In vivo hippocampal subfield volumes in bipolar disorder—A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group,Human Brain Mapping

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In vivo hippocampal subfield volumes in bipolar disorder—A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group
Human Brain Mapping ( IF 3.5 ) Pub Date : 2020-10-19 , DOI: 10.1002/hbm.25249
Unn K Haukvik _{1,

2} , Tiril P Gurholt _{2,

3,

4} , Stener Nerland _{3,

4} , Torbjørn Elvsåshagen _{2,

5,

6} , Theophilus N Akudjedu _{7,

8} , Martin Alda _{9,

10} , Dag Alnaes _{2,

3} , Silvia Alonso-Lana ₁₁ , Jochen Bauer ₁₂ , Bernhard T Baune _{13,

14,

15} , Francesco Benedetti _{16,

17} , Michael Berk _{18,

19} , Francesco Bettella ₂ , Erlend Bøen ₂₀ , Caterina M Bonnín ₂₁ , Paolo Brambilla _{22,

23} , Erick J Canales-Rodríguez ₁₁ , Dara M Cannon ₇ , Xavier Caseras ₂₄ , Orwa Dandash _{25,

26} , Udo Dannlowski ₁₃ , Giuseppe Delvecchio ₂₃ , Ana M Díaz-Zuluaga ₂₇ , Theo G M van Erp _{28,

29} , Mar Fatjó-Vilas ₁₁ , Sonya F Foley ₃₀ , Katharina Förster ₁₃ , Janice M Fullerton _{31,

32} , José M Goikolea ₂₁ , Dominik Grotegerd ₁₃ , Oliver Gruber ₃₃ , Bartholomeus C M Haarman ₃₄ , Beathe Haatveit _{2,

3} , Tomas Hajek _{9,

10} , Brian Hallahan ₇ , Mathew Harris ₃₅ , Emma L Hawkins ₃₅ , Fleur M Howells _{36,

37} , Carina Hülsmann ₁₃ , Neda Jahanshad ₃₈ , Kjetil N Jørgensen _{3,

4} , Tilo Kircher _{39,

40} , Bernd Krämer ₃₃ , Axel Krug _{39,

40,

41} , Rayus Kuplicki ₄₂ , Trine V Lagerberg ₂ , Thomas M Lancaster _{30,

43} , Rhoshel K Lenroot _{31,

44,

45} , Vera Lonning _{3,

4} , Carlos López-Jaramillo _{27,

46} , Ulrik F Malt ₆ , Colm McDonald ₇ , Andrew M McIntosh ₃₅ , Genevieve McPhilemy ₇ , Dennis van der Meer _{3,

47} , Ingrid Melle _{2,

3} , Elisa M T Melloni _{16,

17} , Philip B Mitchell _{44,

48} , Leila Nabulsi ₇ , Igor Nenadić _{39,

40} , Viola Oertel ₄₉ , Lucio Oldani ₂₂ , Nils Opel ₁₃ , Maria C G Otaduy ₅₀ , Bronwyn J Overs ₃₁ , Julian A Pineda-Zapata _{27,

51} , Edith Pomarol-Clotet ₁₁ , Joaquim Radua _{52,

53,

54} , Lisa Rauer ₃₃ , Ronny Redlich ₁₃ , Jonathan Repple ₁₃ , Maria M Rive ₅₅ , Gloria Roberts _{44,

48} , Henricus G Ruhe _{55,

56,

57} , Lauren E Salminen ₃₈ , Raymond Salvador ₁₁ , Salvador Sarró ₁₁ , Jonathan Savitz _{42,

58} , Aart H Schene _{56,

57} , Kang Sim _{59,

60,

61} , Marcio G Soeiro-de-Souza ₆₂ , Michael Stäblein ₄₉ , Dan J Stein _{36,

37,

63} , Frederike Stein _{39,

40} , Christian K Tamnes _{2,

3,

4,

64} , Henk S Temmingh _{36,

65} , Sophia I Thomopoulos ₃₈ , Dick J Veltman _{66,

67} , Eduard Vieta ₆₈ , Lena Waltemate ₁₃ , Lars T Westlye _{2,

69} , Heather C Whalley ₃₅ , Philipp G Sämann ₇₀ , Paul M Thompson ₃₈ , Christopher R K Ching ₃₈ , Ole A Andreassen _{2,

3} , Ingrid Agartz _{3,

4,

71} ,

Affiliation

Department of Adult Mental Health, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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.
Institute of Medical Imaging & Visualisation, Faculty of Health & Social Sciences, Bournemouth University, Bournemouth, UK.
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
National Institute of Mental Health, Klecany, Czech Republic.
FIDMAG Germanes Hospitalàries Research Foundation, CIBERSAM, Barcelona, Spain.
Institute of Clinical Radiology, University of Münster, Münster, Germany.
Department of Psychiatry, University of Münster, Münster, Germany.
Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia.
Psychiatry and Clinical Psychobiology, Scientific Institute Ospedale San Raffaele, Milan, Italy.
University Vita-Salute San Raffaele, Milan, Italy.
Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Victoria, Australia.
Orygen, The National Centre of Excellence in Youth Mental Health and Centre for Youth Mental Health, the Department of Psychiatry and the Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Barcelona Bipolar Disorders and Depressive Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Brain, Mind and Society Research Hub, Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia.
Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Antioquia, Colombia.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA.
Center for the Neurobiology of Learning, University of California Irvine and Memory, Irvine, California, USA.
Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, UK.
Neuroscience Research Australia, Randwick, New South Wales, Australia.
School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa.
Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California, USA.
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
Center for Mind, Brain and Behavior (CMBB), Marburg, Germany.
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
School of Psychology, Bath University, Bath, UK.
School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
University of New Mexico, Albuquerque, New Mexico, USA.
Mood Disorders Program, Hospital Universitario San Vicente Fundación, Medellín, Antioquia, Colombia.
School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
Black Dog Institute, Sydney, New South Wales, Australia.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
LIM44, Department of Radiology and Oncology, University of São Paulo, São Paulo, Brazil.
Research Group, Instituto de Alta Tecnología Médica, Medellín, Antioquia, Colombia.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain.
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
Psychiatry, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Department of Psychiatry, Radboudumc, Nijmegen, The Netherlands.
Oxley College of Health Sciences, The University of Tulsa, Tulsa, Oklahoma, USA.
West Region/Institute of Mental Health, Singapore, Singapore.
Yong Loo Lin School of Medicine/National University of Singapore, Singapore, Singapore.
Lee Kong Chian School of Medicine/Nanyang Technological University, Singapore, Singapore.
Department of Psychiatry, Universidade de São Paulo, São Paulo, Brazil.
SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.
PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
General Adult Psychiatry Division, Valkenberg Hospital, Cape Town, Western Cape, South Africa.
Department of Psychiatry, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Department of Psychology, University of Oslo, Oslo, Norway.
Max Planck Institute of Psychiatry, Munich, Germany.
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = −0.20), cornu ammonis (CA)1 (d = −0.18), CA2/3 (d = −0.11), CA4 (d = −0.19), molecular layer (d = −0.21), granule cell layer of dentate gyrus (d = −0.21), hippocampal tail (d = −0.10), subiculum (d = −0.15), presubiculum (d = −0.18), and hippocampal amygdala transition area (d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

中文翻译：

双相情感障碍的体内海马亚区体积——通过元分析双相情感障碍工作组增强神经影像遗传学的大型分析

海马体由解剖学和功能上不同的亚区组成，这些亚区可能不同地参与双相情感障碍 (BD) 的病理生理学。在这里，我们，通过 Meta 分析双相情感障碍工作组增强神经影像遗传学，研究 BD 中的海马亚区容积。FreeSurfer 处理了来自全球 23 个地点的 4,698 人（BD = 1,472，健康对照 [HC] = 3,226）的 T1 加权磁共振成像扫描。我们使用线性混合效应模型和大型分析来研究 BD 和 HC 之间海马亚区体积的差异，然后分析临床特征和药物使用情况。BD 显示整个海马体的体积明显更小（Cohen's d = -0.20），cornu ammonis (CA)1 ( d = -0.18）、CA2/3（d = -0.11）、CA4（d = -0.19）、分子层（d = -0.21）、齿状回颗粒细胞层（d = -0.21）、海马尾（d = - 0.10)、下托 ( d = -0.15)、前托 ( d = -0.18)、海马杏仁核过渡区 ( d = −0.17) 与 HC 相比。与 HC 相比，锂用户没有表现出体积差异，而非用户则有。抗精神病药或抗癫痫药的使用与较小的体积相关。在这项迄今为止对 BD 中海马亚区最大的研究中，我们显示研究的 12 个亚区中有 9 个普遍减少。这些关联受到药物使用的调节，特别是锂使用者和 HC 之间缺乏差异支持锂在 BD 中可能具有保护作用。

更新日期：2020-10-19

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