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      Classification of Different Therapeutic Responses of Major Depressive Disorder with Multivariate Pattern Analysis Method Based on Structural MR Scans

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          Abstract

          Background

          Previous studies have found numerous brain changes in patients with major depressive disorder (MDD), but no neurological biomarker has been developed to diagnose depression or to predict responses to antidepressants. In the present study, we used multivariate pattern analysis (MVPA) to classify MDD patients with different therapeutic responses and healthy controls and to explore the diagnostic and prognostic value of structural neuroimaging data of MDD.

          Methodology/Principal Findings

          Eighteen patients with treatment-resistant depression (TRD), 17 patients with treatment-sensitive depression (TSD) and 17 matched healthy controls were scanned using structural MRI. Voxel-based morphometry, together with a modified MVPA technique which combined searchlight algorithm and principal component analysis (PCA), was used to classify the subjects with TRD, those with TSD and healthy controls. The results revealed that both gray matter (GM) and white matter (WM) of frontal, temporal, parietal and occipital brain regions as well as cerebellum structures had a high classification power in patients with MDD. The accuracy of the GM and WM that correctly discriminated TRD patients from TSD patients was both 82.9%. Meanwhile, the accuracy of the GM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 82.4%, respectively; and the WM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 91.2%, respectively.

          Conclusions/Significance

          These results suggest that structural MRI with MVPA might be a useful and reliable method to study the neuroanatomical changes to differentiate patients with MDD from healthy controls and patients with TRD from those with TSD. This method might also be useful to study potential brain regions associated with treatment response in patients with MDD.

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          Most cited references44

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          Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.

          Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.
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            Information-based functional brain mapping.

            The development of high-resolution neuroimaging and multielectrode electrophysiological recording provides neuroscientists with huge amounts of multivariate data. The complexity of the data creates a need for statistical summary, but the local averaging standardly applied to this end may obscure the effects of greatest neuroscientific interest. In neuroimaging, for example, brain mapping analysis has focused on the discovery of activation, i.e., of extended brain regions whose average activity changes across experimental conditions. Here we propose to ask a more general question of the data: Where in the brain does the activity pattern contain information about the experimental condition? To address this question, we propose scanning the imaged volume with a "searchlight," whose contents are analyzed multivariately at each location in the brain.
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              The subgenual anterior cingulate cortex in mood disorders.

              The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                17 July 2012
                : 7
                : 7
                : e40968
                Affiliations
                [1 ]Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
                [2 ]Mental Health Institute, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
                [3 ]Mental Health Center, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
                [4 ]School of Mathematical Sciences, University of Electronic Science and Technology of China, Chengdu, China
                [5 ]The Mood and Anxiety Clinic in the Mood Disorders Program of the Department of Psychiatry at Case Western Reserve University School of Medicine/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America
                [6 ]Department of Radiology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
                Institution of Automation, CAS, China
                Author notes

                Conceived and designed the experiments: FL WG CT ZL J. Zhao HC. Performed the experiments: WG CT ZL J. Zhao HC. Analyzed the data: FL DY J. Zhang HC. Contributed reagents/materials/analysis tools: FL WG DY QG ZX HD J. Zhao HC. Wrote the paper: FL WG DY QG ZX KG HC.

                Article
                PONE-D-11-23204
                10.1371/journal.pone.0040968
                3398877
                22815880
                1c29b811-dee2-4c5e-8fcc-9c1db319dfe5
                Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 22 November 2011
                : 19 June 2012
                Page count
                Pages: 11
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Neuroanatomy
                Neuroscience
                Neuroanatomy
                Medicine
                Clinical Research Design
                Statistical Methods
                Diagnostic Medicine
                Pathology
                General Pathology
                Biomarkers
                Epidemiology
                Biomarker Epidemiology
                Mental Health
                Psychiatry
                Mood Disorders
                Neuropsychiatric Disorders

                Uncategorized
                Uncategorized

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