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Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals

Title: Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals
Authors: Favre, P; Pauling, M; Stout, J; Hozer, F; Sarrazin, S; Abé, C; Alda, M; Alloza, C; Alonso-Lana, S; Andreassen, OA; Baune, BT; Benedetti, F; Busatto, GF; Canales-Rodríguez, EJ; Caseras, X; Chaim-Avancini, TM; Ching, CRK; Dannlowski, U; Deppe, M; Eyler, LT; Fatjo-Vilas, M; Foley, SF; Grotegerd, D; Hajek, T; Haukvik, UK; Howells, FM; Jahanshad, N; Kugel, H; Lagerberg, TV; Lawrie, SM; Linke, JO; McIntosh, A; Melloni, EMT; Mitchell, PB; Polosan, M; Pomarol-Clotet, E; Repple, J; Roberts, G; Roos, A; Rosa, PGP; Salvador, R; Sarró, S; Schofield, PR; Serpa, MH; Sim, K; Stein, DJ; Sussmann, JE; Temmingh, HS; Thompson, PM; Verdolini, N; Vieta, E; Wessa, M; Whalley, HC; Zanetti, MV; Leboyer, M; Mangin, JF; Henry, C; Duchesnay, E; Houenou, J
Source: urn:ISSN:0893-133X ; urn:ISSN:1740-634X ; Neuropsychopharmacology, 44, 13, 2285-2293
Publisher Information: Springer Nature
Publication Year: 2019
Collection: UNSW Sydney (The University of New South Wales): UNSWorks
Subject Terms: 5202 Biological Psychology; 32 Biomedical and Clinical Sciences; 52 Psychology; Bipolar Disorder; Mental Illness; Brain Disorders; Neurosciences; Serious Mental Illness; Clinical Research; Biomedical Imaging; Mental Health; Adult; Brain; Corpus Callosum; Diffusion Tensor Imaging; Female; Humans; Male; Neural Pathways; White Matter; ENIGMA Bipolar Disorder Working Group; anzsrc-for: 5202 Biological Psychology; anzsrc-for: 32 Biomedical and Clinical Sciences; anzsrc-for: 52 Psychology; anzsrc-for: 11 Medical and Health Sciences; anzsrc-for: 17 Psychology and Cognitive Sciences; anzsrc-for: 3209 Neurosciences
Description: Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R 2 = 0.041, P corr < 0.001) and cingulum (right: R 2 = 0.041, left: R 2 = 0.040, P corr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: https://hdl.handle.net/1959.4/unsworks_63298
DOI: 10.1038/s41386-019-0485-6
Availability: https://hdl.handle.net/1959.4/unsworks_63298; https://unsworks.unsw.edu.au/bitstreams/76da79a7-93d8-455a-b46e-6c3d893f5b23/download; https://doi.org/10.1038/s41386-019-0485-6
Rights: open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read
Accession Number: edsbas.87E0D247
Database: BASE