Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals
Year: 2019
Type: article
Abstract: 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.
Source: Neuropsychopharmacology
Authors: for the ENIGMA Bipolar Disorder Working Group, Pauline Favre, Melissa Pauling, Jacques Stout, Franz Hozer, Samuel Sarrazin, Christoph Abé, Martin Alda, Clara Alloza, Silvia Alonso-Lana, Ole A. Andreassen, Bernhard T. Baune, Francesco Benedetti, Geraldo F. Busatto, Erick J. Canales-Rodríguez, Xavier Caseras, Tiffany Moukbel Chaim-Avancini, Christopher R. K. Ching, Udo Dannlowski, Michael Deppe, Lisa T. Eyler, Mar Fatjo-Vilas, Sonya F. Foley, Dominik Grotegerd, Tomas Hajek, Unn K. Haukvik, Fleur M. Howells, Neda Jahanshad, Harald Kugel, Trine V. Lagerberg, Stephen M. Lawrie, Julia O. Linke, Andrew McIntosh, Elisa M. T. Melloni, Philip B. Mitchell, Mircea Polosan, Edith Pomarol-Clotet, Jonathan Repple, Gloria Roberts, Annerine Roos, Pedro G. P. Rosa, Raymond Salvador, Salvador Sarró, Peter R. Schofield, Mauricio H. Serpa, Kang Sim, Dan J. Stein, Jess E. Sussmann, Henk S. Temmingh, Paul M. Thompson, Norma Verdolini, Eduard Vieta, Michele Wessa, Heather C. Whalley, Marcus V. Zanetti, Marion Leboyer, Jean-François Mangin, Chantal Henry, Edouard Duchesnay, Josselin Houenou
Institutions: Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, CEA Paris-Saclay, Inserm, CEA Paris-Saclay - Etablissement de Saclay, Sorbonne Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Corentin-Celton, Université Paris Descartes, Karolinska Institutet, Hôpitaux Universitaires Henri-Mondor, Dalhousie University, University of Edinburgh, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, University of Oslo, Centro de Investigación Biomédica en Red de Salud Mental, Oslo University Hospital, The University of Melbourne, University of Münster, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Cardiff University, University of California, Los Angeles, University of Southern California, University of California San Diego, VA San Diego Healthcare System, University of Cape Town, Royal Edinburgh Hospital, Johannes Gutenberg University Mainz, National Institute of Mental Health, UNSW Sydney, Black Dog Institute, Grenoble Institute of Neurosciences, Université Grenoble Alpes, South African Medical Research Council, Neuroscience Research Australia, Institute of Mental Health, National University of Singapore, Nanyang Technological University, Valkenberg Hospital, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Hospital Sírio-Libanês, Université Paris-Est Créteil, Institut Pasteur
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,760
Funders: Sanofi, Biogen, Fondation de l'Avenir pour la Recherche Médicale Appliquée, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Royal College of Physicians of Edinburgh, Ministerio de Ciencia, Innovación y Universidades, Centres de Recerca de Catalunya, Nova Scotia Health Research Foundation, European Commission, University of Edinburgh, South African Medical Research Council, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Fundação de Amparo à Pesquisa do Estado de São Paulo, Generalitat de Catalunya, Fondation pour la Recherche Médicale, Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya, Dainippon Sumitomo Pharma, Dalhousie University, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universitetet i Oslo, Norges Forskningsråd, Centro de Investigación Biomédica en Red de Salud Mental, H. Lundbeck A/S, National Institutes of Health, Allergan, Canadian Institutes of Health Research, Medical Research Council, Instituto de Salud Carlos III, European Regional Development Fund, National Center for Mental Health, National Institute on Aging, National Institute of Mental Health, National Institute of Biomedical Imaging and Bioengineering, NIH Clinical Center
Awards: Hospital Alerting Via Electronic Noticeboard (HAVEN), G109340971, The Human Brain Project, G1116979012, G1154649974, G1157805208, G1197468363, G119964413, G1216156242, G1255536505, G1269780614, G1280578974, SPECGENE: genetic association study between single nucleotide polymorphisms of GAD1 and reelin and magnetic ressonance spectroscopy in bipolar I, Implicación de variantes del gen DDR1 en la integridad de la mielina y en la velocidad de procesamiento cognitivo en pacientes con trastorno bipolar en fase eutímica, G1423865221, Laboratoire de Psychiatrie Biologique, G1552314173, G1793251574, G179444772, G1841685900, G1935761306, G195474297, G2038050771, G2108489402, G2163292895, G238323396, G265847165, G2831939486, G290699439, G29319320, G2933281967, G2973790809, G3108940385, G3138944228, G3146259446, G3160699921, IMAging GEnetics for MENtal Disorders, G3207356259, G3230416436, G3239377387, G3277956970, G3281292808, G3283395618, G3288897321, G3433676821, G3455626259, G3615139234, G3637334605, G3650402215, G3714203978, G3781777374, G3789307285, G3899763717, G3926333944, G393177772, G3934624715, G398641320, G4089841571, G4175096997, G4261582792, Stratifying Resilience and Depression Longitudinally (STRADL), G434337789, G4404744657, FondaMental-Cohortes, G4519315536, G4616268170, G4760961572, Development of Bosnia and Herzegovina's Network of Mobility Centres, G4846986379, G4866930200, G490900884, G4914386182, G496129201, G5012954570, G5030363304, G5038461968, G5069901229, G5182135128, G5232051750, G5328306480, G5368093169, G5702163051, Human Brain Project Specific Grant Agreement 2, G5796154708, G5802621812, G5824196655, G5840703522, G5885064267, User-friendly ICT tools to enhance self-management and effective treatment of depression in the EU, G6085389302, G6104069830, G6105316060, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G6125999700, G6224231191, G6345242356, G6346237422, G648958512, G6493800209, France Life Imaging, G656100070, Sorbonne Universités à Paris pour l'Enseignement et la Recherche, G6680420078, G6733821374, G675246756, G6794951016, G68579704, G698350584, G700495459, G7205418604, G7240651115, G7270624644, G7326177208, G7341669135, G7497706539, G7548641857, G778464899, G780302099, G790157075, G7934779123, G8267165792, G8270261256, G8524812431, A global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA Consortium, G8600254050, G8858095331, G8994360641, G9000003939, G9000008536, G9000060504, G9000106822, G9000210308, G9000216424, G9000250461, G9000280126, G961545024
OpenAlex ID: W2969721658