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

Author(s):Show less -

Favre, Pauline ^{[1, 2]} ; Pauling, Melissa ^{[1, 2]} ; Stout, Jacques ^[1] ; Hozer, Franz ^{[1, 2, 3, 4]} ; Sarrazin, Samuel ^{[1, 2, 5, 6]} ; Abe, Christoph ^[7] ; Alda, Martin ^[8] ; Alloza, Clara ^{[9, 10]} ; Alonso-Lana, Silvia ^{[11, 12]} ; Andreassen, Ole A. ^{[13, 14]} ; Baune, Bernhard T. ^{[15, 16]} ; Benedetti, Francesco ^{[17, 18]} ; Busatto, Geraldo F. ^{[19, 20]} ; Canales-Rodriguez, Erick J. ^[12] ; Caseras, Xavier ^[21] ; Chaim-Avancini, Tiffany Moukbel ^{[19, 20]} ; Ching, Christopher R. K. ^{[22, 23]} ; Dannlowski, Udo ^[15] ; Deppe, Michael ^[24] ; Eyler, Lisa T. ^{[25, 26]} ; Fatjo-Vilas, Mar ^{[11, 12]} ; Foley, Sonya F. ^[27] ; Grotegerd, Dominik ^[15] ; Hajek, Tomas ^[8] ; Haukvik, Unn K. ^{[13, 14]} ; Howells, Fleur M. ^{[28, 29]} ; Jahanshad, Neda ^[22] ; Kugel, Harald ^[30] ; Lagerberg, Trine V. ^{[13, 14]} ; Lawrie, Stephen M. ^[31] ; Linke, Julia O. ^{[32, 33]} ; McIntosh, Andrew ^{[34, 31]} ; Melloni, Elisa M. T. ^{[18, 35]} ; Mitchell, Philip B. ^{[36, 37]} ; Polosan, Mircea ^[38] ; Pomarol-Clotet, Edith ^{[11, 12]} ; Repple, Jonathan ^[15] ; Roberts, Gloria ^{[36, 37]} ; Roos, Annerine ^[39] ; Rosa, Pedro G. P. ^{[19, 20]} ; Salvador, Raymond ^{[11, 27]} ; Sarro, Salvador ^{[11, 27]} ; Schofield, Peter R. ^{[40, 41]} ; Serpa, Mauricio H. ^{[17, 18]} ; Sim, Kang ^{[42, 43, 44]} ; Stein, Dan J. ^[39] ; Sussmann, Jess E. ^[31] ; Temmingh, Henk S. ^{[28, 45]} ; Thompson, Paul M. ^[23] ; Verdolini, Norma ^{[11, 12, 46]} ; Vieta, Eduard ^{[11, 46]} ; Wessa, Michele ^[32] ; Whalley, Heather C. ^[32] ; Zanetti, Marcus V. ^{[47, 18, 20]} ; Leboyer, Marion ^{[1, 48, 49]} ; Mangin, Jean-Francois ^[1] ; Henry, Chantal ^[50] ; Duchesnay, Edouard ^[1] ; Houenou, Josselin ^{[1, 2, 48, 49]} ; Working, ENIGMA Bipolar Disorder

Affiliation:Show less -

^[1] Univ Paris Saclay, CEA, Neurospin, Gif Sur Yvette - France

^[2] INSERM, Unit U955, Team 15, Translat Psychiat, Creteil - France

^[3] Corentin Celton Hosp, AP HP, Dept Psychiat, Issy Les Moulineaux - France

^[4] Paris Descartes Univ, PRES Sorbonne Paris Cite, Paris - France

^[5] Hop Univ Mondor, Pole Psychiat, DHU PePSY, Creteil - France

^[6] Fondat Falret, Bipol Falret, St Ouen - France

^[7] Karolinska Inst, Clin Neurosci, Stockholm - Sweden

^[8] Dalhousie Univ, Dept Psychiat, Halifax, NS - Canada

^[9] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian - Scotland

^[10] Hosp Gen Univ Gregorio Maranon, IISGM, Dept Child & Adolescent Psychiat, Madrid - Spain

^[11] CIBERSAM, Barcelona - Spain

^[12] FIDMAG Res Fdn, Barcelona - Spain

^[13] Univ Oslo, Dept Mental Hlth & Addict, Oslo - Norway

^[14] Oslo Univ Hosp, NORMENT KG Jebsen Ctr Psychosis Res, Oslo - Norway

^[15] Univ Munster, Dept Psychiat, Munster - Germany

^[16] Univ Melbourne, Dept Psychiat, Melbourne, Vic - Australia

^[17] Ist Sci San Raffaele, Div Neurosci, Milan - Italy

^[18] Univ Vita Salute San Raffaele, Milan - Italy

^[19] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo, SP - Brazil

^[20] Univ Sao Paulo, Dept & Inst Psiquiatria, Hosp Clin HCFMUSP, Lab Psychiat Neuroimaging LIM 21, Fac Med, Sao Paulo, SP - Brazil

^[21] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam - Wales

^[22] Univ Calif Los Angeles, Interdept Neurosci Program, Los Angeles, CA - USA

^[23] Univ Southern Calif, Keck Sch Med USC, Mark & Mary Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Los Angeles, CA 90007 - USA

^[24] Univ Munster, Dept Neurol, Munster - Germany

^[25] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 - USA

^[26] VA San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, La Jolla, CA - USA

^[27] Cardiff Univ, CUBRIC, Cardiff, S Glam - Wales

^[28] Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town - South Africa

^[29] Univ Cape Town, Inst Neurosci, Cape Town - South Africa

^[30] Univ Munster, Inst Clin Radiol, Munster - Germany

^[31] Royal Edinburgh & Associated Hosp, Dept Psychiat, Edinburgh, Midlothian - Scotland

^[32] Johannes Gutenberg Univ Mainz, Dept Clin Psychol & Neuropsychol, Mainz - Germany

^[33] NIMH, Emot & Dev Branch, Bethesda, MD 20892 - USA

^[34] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian - Scotland

^[35] Sci Inst, Div Neurosci, Psychiat & Clin Psychobiol, Milan - Italy

^[36] Black Dog Inst, Sydney, NSW - Australia

^[37] Univ New South Wales, Sch Psychiat, Sydney, NSW - Australia

^[38] Univ Grenoble Alpes, CHU Grenoble Alpes, Grenoble Inst Neurosci, INSERM, U1216, Grenoble - France

^[39] Univ Cape Town, SAMRC Unit Risk & Resilience Mental Disorders, Dept Psychiat, Cape Town - South Africa

^[40] Neurosci Res Australia, Sydney, NSW - Australia

^[41] Univ New South Wales, Sch Med Sci, Sydney, NSW - Australia

^[42] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore - Singapore

^[43] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore - Singapore

^[44] Inst Mental Hlth, West Reg, Singapore - Singapore

^[45] Valkenberg Hosp, Cape Town - South Africa

^[46] Univ Barcelona, IDIBAPS, Hosp Clin, Inst Neurosci, Barcelona - Spain

^[47] Hosp Sirio Libanes, Sao Paulo, SP - Brazil

^[48] CHU Mondor, AP HP, Dept Psychiat, Creteil - France

^[49] Univ Paris Est Creteil, Fac Med, Creteil - France

^[50] Inst Pasteur, Unite Percept & Memoire, Paris - France

• Document type: Journal article
• Source: NEUROPSYCHOPHARMACOLOGY; v. 44, n. 13, p. 2285-2293, DEC 2019.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 10/18672-7 - SPECGENE: genetic association study between single nucleotide polymorphisms of GAD1 and reelin and magnetic ressonance spectroscopy in bipolar I
• Grantee: Ricardo Alberto Moreno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/23796-2 - "Genetic association study between cognitive performance, polymorphisms of GAD1/Reelin and 3T magnetic ressonance spectroscopy of GABA/glutamate in bipolar I disorder and healthy controls"
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/03905-4 - NEUROBIOLOGICAL DIFFERENCES BETWEEN TREATMENT-NAIVE PATIENTS WITH BIPOLAR DISORDER SUBTYPES I AND II
• Grantee: Marcus Vinicius Zanetti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/14891-9 - Longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant
• Grantee: Rodrigo Machado-Vieira
• Support Opportunities: Research Grants - Young Investigators Grants