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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.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\u003EThe medical advances of the last 30 years have been nothing less than astonishing; since 1970, there has been a 52% decrease in mortality from heart disease [Jemal A et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2005], and for the past decade, annual cancer deaths in the United States have fallen [Espy DK et al. \u003Cem\u003ECancer\u003C\/em\u003E 2007]. Thomas Insel, MD, Director, National Institute of Mental Health (NIMH), would like to extend the scope of these accomplishments to psychiatry.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Esubstance-related disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emood disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eschizophrenia\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneurodevelopmental disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EThe medical advances of the last 30 years have been nothing less than astonishing; since 1970, there has been a 52% decrease in mortality from heart disease [Jemal A et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2005], and for the past decade, annual cancer deaths in the US have fallen [Espy DK et al. \u003Cem\u003ECancer\u003C\/em\u003E 2007]. Thomas Insel, MD, Director, National Institute of Mental Health (NIMH), would like to extend the scope of these accomplishments to psychiatry.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EConsider the practice of medicine at large. In many ways, life is not as perilous as it once was; acute diseases, such as smallpox, are in sharp decline, and diseases that once were uncontrolled are now chronic, such as diabetes and hypertension. There is also movement toward personalized medicine. \u201cWe\u0027re moving from an era of \u2018average\u2019 medicine to a different kind of science\u2014a way to tailor treatments to individual patients,\u201d said Dr. Insel. This new way of thinking is well underway in oncology. Genetics is also having a continuing impact. The concept of Mendelian disease, in which pathology hinges on single, discrete mutations, such as in cystic fibrosis, is giving way to the reality that there often is a broad interplay of genes and regulatory pathways that are involved in a resulting pathologic phenotype. Again, cancer research largely has pointed the way. Dr. Insel proposes to apply these lessons to mental illness. \u201cIn our field, diagnosis is by observation\u2014detection is late, and the ability to predict outcome poor. We know little about the causes of the most severe disorders,\u201d he continued. Treatment largely is empirical, and no one is talking about cures. \u201cI don\u0027t believe we have even the beginnings of research for a vaccine for schizophrenia or autism,\u201d said Dr. Insel. \u201cThe bottom line is that neither prevalence nor mortality has decreased for any mental illness.\u201d\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EIt\u0027s not as though research is lacking because psychiatric illnesses are rare. Mental disorders, including alcohol and drug addiction, account for half of the total disease burden in industrialized nations (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). In the US, it\u0027s estimated that 6% of the population has a disabling mental illness [Kessler RC et al. \u003Cem\u003EArch Gen Psychiatry\u003C\/em\u003E 2005], with over 28,000 related suicides (the annual rate for homicide is approximately 18,000 people per year; Conwell Y and Brent D. \u003Cem\u003EInternational Psychogeriatrics\u003C\/em\u003E 1995; CDC Web-based Inquiry Statistics Query and Reporting System. \u003Ca href=\u0022http:\/\/www.cdc.gov.ncipc\/wisqars\/default.htm\u0022\u003Ewww.cdc.gov.ncipc\/wisqars\/default.htm\u003C\/a\u003E). Mental illness also precipitates physical illness, resulting in an average age at time of death of 56 years in this population [Colton CW, Manderscheid RW. \u003Cem\u003EPreventing Chronic Disease: Public Health Research, Practice and Policy\u003C\/em\u003E 2006]. The need is clear. In order to enjoin the progress that has been seen in other disease states, Dr. Insel commends the broad adoption of 3 concepts that are now evolving in the field of psychiatry:\u003C\/p\u003E\n         \u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-5\u0022\u003EMental disorders are brain disorders\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-6\u0022\u003EMental disorders are developmental disorders\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n               \u003Cp id=\u0022p-7\u0022\u003EMental disorders result from complex genetic risk, plus experiential factors\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ul\u003E\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\/9\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Burden of Disease (DALYs).\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1714054590\u0022 data-figure-caption=\u0022Burden of Disease (DALYs).\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\/9\/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\/9\/F1.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\/9\/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\/10928\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 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EBurden of Disease (DALYs).\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EBrain disorders\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003E\u201cNeurologists deal with dead cells\u2014observable gross lesions. Psychiatrists deal with circuit problems,\u201d said Dr. Insel. Only recently has the technology been available to image what is happening in brains of the mentally ill. Shaw and colleagues at the NIMH performed a brain imaging study of 223 children, aged 7\u201312 years, with diagnosed ADHD and 233 controls. Results showed a temporal deficit in cortical development in the ADHD children \u003Cem\u003E[Proc Natl Acad Sci\u003C\/em\u003E 2007]. \u201cThese kids are about 3 years behind, developmentally,\u201d said Insel. \u201cADHD can now be seen as a disease of cortical maturation\u2014a brain disorder with cognitive and behavior manifestations.\u201d This perspective immediately suggests a direction for treatment: Are cells not dividing? Do current medications have an impact on the maturation process? Already, there are new things to consider.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EDepression also is yielding its physiologic secrets. Structural scans are elucidating dysfunction within the subgenual cingulate, also called Cg25, a region that is both reduced in volume and increased in activity in people with depression, some of which seems to be due to a reduction in glia \u003Cem\u003E[Nature\u003C\/em\u003E 1997]. Data also show that when patients are treated for depression\u2014irrespective of the methodology, pharmacotherapy or cognitive behavioral therapy (and even placebo)\u2014there is a reduction in the metabolic activity in this region. \u201cThis is not the \u2018home\u2019 of depression,\u201d Dr. Insel cautions. \u201cIt\u0027s a gateway. The important thing to remember is that this is a circuit problem. There are many ways into this circuit, suggesting new targets to treat depression.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDevelopmental Disorders\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EThe concept of mental disorders as developmental disorders is lost because the diagnosis tends to occur many years after the onset of symptoms. A recent study of adolescents looked at the epsilon4 allele of the ApoE gene\u2014a risk factor for Alzheimer disease\u2014and found that children who carried the risk allele already had a loss of cortical volume in the area that typically shows pathology at Alzheimer disease onset [Shaw P et al. \u003Cem\u003ELancet Neurol\u003C\/em\u003E 2007]. These children have no cognitive deficit, but these imaging findings suggest that a pathological process already is underway. Dr. Insel suggests a similar approach in schizophrenia by imaging those who exhibit the \u2018prodrome,\u2019 early characteristics of schizophrenia that precede psychosis [\u003Cem\u003EArch Gen Psych\u003C\/em\u003E 2008]. \u201cFor the last 20 years, we\u0027ve been looking at schizophrenia as a disease that is defined by psychosis. I want to suggest to you that it\u0027s in this prodromal phase or even before the onset of the prodrome where we might have the best options for interventions with the greatest public health impact.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EGenetic Risk\u003C\/h2\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThe human genome contains millions of variations, large and small, which in aggregate may produce the phenotypes that are seen as psychopathology. Some of the same regions of variability appear to contribute to multiple, seemingly unrelated conditions; eg, Duchenne muscular dystrophy appears to involve some of the same genetic risk factors as common forms of heart disease, Crohn disease is related to certain cancers, and celiac disease shares genes with diabetes. \u201cThese are entirely new insights into pathophysiology,\u201d said Dr. Insel. There are no reliable associations for mental disorders as yet, but the work is underway. \u201cI suspect that we\u0027re going to have a very different impression of what many of these disorders are.\u201d Yet, the value to be gained is not to provide a code for diagnosis, but a key to determining risk for a given patient, a pathway for discovering mechanisms of disease, and the possibility of developing preemptive treatments.\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\/9.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?nzmdm1\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?nzmdm1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}