version":[{"id":40636,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/40613\/revisions\/40636"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=40613"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=40613"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=40613"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}