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What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group

HUMAN BRAIN MAPPING (2022)

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Journal

HUMAN BRAIN MAPPING
Volume 43, Issue 1, Pages 56-82

Publisher

WILEY
DOI: 10.1002/hbm.25098

Keywords

bipolar disorder; cortical surface area; cortical thickness; ENIGMA; mega-analysis; meta-analysis; MRI; neuroimaging; psychiatry; volume

Categories

Neurosciences Neuroimaging Radiology, Nuclear Medicine & Medical Imaging

Funding

  1. NIH Big Data to Knowledge (BD2K) program [U54 EB020403]
  2. ENIGMA World Aging Center [R56 AG058854]
  3. ENIGMA Sex Differences Initiative [R01 MH116147]
  4. Canadian Institutes of Health Research
  5. South-Eastern Norway Regional Health Authority [2019107, 2017112]
  6. South East Norway Health Authority
  7. EU CoMorMent grant
  8. NIH
  9. BMBF (Germany)
  10. Codi-University of Antioquia
  11. Italian Ministry of Health [GR-2010-2319022, RF-2011-02350980, RF-2011-02349921, RF-2016-02364582]
  12. European Union [EU-FP7-HEALTH-F2-2008-222963]
  13. National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship [APP1059660, APP1156072]
  14. AstraZeneca
  15. National Institute of Mental Health
  16. Internal Bipolar Disorder Foundation
  17. Brain and Behavior Research Foundation
  18. Oslo University Hospital
  19. Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III [PI15/00283]
  20. Fondo Europeo de Desarrollo Regional (FEDER) Funds from the European Commission (A Way of Making Europe)
  21. Departament de Salut de la Generalitat de Catalunya, , CERCA Programme/Generalitat de Catalunya [2017SGR1365, SLT002/16/00331, SLT006/17/00357]
  22. Generalitat de Catalunya [2017SGR01271]
  23. Instituto de Salud Carlos III - European Regional Development Fund/European Social Fund Investing in your future [CPII16/00018, CD16/00264, CD18/00029, PI15/00277, PI18/00810, PI18/00877]
  24. Health Research Board [HRB-HRA-POR-324, HRA_POR/2011/100]
  25. Irish Research Council (IRC) Postgraduate Scholarships
  26. NARSAD
  27. NIA [T32AG058507]
  28. NIH/NIMH [5T32MH073526]
  29. NIH from the Big Data to Knowledge (BD2K) Program [U54EB020403]
  30. German Research Foundation (DFG) [FOR2107 DA1151/5-1, DA1151/5-2, SFB-TRR58, CRC 636/C6, We3638/5-1]
  31. Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster [Dan3/012/17]
  32. PRISMA U.T Colciencias
  33. CODI-UdeA
  34. Bipli ANR
  35. Desert-Pacific MIRECC, NIH [MH083968]
  36. grant Infrastructure d'avenir en Biologie Sante [ANR-11-INBS-0006]
  37. Agence Nationale pour la Recherche [ANR-11-IDEX-0004 Labex BioPsy, ANR-10-COHO-10-01 psyCOH]
  38. Fondation pour la Recherche Medicale (Bioinformatique pour la biologie 2014)
  39. Fondation de l'Avenir (Recherche Medicale Appliquee 2014)
  40. Australian National Medical and Health Research Council (NHMRC) [1037196, 1066177, 1063960]
  41. Lansdowne Foundation
  42. Janette Mary O'Neil Research Fellowship
  43. CIHR
  44. Ontario Mental Health Foundation
  45. NHMRC [APP630471]
  46. Deutsche Forschungsgemeinschaft (DFG) via the Clinical Research Group 241 Genotype-phenotype relationships and neurobiology of the longitudinal course of psychosis [GR 1950/5-1, GR 1950/10-1, TP2]
  47. Research Council of Norway [223273, 288083, 230345, 249795]
  48. Canadian Institutes of Health Research [142255]
  49. Brain and Behavior Research Foundation (Independent Investigator Award) [23412]
  50. Ministry of Health of the Czech Republic [16-32791A, 16-32696A]
  51. KAKENHI [17K10287]
  52. South-Eastern Norway Health Authorities [2012-132]
  53. Norwegian Research Council [223273]
  54. University of Cape Town's Research Committee
  55. South African funding body the Medical Research Council
  56. South African funding body the National Research Foundation
  57. Deutsche Forschungsgemeinschaft, DFG [JA 1890/7-1, JA 1890/7-2]
  58. German Federal Ministry of Education and Research [01EE1404F]
  59. National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
  60. DFG grant [FOR 2107, KI 588/14-1, KI 588/14-2, DA 1151/5-1, DA 1151/5-2, KR 3822/5-1, KR 3822/7-2, NE 2254/1-2]
  61. Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and development, AMED [16dm0107100h0001]
  62. William K Warren Foundation
  63. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
  64. Swedish Research Council [2018-02653]
  65. Swedish foundation for Strategic Research [KF10-0039]
  66. Swedish Brain foundation
  67. Swedish Federal Government under the LUA/ALF [ALF 20170019, ALFGBG-716801]
  68. German Ministry for Education and Research (BMBF) grants NGFNplus MooDS [01GS08148]
  69. German Ministry for Education and Research (BMBF) e:Med program [O1ZX1314B, O1ZX1314G]
  70. German Ministry for Education and Research (BMBF) Forschungsnetz AERIAL [01EE1406A, 01EE1406B]
  71. NARSAD Distinguished Investigator Grant
  72. DFG [Wa 1539/11-1, ER 724/4-1]
  73. NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation
  74. NIHR Oxford Health Biomedical Research Centre
  75. Wellcome Centre for Integrative Neuroimaging
  76. Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
  77. KAKENHI from the Japan Society for the Promotion of Science [24591716, 15K09832]
  78. Wellcome Trust [104036/Z/14/Z, 216767/Z/19/Z]
  79. UKRI MRC [MC_PC_17209, MR/S035818/1]
  80. NIMH Intramural Research Program
  81. Nova Scotia Health Research Foundation
  82. Killam Trust
  83. Australian National Health and Medical Research Council [1037196, 1066177, 1063960, 510135]
  84. NSERC (CGS) scholarship
  85. Fondation pour la Recherche Medicale
  86. Natural Sciences and Engineering Research Council
  87. Pittsburgh Foundation
  88. Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Antioquia, Colombia
  89. DRCI CHU Grenoble
  90. Sante et Societe Federative Research Structure
  91. Instituto de Salud Carlos III [CPII16/00018, PI18/00810]
  92. Australian National Health and Medical Research Council of Australia (NHMRC) [APP630471, APP1081603]
  93. Macquarie University's ARC Centre of Excellence in Cognition and its Disorders [CE110001021]
  94. Spanish Ministry of Science, Innovation and Universities / Economy and Competitiveness/Instituto de Salud Carlos III [CPII19/00009]
  95. ERDF Funds from the European Commission (A Way of Making Europe)
  96. Netherlands Organization for Health Research and Development (ZonMw), program Mental Health, education of investigators in mental health (OOG) [100-002-034]
  97. Australian National Medical and Health Research Council [1037196]
  98. ZonMW Geestkracht OOG 2007 [100002034]
  99. NWO/ZonMW VENI grant [016.126.059]
  100. NARSAD [R01MH107703, K23MH098130]
  101. ZonMw
  102. NHG [SIG/12004]
  103. SBIC [RP C-009]
  104. NIMH [R01 MH085667]
  105. Dunn Foundation
  106. Pat Rutherford, Jr. Endowed Chair in Psychiatry
  107. German Research Council (DFG)
  108. German Ministry for Education and Research (BMBF
  109. Brain Imaging Center Frankfurt/Main) [DLR 01GO0203]
  110. Southern and Eastern Norway Regional Health Authority [2019069]
  111. National Research Foundation of South Africa
  112. Irish Research Council [GOIPG/2018/2464]
  113. European Research Council under the European Union's Horizon 2020 research and Innovation program (ERC StG) [802998]
  114. Wellcome Trust
  115. NIH [K23MH085096, R01MH101111]
  116. FAPESP-Brazil [2009/14891-9, 2010/18672-7, 2012/23796-2, 2013/03905-4]
  117. CNPq-Brazil [478466/2009, 480370/2009]
  118. Wellcome Trust (UK)
  119. Brain & Behavior Research Foundation (2010 NARSAD Independent Investigator Award)
  120. Intramural Research Program, National Institute of Mental Health
  121. National Natural Science Foundation of China [61722313]
  122. Fok Ying Tung Education Foundation [161057]
  123. Science & Technology Innovation Program of Hunan Province [2018RS3080]
  124. Colciencias
  125. Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP [24-11]
  126. Hersenstichting
  127. AMC Amsterdam
  128. University of Cape Town
  129. CERCA Programme/Generalitat de Catalunya
  130. CIBERSAM
  131. SA MRC
  132. [R01MH075007]
  133. [R01MH095454]
  134. [K23MH074644-01]
  135. [K08MH086786]
  136. [R03MH105808]
  137. [R01 MH080912]
  138. [R01 MH096957]
  139. [R01 MH106324]
  140. [EU-FP7-HEALTH-222963]
  141. [EU-FP7-PEOPLE- 286334]
  142. [5R01MH090553]
  143. [R37MH100041]
  144. [R01MH059929]
  145. [R01MH060952]
  146. [R01MH076971]
  147. [R21MH113871]
  148. [P20GM121312]
  149. [MH059929]
  150. [MH110420]
  151. Health Research Board (HRB) [HRA-POR-2011-100] Funding Source: Health Research Board (HRB)
  152. MRC [MR/S035818/1, MC_PC_17209] Funding Source: UKRI
  153. NATIONAL INSTITUTE OF MENTAL HEALTH [ZICMH002889, ZIAMH002927, ZIAMH002857] Funding Source: NIH RePORTER
  154. Grants-in-Aid for Scientific Research [24591716, 17K10287] Funding Source: KAKEN

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MRI-derived brain measures have been widely studied in bipolar disorder (BD) and provide insights into the connections between genes, the environment, and behavior. The ENIGMA Bipolar Disorder Working Group is a collaborative effort that aims to generate consensus findings and improve the replicability of studies on BD. Through large-scale neuroimaging studies, the working group has discovered patterns of brain alterations associated with BD, as well as the effects of medications and clinical risk profiles.
MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

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