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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAlthough a variety of treatments for major depression are available, less than 40% of patients achieve remission with their first treatment [Rush AJ et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006], and approximately 10% becomes treatment-resistant over time. New treatments are needed for patients who remain depressed despite having tried all available therapies. This article discusses the use of deep brain stimulation as a treatment for patients with chronic, treatment-resistant depression who have failed all other therapies.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eneuroimaging\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eextrapyramidal \u0026amp; movement disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emood disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2006150082\u0022 data-figure-caption=\u0022\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure1\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure1\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10920\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EMajor depression is the most common of all psychiatric disorders [Wang PS. \u003Cem\u003EJAMA\u003C\/em\u003E 2003] and the leading cause of disability in North America among adults under 50 years of age [World Health Organization 2001]. Although a variety of treatments are available, less than 40% of patients achieve remission with their first treatment [Rush AJ et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 2006], and approximately 10% becomes treatment-resistant over time. Although electroconvulsive therapy (ECT) is effective for many patients, those who have failed to respond to 4 previous antidepressant treatments are likely to relapse (CORE). New treatments are needed for patients who remain depressed despite having tried all available therapies.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EHelen Mayberg, MD, Emory University, Atlanta, GA, has been investigating the use of deep brain stimulation (DBS) as a treatment for patients with chronic, treatment-resistant depression who have failed all other therapies. According to Dr. Mayberg, \u201cIt is now clear that depression cannot be viewed as simply a chemical \u201cshortage\u201d but rather as a more complex disorder of dysfunctional brain circuits.\u201d The emerging evidence, made possible in large part by advances in imaging technology, indicates that depression is a \u201csystems-level disorder affecting integrated pathways linking select cortical, subcortical, and limbic sites and their related neurotransmitter and molecular mediators\u201d [Mayberg HS et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EAlthough there are several circuits that might be targeted to produce clinical benefit in patients with treatment-resistant depression, Dr. Mayberg and her colleagues are particularly interested in the subgenual cingulate region of the brain (Cg25). Studies have indicated that Cg25 may play a role in modulating negative mood states [Mayberg HS et al. \u003Cem\u003EAm J Psychiatry\u003C\/em\u003E 1999; Seminowicz DA et al. \u003Cem\u003ENeuroimage\u003C\/em\u003E 2004], and a decrease in Cg25 activity has been shown in response to select SSRIs, ECT, repetitive transcranial magnetic stimulation (rTMS), and ablation [Mayberg HS et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2005]. It also has been suggested that certain Cg25 connections may be involved in the sleep, libido, appetite, and neuroendocrine disturbances that are associated with depression [Mayberg HS et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2005], as well as have an effect on other core behaviors that are affected by depression (eg, learning, memory, motivation, and reward).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe use of chronic high-frequency DBS has been shown to be effective in the treatment of Parkinson disease. Using that knowledge and evidence from worldwide studies that have shown that DBS produced local and remote changes in neural activity when applied to the basal ganglia, Dr. Mayberg and her colleagues continue to study the effect of DBS that is targeted to the Cg25 white matter of chronically depressed patients who do not respond to standard therapies.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EDBS is accomplished using three-dimensional magnetic resonance imaging to guide the bilateral placement of very small wires deep into the brain. Patients are awake during this part of the procedure and have their skull secured in a special frame that allows very precise placement. The wires contain 4 contacts that span the areas to be stimulated. Once inserted, the contacts are tested to ensure that they are properly placed and to determine the appropriate level of stimulation. Following this, the patient is put to sleep, and the other end of the wire is connected to a small cable under the skin in the neck and then to a small battery pack. Ongoing stimulation is accomplished using a magnet and a small external control box (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Deep Brain Stimulation.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2006150082\u0022 data-figure-caption=\u0022Deep Brain Stimulation.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10923\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EDeep Brain Stimulation.\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EPhoto courtesy of Medtronic.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EIn 2005, Dr. Mayberg and colleagues published the preliminary results of a pilot study of DBS in 6 patients with chronic, treatment-resistant depression [Mayberg HS et al. \u003Cem\u003ENeuron\u003C\/em\u003E 2005]. In this study, patients showed progressive improvement over several weeks, and by 3 months, the investigators were able to distinguish between those patients who would go on to do well and those who would not. Four of the 6 patients achieved a good clinical result at 6 months (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 2\u003C\/a\u003E). Follow-up continues on all patients, and the initial 4 responders continue to do well more than 4 years out with continuous DBS. As of 2008, 20 patients have received DBS implants as part of the original pilot study. Approximately 50 patients worldwide have been implanted in this same brain target, and placebo-controlled studies are now underway. Final results of the original 20-patient pilot project are now in press. Although these studies clearly offer hope to patients who have not responded to other treatments, Dr. Mayberg cautioned that \u201cbehavioral rehabilitation is still needed for patients after DBS.\u201d\u003C\/p\u003E\n         \u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u00226-Month Results.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2006150082\u0022 data-figure-caption=\u00226-Month Results.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/8\/3\/7\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/10926\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003E6-Month Results.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EIn closing Dr. Mayberg said, \u201cThe combination of deep brain stimulation and advanced imaging capabilities have given us new insights into the pathogenesis of depression that are laying the foundation for a whole new approach to the treatment of psychiatric disorders.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2008 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/8\/3\/7.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzmdh2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmdh2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}