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      Microstructural white matter abnormalities in pediatric and adult obsessive‐compulsive disorder: A systematic review and meta‐analysis

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          Abstract

          Objective

          To identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive‐compulsive disorder (OCD) in tract‐based spatial statistics (TBSS) studies.

          Methods

          We reviewed previous TBSS studies ( n = 20) in OCD and performed a meta‐analysis ( n = 16) of FA differences.

          Results

          No between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation.

          Conclusions

          Absent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto‐striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness.

          Abstract

          No between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence is seemingly related to an altered trajectory of brain maturation.

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          Most cited references81

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          Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

          There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.
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            The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication.

            Despite significant advances in the study of obsessive-compulsive disorder (OCD), important questions remain about the disorder's public health significance, appropriate diagnostic classification, and clinical heterogeneity. These issues were explored using data from the National Comorbidity Survey Replication, a nationally representative survey of US adults. A subsample of 2073 respondents was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing obsessions or compulsions at some time in their lives. While conditional probability of OCD was strongly associated with the number of obsessions and compulsions reported, only small proportions of respondents met full DSM-IV criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with substantial comorbidity, not only with anxiety and mood disorders but also with impulse-control and substance use disorders. Severity of OCD, assessed by an adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with poor insight, high comorbidity, high role impairment, and high probability of seeking treatment. The high prevalence of subthreshold OCD symptoms may help explain past inconsistencies in prevalence estimates across surveys and suggests that the public health burden of OCD may be greater than its low prevalence implies. Evidence of a preponderance of early onset cases in men, high comorbidity with a wide range of disorders, and reliable associations between disorder severity and key outcomes may have implications for how OCD is classified in DSM-V.
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              Diffusion tensor imaging of the brain.

              Diffusion tensor imaging (DTI) is a promising method for characterizing microstructural changes or differences with neuropathology and treatment. The diffusion tensor may be used to characterize the magnitude, the degree of anisotropy, and the orientation of directional diffusion. This review addresses the biological mechanisms, acquisition, and analysis of DTI measurements. The relationships between DTI measures and white matter pathologic features (e.g., ischemia, myelination, axonal damage, inflammation, and edema) are summarized. Applications of DTI to tissue characterization in neurotherapeutic applications are reviewed. The interpretations of common DTI measures (mean diffusivity, MD; fractional anisotropy, FA; radial diffusivity, D(r); and axial diffusivity, D(a)) are discussed. In particular, FA is highly sensitive to microstructural changes, but not very specific to the type of changes (e.g., radial or axial). To maximize the specificity and better characterize the tissue microstructure, future studies should use multiple diffusion tensor measures (e.g., MD and FA, or D(a) and D(r)).
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                Author and article information

                Contributors
                charlie_lee@qq.com
                qiyonggong@hmrrc.org.cn
                Journal
                Brain Behav
                Brain Behav
                10.1002/(ISSN)2157-9032
                BRB3
                Brain and Behavior
                John Wiley and Sons Inc. (Hoboken )
                2162-3279
                03 December 2020
                February 2021
                : 11
                : 2 ( doiID: 10.1002/brb3.v11.2 )
                : e01975
                Affiliations
                [ 1 ] Huaxi MR Research Center (HMRRC), Department of Radiology West China Hospital of Sichuan University Chengdu China
                [ 2 ] Research Unit of Psychoradiology Chinese Academy of Medical Sciences Chengdu China
                [ 3 ] Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University Chengdu China
                [ 4 ] Medical Imaging Technology Department, West China School of Medicine Sichuan University Chengdu China
                [ 5 ] Department of Psychiatry University of Cincinnati Cincinnati OH USA
                Author notes
                [*] [* ] Correspondence

                Fei Li and Qiyong Gong, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, No. 37 Guo Xue Lane, Chengdu 610041, Sichuan, China.

                Emails: charlie_lee@ 123456qq.com ; qiyonggong@ 123456hmrrc.org.cn

                Author information
                https://orcid.org/0000-0002-4737-5710
                Article
                BRB31975
                10.1002/brb3.1975
                7882176
                33270358
                898e7c55-38f0-4344-bb59-fea03e55a9eb
                © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 August 2020
                : 09 November 2020
                : 15 November 2020
                Page count
                Figures: 4, Tables: 3, Pages: 15, Words: 11417
                Funding
                Funded by: National Natural Science Foundation
                Award ID: 81621003
                Award ID: 81761128023
                Award ID: 81820108018
                Award ID: 82027808
                Award ID: 81401396
                Funded by: Sichuan Science and Technology Program
                Award ID: 2019YJ0098
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:14.02.2021

                Neurosciences
                psychoradiology,fractional anisotropy,meta‐analysis,obsessive‐compulsive disorder,rrid:scr_002823,rrid:scr_002554,tract‐based spatial statistics,white matter microstructure

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