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      Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning

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          Abstract

          Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

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          Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.

          Little is known about lifetime prevalence or age of onset of DSM-IV disorders. To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
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            Emotional processing in anterior cingulate and medial prefrontal cortex.

            Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal-caudal cognitive and ventral-rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal-caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral-rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions. Published by Elsevier Ltd.
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              An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets.

              Analysis and interpretation of functional MRI (fMRI) data have traditionally been based on identifying areas of significance on a thresholded statistical map of the entire imaged brain volume. This form of analysis can be likened to a "fishing expedition." As we become more knowledgeable about the structure-function relationships of different brain regions, tools for a priori hypothesis testing are needed. These tools must be able to generate region of interest masks for a priori hypothesis testing consistently and with minimal effort. Current tools that generate region of interest masks required for a priori hypothesis testing can be time-consuming and are often laboratory specific. In this paper we demonstrate a method of hypothesis-driven data analysis using an automated atlas-based masking technique. We provide a powerful method of probing fMRI data using automatically generated masks based on lobar anatomy, cortical and subcortical anatomy, and Brodmann areas. Hemisphere, lobar, anatomic label, tissue type, and Brodmann area atlases were generated in MNI space based on the Talairach Daemon. Additionally, we interfaced these multivolume atlases to a widely used fMRI software package, SPM99, and demonstrate the use of the atlas tool with representative fMRI data. This tool represents a necessary evolution in fMRI data analysis for testing of more spatially complex hypotheses.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                March 2015
                17 March 2015
                : 5
                : 3
                : e530
                Affiliations
                [1 ]Division of Psychology, Department of Behavioural Sciences and Learning, Linköping University , Linköping, Sweden
                [2 ]Department of Psychology, Uppsala University , Uppsala, Sweden
                [3 ]Centre for Population Studies, Ageing and Living Conditions, Umeå University , Umeå, Sweden
                [4 ]Umeå Center for Functional Brain Imaging (UFBI), Umeå University , Umeå, Sweden
                [5 ]Donders Institute for Brain, Cognition and Behaviour, Radboud University , Nijmegen, The Netherlands
                [6 ]Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London , London, UK
                [7 ]Department of Psychology, Stockholm University , Stockholm, Sweden
                [8 ]Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet , Stockholm, Sweden
                Author notes
                [* ]MSc, Division of Psychology, Department of Behavioural Sciences and Learning, Linköping University , Linköping SE-581 83, Sweden. E-mail: kristoffer.nt.mansson@ 123456liu.se
                Author information
                http://orcid.org/0000-0003-2516-9075
                Article
                tp201522
                10.1038/tp.2015.22
                4354352
                6534b330-6a91-4e40-8214-99e72199a29c
                Copyright © 2015 Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 19 August 2014
                : 13 January 2015
                : 20 January 2015
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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