{"id":65101,"date":"2016-05-02T21:27:54","date_gmt":"2016-05-03T01:27:54","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=65101"},"modified":"2016-05-02T21:33:43","modified_gmt":"2016-05-03T01:33:43","slug":"weary","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/05\/02\/weary\/","title":{"rendered":"weary&#8230;"},"content":{"rendered":"<div align=\"justify\" class=\"small\"><img decoding=\"async\" border=\"0\" align=\"left\" vspace=\"0\" hspace=\"4\" height=\"76\" src=\"http:\/\/1boringoldman.com\/images\/brain-resource.gif\" \/>Five years ago, I ran across an Australian company called <a target=\"_blank\" href=\"https:\/\/www.google.com\/url?sa=t&#038;rct=j&#038;q=&#038;esrc=s&#038;source=web&#038;cd=1&#038;cad=rja&#038;uact=8&#038;ved=0ahUKEwibsu6-jLzMAhVhlYMKHQtPDEIQFggdMAA&#038;url=http%3A%2F%2Fwww.brainresource.com%2F&#038;usg=AFQjCNEiS4CeuFWa1OwGNkjaaheTtrhxhQ&#038;sig2=LzX49Bvx2dNodH-lLBZdFQ\">Brain Resources<\/a>. It appeared to be primarily a Brain Training enterprise, but they were into a lot of other things too. They were financing <a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3036635\/\">iSPOT<\/a>, a clinical trial of <a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/wp-admin\/personalized medicine: BRAINnet\u2026 \">personalized medicine<\/a> trying to predict antidepressant drug choice based on Genetic and\/or other testing. And they were amassing a Database of subjects testing all things neuro [testing, genetics, imaging, etc]. There were two principals: <font color=\"#200020\">Evian Gordon<\/font>, a Brain Training guru type, and <font color=\"#200020\">Leanne Williams<\/font>, second in command, in charge of the database which was to be made publicly available. They had put together an amazing conference in the US about personalized medicine, attended by KOLs from far and wide [<a href=\"http:\/\/1boringoldman.com\/index.php\/7604-2\/\" target=\"_blank\">roster<\/a>][<a href=\"http:\/\/brainnet.net\/media\/video_action.php?playfor=brainnet&#038;iframe=true&#038;width=770&#038;height=480\" target=\"_blank\">video<\/a>] called the <strong><font color=\"#660033\">Mayflower Initiative<\/font><\/strong>. And there were a number of KOLs involved in their iSPOT trial. To be honest, I didn&#8217;t know what to make of it. The personalized medicine meme swept through psychiatry. Besides Brain Resources&#8217; <a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3036635\/\">iSPOT<\/a>, there was <a href=\"http:\/\/1boringoldman.com\/index.php\/2013\/12\/24\/9199613-00-and-counting\/\" target=\"_blank\">EMBARC<\/a>, a similar trial funded by the NIMH with Madhukar Trivedi as P.I. Nemeroff gave talks about it. <a href=\"https:\/\/www.google.com\/url?sa=t&#038;rct=j&#038;q=&#038;esrc=s&#038;source=web&#038;cd=1&#038;cad=rja&#038;uact=8&#038;ved=0ahUKEwih44L3lLzMAhVKkIMKHeqLASkQFggiMAA&#038;url=http%3A%2F%2Fwww.nimh.nih.gov%2Fabout%2Fdirector%2F2011%2Fimproving-diagnosis-through-precision-medicine.shtml&#038;usg=AFQjCNENylHtVm6bJqw8o_GDWoiSO6d-tQ&#038;sig2=5XkpvsRSsaEABcWQTfFVEg\" target=\"_blank\">Insel<\/a> blogged about it. <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25815420\" target=\"_blank\">Papers<\/a> were published along the way.    <\/div>\n<p align=\"justify\" class=\"small\"><img decoding=\"async\" border=\"0\" align=\"left\" hspace=\"4\" height=\"76\" src=\"http:\/\/1boringoldman.com\/images\/nimh-logo.gif\" \/>Meanwhile, right around the same time, Tom Insel&#8217;s NIMH introduced its <font color=\"#200020\">Research Domain Criteria <\/font>[<font color=\"#200020\">RDoC<\/font>] [<a href=\"https:\/\/www.nimh.nih.gov\/news\/science-news\/2010\/genes-and-circuitry-not-just-clinical-observation-to-guide-classification-for-research.shtml\" target=\"_blank\">Genes and Circuitry, Not Just Clinical Observation, to Guide Classification for Research<\/a> January 2010]. Born from the frustration of the poor specificity of psychoactive drugs for clinical diagnosis, the <font color=\"#200020\">RDoC<\/font> proposed to search for other parameters that might define syndromes that more accurately map to drug response. But while <font color=\"#200020\">personalized medicine<\/font> and the <font color=\"#200020\">RDoC<\/font> may sound like different things, operationally, they&#8217;re the same &#8211; broad surveys of objective parameters [genomic, imaging, clinimetrics, etc] analyzed looking for clusters or correlations not apparent in the traditional clinical categories [using <em><font color=\"#200020\">big data<\/font><\/em> statistical techniques].   <\/p>\n<div align=\"justify\" class=\"small\">But that&#8217;s not all folks! When I first wrote about this five years ago, <em><font color=\"#200020\">Leanne Williams<\/font><\/em> was the curator of the data being collected by the <font color=\"#200020\">Brain Resources Company in Australia<\/font>. Now <em><font color=\"#200020\">Leanne Williams<\/font><\/em> [one and the same] is the Director of the <font color=\"#200020\">Panlab at Stanford and the VA Palo Alto MIRECC<\/font> and the curator of the data being collected by the NIMH as PI of a big NIMH grant &#8211; part of their RDoC Initiative.    <\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/www.thelancet.com\/journals\/lanpsy\/article\/PIIS2215-0366%2815%2900579-9\/abstract\">Precision psychiatry: a neural circuit taxonomy for depression and anxiety<\/a><\/div>\n<div align=\"center\" class=\"middle\">by Leanne M Williams<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">Lancet Psychiatry.<\/font><\/strong> 2016, Published Online April 14, 2016<\/div>\n<p>    <\/p>\n<div align=\"justify\">Although there have been tremendous advances in the understanding of human dysfunctions in the brain circuitry for self-reflection, emotion, and cognitive control, a brain-based taxonomy for mental disease is still lacking. As a result, these advances have not been translated into actionable clinical tools, and the language of brain circuits has not been incorporated into training programmes. To address this gap, I present this synthesis of published work, with a focus on functional imaging of circuit dysfunctions across the spectrum of mood and anxiety disorders. This synthesis provides the foundation for a taxonomy of putative types of dysfunction, which cuts across traditional diagnostic boundaries for depression and anxiety and includes instead distinct types of neural circuit dysfunction that together refl ect the heterogeneity of depression and anxiety. This taxonomy is suited to specifying symptoms in terms of underlying neural dysfunction at the individual level and is intended as the foundation for building mechanistic research and ultimately guiding clinical practice.<\/div>\n<\/blockquote>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/stanmed.stanford.edu\/2016winter\/brain-waves.html#\">How neuroscience could determine your mental health treatment<\/a><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#200020\">Brain waves<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\">By Tracie White<\/div>\n<div align=\"center\" class=\"middle\">Stanford Medicine, Winter 2016<\/div>\n<p>    <\/p>\n<div align=\"justify\"><em>&#8230; a fluff-piece in the Stanford Medicine Magazine about Dr. Leanne Williams&#8230;<\/em><\/div>\n<\/blockquote>\n<blockquote>\n<div align=\"center\" class=\"big\"><a target=\"_blank\" href=\"http:\/\/bmcpsychiatry.biomedcentral.com\/articles\/10.1186\/s12888-016-0771-3\">Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression [&ldquo;RAD&rdquo;] project<\/a><\/div>\n<div align=\"center\" class=\"middle\">by Leanne M. Williams, Andrea N. Goldstein-Piekarski, Nowreen Chowdhry, Katherine A. Grisanzio, Nancy A. Haug, Zoe Samara, Amit Etkin, Ruth O&rsquo;Hara, Alan F. Schatzberg, Trisha Suppes, and Jerome Yesavage<\/div>\n<div align=\"center\" class=\"middle\"><strong><font color=\"#200020\">BMC Psychiatry<\/font><\/strong>. DOI: 10.1186\/s12888-016-0771-3. Published: 15 March 2016<\/div>\n<div align=\"center\" class=\"middle\">[<a target=\"_blank\" href=\"http:\/\/bmcpsychiatry.biomedcentral.com\/articles\/10.1186\/s12888-016-0771-3\">full text online<\/a>]<\/div>\n<p>    <\/p>\n<div align=\"justify\"><strong><font color=\"#200020\">Background<\/font><\/strong>: Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria [RDoC] initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression [&ldquo;RAD&rdquo;] project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are [a] to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, [b] to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and [c] to assess the stability of brain-symptom-behavior-function relationships over time.<\/div>\n<div align=\"justify\"><strong><font color=\"#200020\">Methods and design<\/font><\/strong>:  Here we present the protocol for the &ldquo;RAD&rdquo; project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who &ldquo;walk through the door&rdquo; of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain&ndash;based subgroups over time and to assess whether these subgroups predict real&ndash;world functional capacity over time. First enrollment was August 2013, and is ongoing.<\/div>\n<div align=\"justify\"><strong><font color=\"#200020\">Discussion<\/font><\/strong>:  This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward.<\/div>\n<div align=\"justify\"><strong><font color=\"#200020\">Trial registration<\/font><\/strong>: ClinicalTrials.gov Identifier: <a target=\"_blank\" href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02220309\">NCT02220309.<\/a><\/div>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">I don&#8217;t know much about <strong><font color=\"#200020\">neural circuits<\/font><\/strong>. Let me rephrase that &#8211; I don&#8217;t know anything about <strong><font color=\"#200020\">neural circuits<\/font><\/strong>. I first heard the term here&#8230;<\/div>\n<blockquote>\n<div align=\"center\" class=\"big\"><a href=\"http:\/\/www.bmj.com\/content\/343\/bmj.d5581.extract?ct\" target=\"_blank\">Brain circuitry model for mental illness will transform management, NIH mental health director says<\/a><\/div>\n<div align=\"center\" class=\"big\"><strong><font color=\"#0066ff\">British Medical Journal<\/font><\/strong><\/div>\n<div align=\"center\" class=\"middle\">by Caroline White<\/div>\n<div align=\"center\" class=\"middle\">1 September 2011<\/div>\n<p align=\"justify\">The   field of mental health is on the cusp of a revolution, which is set to   transform the diagnosis and treatment of mental illness and reverse  the  lack of major progress made in curbing associated ill health and  death  over the past 100 years, the director of the US National  Institute of  Mental Health, has claimed. &ldquo;We are at an extraordinary  moment when the  entire scientific foundation for mental health is  shifting, with the  20th century discipline of psychiatry becoming the  21st century  discipline of clinical neuroscience,&rdquo; Thomas Insel said  before a meeting  on the challenges facing mental health research at the  Royal Society in  London on 31 August&#8230;<\/p>\n<p align=\"justify\"><em><strong><font color=\"#990000\">The  seismic  shift had been driven by what he described as three  &ldquo;revolutionary  changes&rdquo; in thinking, the first of which was that mental  illness was  increasingly being recognised as a disorder of brain  circuitry, rather  than as a chemical imbalance, thanks to neuroimaging  techniques and the  discovery of some key biomarkers.<\/font><\/strong><\/em> Secondly, mental  ill health was now  recognised as a developmental disorder for which  early intervention was  vital, said Professor Insel, highlighting US  research showing that 50%  of study participants had reported the onset  of mental health problems  by the age of 14, and 75% by the age of 24.  &ldquo;We are still stuck with  getting to the problem very late. The future  will be about understanding  the trajectory of illness so that we can  identify the first signs  before it develops into psychosis,&rdquo; he said&#8230;<\/p>\n<div align=\"justify\">[see also <a href=\"http:\/\/www.nimh.nih.gov\/about\/director\/2011\/mental-illness-defined-as-disruption-in-neural-circuits.shtml\" target=\"_blank\">Director&rsquo;s Blog: Mental Illness Defined as Disruption in Neural Circuits<\/a>, <a href=\"http:\/\/www.psychnews.org\/update\/update_AM_14_1_a.html\" target=\"_blank\">Insel Outlines the Psychiatry of the Future Treating Disorders of Neural Circuitry<\/a>]<\/div>\n<\/blockquote>\n<div align=\"justify\" class=\"small\">&#8230; so the main person talking about <strong><font color=\"#200020\">neural circuits <\/font><\/strong>has been Dr. Insel up until now. I can&#8217;t even tell if this is coming from his standard neuroscience cheerleading or some solid thread in neuroscience research. Likewise, I don&#8217;t know how all this boundary blurring connectedness between Evian Gordon&#8217;s <em><font color=\"#200020\">Brain Resources<\/font><\/em> and Insel&#8217;s <em><font color=\"#200020\">NIMH<\/font><\/em> works, or how <em><font color=\"#200020\">Leanne Williams<\/font><\/em> fits into the story, or how Dr. Insel&#8217;s gloomy quip about the indadequate <em><font color=\"#200020\">analytic firepower<\/font><\/em> mentioned in <a href=\"http:\/\/1boringoldman.com\/index.php\/2016\/04\/30\/the-chemistry-of-paint\/\" target=\"_blank\">the chemistry of paint&hellip;<\/a> relates. Reading these papers, clearly intended to be an enthusiastic launching pad for this study of <strong><font color=\"#200020\">neural circuits<\/font><\/strong>, I&#8217;ll admit to feeling something sort of like <em><font color=\"#200020\">weary<\/font><\/em> &#8211; like<em><font color=\"#200020\"> &quot;here we go again [sigh]&quot;<\/font><\/em>. I guess we&#8217;ll see&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Five years ago, I ran across an Australian company called Brain Resources. It appeared to be primarily a Brain Training enterprise, but they were into a lot of other things too. They were financing iSPOT, a clinical trial of personalized medicine trying to predict antidepressant drug choice based on Genetic and\/or other testing. And they [&hellip;]<\/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":[5],"tags":[],"class_list":["post-65101","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65101","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=65101"}],"version-history":[{"count":33,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65101\/revisions"}],"predecessor-version":[{"id":65134,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65101\/revisions\/65134"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=65101"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=65101"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=65101"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}