What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group,Human Brain Mapping

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What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group
Human Brain Mapping ( IF 3.5 ) Pub Date : 2020-07-29 , DOI: 10.1002/hbm.25098
Christopher R K Ching ₁ , Derrek P Hibar ₂ , Tiril P Gurholt _{3,

4} , Abraham Nunes _{5,

6} , Sophia I Thomopoulos ₁ , Christoph Abé _{6,

7} , Ingrid Agartz _{3,

8,

9} , Rachel M Brouwer ₁₀ , Dara M Cannon ₁₁ , Sonja M C de Zwarte ₁₀ , Lisa T Eyler _{12,

13} , Pauline Favre _{14,

15} , Tomas Hajek _{4,

16} , Unn K Haukvik _{4,

17} , Josselin Houenou _{14,

15,

18} , Mikael Landén _{19,

20} , Tristram A Lett _{21,

22} , Colm McDonald ₁₀ , Leila Nabulsi _{1,

10} , Yash Patel ₂₃ , Melissa E Pauling _{13,

14} , Tomas Paus _{23,

24} , Joaquim Radua _{8,

25,

26,

27} , Marcio G Soeiro-de-Souza ₂₈ , Giulia Tronchin ₁₀ , Neeltje E M van Haren ₂₉ , Eduard Vieta _{25,

30} , Henrik Walter ₂₁ , Ling-Li Zeng _{1,

31} , Martin Alda ₄ , Jorge Almeida ₃₂ , Dag Alnaes ₃ , Silvia Alonso-Lana _{33,

34} , Cara Altimus ₃₅ , Michael Bauer ₃₆ , Bernhard T Baune _{37,

38,

39} , Carrie E Bearden _{40,

41} , Marcella Bellani ₄₂ , Francesco Benedetti _{43,

44} , Michael Berk _{45,

46} , Amy C Bilderbeck _{47,

48} , Hilary P Blumberg ₄₉ , Erlend Bøen ₅₀ , Irene Bollettini ₄₄ , Caterina Del Mar Bonnin _{25,

30} , Paolo Brambilla _{51,

52} , Erick J Canales-Rodríguez _{33,

34,

53,

54} , Xavier Caseras ₅₅ , Orwa Dandash _{56,

57} , Udo Dannlowski ₃₇ , Giuseppe Delvecchio ₅₁ , Ana M Díaz-Zuluaga ₅₈ , Danai Dima _{59,

60} , Édouard Duchesnay ₁₄ , Torbjørn Elvsåshagen _{17,

61,

62} , Scott C Fears _{63,

64} , Sophia Frangou _{65,

66} , Janice M Fullerton _{67,

68} , David C Glahn ₆₉ , Jose M Goikolea _{25,

30} , Melissa J Green _{67,

70} , Dominik Grotegerd ₃₇ , Oliver Gruber ₇₁ , Bartholomeus C M Haarman ₇₂ , Chantal Henry _{73,

74} , Fleur M Howells _{75,

76} , Victoria Ives-Deliperi ₇₅ , Andreas Jansen _{77,

78} , Tilo T J Kircher ₇₈ , Christian Knöchel ₇₉ , Bernd Kramer ₇₁ , Beny Lafer ₈₀ , Carlos López-Jaramillo _{58,

81} , Rodrigo Machado-Vieira ₈₂ , Bradley J MacIntosh _{83,

84} , Elisa M T Melloni _{43,

44} , Philip B Mitchell ₇₀ , Igor Nenadic ₇₈ , Fabiano Nery _{85,

86} , Allison C Nugent ₈₇ , Viola Oertel ₇₉ , Roel A Ophoff _{88,

89} , Miho Ota ₉₀ , Bronwyn J Overs ₆₇ , Daniel L Pham ₃₅ , Mary L Phillips ₉₁ , Julian A Pineda-Zapata ₉₂ , Sara Poletti _{43,

44} , Mircea Polosan _{93,

94} , Edith Pomarol-Clotet _{33,

34} , Arnaud Pouchon ₉₃ , Yann Quidé _{67,

70} , Maria M Rive ₉₅ , Gloria Roberts ₇₀ , Henricus G Ruhe _{96,

97} , Raymond Salvador _{33,

34} , Salvador Sarró _{33,

34} , Theodore D Satterthwaite ₉₈ , Aart H Schene ₉₆ , Kang Sim _{99,

100} , Jair C Soares _{101,

102} , Michael Stäblein ₇₉ , Dan J Stein _{75,

76,

103} , Christian K Tamnes _{3,

8,

104} , Georgios V Thomaidis _{105,

106} , Cristian Vargas Upegui ₅₈ , Dick J Veltman ₁₀₇ , Michèle Wessa ₁₀₈ , Lars T Westlye _{109,

110} , Heather C Whalley ₁₁₁ , Daniel H Wolf ₉₈ , Mon-Ju Wu ₁₀₂ , Lakshmi N Yatham ₁₁₂ , Carlos A Zarate _{113,

114} , Paul M Thompson ₁ , Ole A Andreassen _{3,

4} ,

Affiliation

Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Genentech, Inc., South San Francisco, California, USA.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addicition, Oslo University Hospital, Oslo, Norway.
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Center for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Psychiatry, University Medical Center Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
Department of Psychiatry, University of California, La Jolla, California, USA.
Desert-Pacific MIRECC, VA San Diego Healthcare, San Diego, California, USA.
INSERM U955, team 15 "Translational Neuro-Psychiatry", Créteil, France.
Neurospin, CEA Paris-Saclay, team UNIACT, Gif-sur-Yvette, France.
National Institute of Mental Health, Klecany, Czech Republic.
Norwegian Centre for Mental Disorders Research (NORMENT), Oslo University Hospital, Oslo, Norway.
APHP, Mondor University Hospitals, DMU IMPACT, Créteil, France.
Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department for Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurology with Experimental Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
Early Psychosis: Interventions and Clinical-detection (EPIC) lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Mood Disorders Unit (GRUDA), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Rotterdam, The Netherlands.
Barcelona Bipolar Disorders and Depressive Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
College of Intelligence Science and Technology, National University of Defense Technology, Changsha, China.
Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
CIBERSAM, Madrid, Spain.
Milken Institute Center for Strategic Philanthropy, Washington, District of Columbia, USA.
Department of Psychiatry and Psychotherapy, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Department of Psychiatry, University of Münster, Münster, Germany.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, USA.
Department of Psychology, University of California, Los Angeles, California, USA.
Section of Psychiatry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Division of Neuroscience, Psychiatry and Psychobiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
IMPACT Institute - The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia.
The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Orygen, Melbourne, Victoria, Australia.
P1vital Ltd, Wallingford, UK.
Department of Psychiatry, University of Oxford, Oxford, UK.
Mood Disorders Research Program, Yale School of Medicine, New Haven, Connecticut, USA.
Psychosomatic and CL Psychiatry, Oslo University Hospital, Oslo, Norway.
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Signal Processing Lab (LTS5), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia.
Brain, Mind and Society Research Hub, Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia.
Department of Psychology, School of Social Sciences and Arts, City, University of London, London, UK.
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Center for Neurobehavioral Genetics, Los Angeles, California, USA.
Greater Los Angeles Veterans Administration, Los Angeles, California, USA.
Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Neuroscience Research Australia, Randwick, New South Wales, Australia.
School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Department of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Psychiatry, Service Hospitalo-Universitaire, GHU Paris Psychiatrie & Neurosciences, Paris, France.
Université de Paris, Paris, France.
Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany.
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany.
Laboratory of Psychiatric Neuroimaging (LIM-21), Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Mood Disorders Program, Hospital Universitario Trastorno del Ánimo, Medellín, Colombia.
Experimental Therapeutics and Molecular Pathophysiology Program, Department of Psychiatry, UTHealth, University of Texas, Houston, Texas, USA.
Hurvitz Brain Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
University of Cincinnati, Cincinnati, Ohio, USA.
Universidade de São Paulo, São Paulo, SP, Brazil.
MEG Core Facility, Bethesda, Maryland, USA.
UCLA Center for Neurobehavioral Genetics, Los Angeles, California, USA.
Department of Psychiatry, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Research Group, Instituto de Alta Tecnología Médica (IATM), Medellín, Colombia.
University of Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France.
INSERM U1216 - Grenoble Institut des Neurosciences, La Tronche, France.
Department of Psychiatry, Amsterdam UMC, location AMC, Amsterdam, The Netherlands.
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
West Region, Institute of Mental Health, Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Center of Excellent on Mood Disorders, UTHealth Houston, Houston, Texas, USA.
Department of Psychiatry and Behavioral Sciences, UTHealth Houston, Houston, Texas, USA.
SAMRC Unit on Risk & Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
Papanikolaou General Hospital, Thessaloniki, Greece.
Laboratory of Mechanics and Materials, School of Engineering, Aristotle University, Thessaloniki, Greece.
Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands.
Department of Neuropsychology and Clinical Psychology, Johannes Gutenberg-University Mainz, Mainz, Germany.
Department of Psychology, University of Oslo, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Department of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
Chief Experimental Therapeutics & Pathophysiology Branch, Bethesda, Maryland, USA.
Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland, USA.

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.

中文翻译：

我们从大规模神经影像学中了解到双相情感障碍：ENIGMA 双相情感障碍工作组的发现和未来方向

MRI 衍生的大脑测量提供了基因、环境和行为之间的联系，并已在双相情感障碍 (BD) 中得到广泛研究。然而，许多双相情感障碍的神经影像学研究动力不足，导致结果各异且效果不确定。通过荟萃分析增强神经影像遗传学 (ENIGMA) 双相情感障碍工作组成立于 2012 年，旨在推动发现、达成共识研究结果并为未来的假设驱动型双相情感障碍研究提供信息。通过这项努力，来自 20 个国家和 55 个机构的 150 多名研究人员汇集了数据和资源，开展了有史以来最大规模的 BD 神经影像研究。 ENIGMA 双相情感障碍工作组应用标准化处理和分析技术来支持多模式脑 MRI 的大规模荟萃分析和大型分析，并提高将大脑变异与临床和遗传数据相关的研究的可重复性。 BD 工作组的初步研究揭示了与 BD 相关的较低皮质厚度、皮质下体积和破坏的白质完整性的普遍模式。研究结果还包括绘制锂盐等常见药物的大脑变化、症状模式和临床风险概况，并为双相情感障碍的病理生理机制提供了进一步的见解。在这里，我们讨论 BD 工作组的主要发现、其正在进行的项目以及大规模精神疾病合作研究的未来方向。

更新日期：2020-07-29

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