Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.,Molecular Psychiatry

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Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2018-Apr-01 , DOI: 10.1038/mp.2017.73
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2} , L T Westlye _{3,

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4} , N Jahanshad ₁ , J W Cheung ₁ , C R K Ching _{1,

6} , A Versace ₇ , A C Bilderbeck ₈ , A Uhlmann _{9,

10} , B Mwangi ₁₁ , B Krämer ₁₂ , B Overs ₁₃ , C B Hartberg ₃ , C Abé ₁₄ , D Dima _{15,

16} , D Grotegerd ₁₇ , E Sprooten ₁₈ , E Bøen ₁₉ , E Jimenez ₂₀ , F M Howells ₉ , G Delvecchio ₂₁ , H Temmingh ₉ , J Starke ₉ , J R C Almeida ₂₂ , J M Goikolea ₂₀ , J Houenou _{23,

24} , L M Beard ₂₅ , L Rauer ₁₂ , L Abramovic ₂₆ , M Bonnin ₂₀ , M F Ponteduro ₁₆ , M Keil ₂₇ , M M Rive ₂₈ , N Yao _{29,

30} , N Yalin ₃₁ , P Najt ₃₂ , P G Rosa _{33,

34} , R Redlich ₁₇ , S Trost ₂₇ , S Hagenaars ₃₅ , S C Fears _{36,

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55} , C Simhandl ₅₆ , C McDonald ₃₂ , C Bourne _{8,

57} , D J Stein _{9,

10} , D H Wolf ₂₅ , D M Cannon ₃₂ , D C Glahn _{29,

30} , D J Veltman ₅₈ , E Pomarol-Clotet _{38,

39} , E Vieta ₂₀ , E J Canales-Rodriguez _{38,

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34} , G F Busatto _{33,

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30} , G M Goodwin ₈ , H Kugel ₆₁ , H C Whalley ₃₅ , H G Ruhe _{8,

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39} , M G Soeiro-de-Souza ₃₃ , M P Boks ₂₆ , M V Zanetti _{33,

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69} , M L Phillips ₇ , M J Kempton ₁₆ , M Bauer ₅₁ , M Landén _{14,

70} , N S Lawrence ₇₁ , N E M van Haren ₂₆ , N R Horn ₉ , N B Freimer ₇₂ , O Gruber ₁₂ , P R Schofield _{13,

63} , P B Mitchell ₆₀ , R S Kahn ₂₆ , R Lenroot _{13,

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19} , P M Thompson ₁ , O A Andreassen _{3,

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Affiliation

Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA.
Janssen Research & Development, San Diego, CA, USA.
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
Neuroscience Interdepartmental Graduate Program, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
University Department of Psychiatry and Oxford Health NHS Foundation Trust, University of Oxford, Oxford, UK.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
MRC Unit on Anxiety and Stress Disorders, Groote Schuur Hospital (J-2), University of Cape Town, Cape Town, South Africa.
UT Center of Excellence on Mood Disorders, Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany.
Neuroscience Research Australia, Sydney, NSW, Australia.
Department of Clinical Neuroscience, Osher Centre, Karolinska Institutet, Stockholm, Sweden.
Department of Psychology, City University London, London, UK.
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Psychiatry, University of Münster, Münster, Germany.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
Hospital Clinic, IDIBAPS, University of Barcelona, CIBERSAM, Barcelona, Spain.
IRCCS "E. Medea" Scientific Institute, San Vito al Tagliamento, Italy.
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
INSERM U955 Team 15 'Translational Psychiatry', University Paris East, APHP, CHU Mondor, Fondation FondaMental, Créteil, France.
NeuroSpin, UNIACT Lab, Psychiatry Team, CEA Saclay, Gif Sur Yvette, France.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Psychiatry, Yale University, New Haven, CT, USA.
Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
Centre for Affective Disorders, King's College London, London, UK.
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, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA.
West Los Angeles Veterans Administration, Los Angeles, CA, USA.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Laureate Institute for Brain Research, Tulsa, OK, USA.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Department of Adult Psychiatry, University of Oslo, Oslo, Norway.
Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
Academic Psychiatry and Northern Centre for Mood Disorders, Newcastle University/Northumberland Tyne & Wear NHS Foundation Trust, Newcastle, UK.
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA.
MMIL, Department of Radiology, University of California San Diego, San Diego, CA, USA.
Department of Cognitive Science, Neurosciences and Psychiatry, University of California, San Diego, San Diego, CA, USA.
Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Psychiatry, University of Adelaide, Adelaide, SA, Australia.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
Institut Pasteur, Unité Perception et Mémoire, Paris, France.
Bipolar Center Wiener Neustadt, Wiener Neustadt, Austria.
Department of Psychology & Counselling, Newman University, Birmingham, UK.
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
School of Psychiatry and Black Dog Institute, University of New South Wales, Sydney, NSW, Australia.
Department of Clinical Radiology, University of Münster, Münster, Germany.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Faculty of Community Medicine, The University of Tulsa, Tulsa, OK, USA.
Department of Radiology, University of São Paulo, São Paulo, Brazil.
LIM44-Laboratory of Magnetic Resonance in Neuroradiology, University of São Paulo, São Paulo, Brazil.
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the Gothenburg University, Goteborg, Sweden.
Department of Psychology, University of Exeter, Exeter, UK.
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
National Institute of Mental Health, Klecany, Czech Republic.
Division of Clinical Neuroscience, Department of Research and Education, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Janssen Research & Development, Titusville, NJ, USA.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10^-21), left fusiform gyrus (d=-0.288; P=8.25 × 10^-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10^-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

中文翻译：

双相情感障碍中的皮质异常：来自 ENIGMA 双相情感障碍工作组的 6503 名个体的 MRI 分析。

尽管进行了数十年的研究，但双相情感障碍 (BD) 的病理生理学仍未得到很好的理解。结构性大脑差异与 BD 相关，但神经影像学研究的结果并不一致。为了解决这个问题，我们对 6503 名个体的脑磁共振成像扫描进行了迄今为止规模最大的皮质灰质厚度和表面积测量研究，其中包括 1837 名无血缘关系的 BD 成人和 2582 名无血缘关系的健康对照组，同时还检查了常见的影响处方药、发病年龄、精神病史、情绪状态、皮质区域的年龄和性别差异。在BD中，两个大脑半球的额叶、颞叶和顶叶区域的皮质灰质较薄。BD 对左鳃盖肌的影响最强（Cohen's d=-0.293；^-21 )、左梭状回 (d=-0.288; P=8.25 × 10 ^-21 ) 和左额叶中额叶皮质 (d=-0.276; P=2.99 × 10 ^-19）。较长的疾病持续时间（考虑到扫描时的年龄）与额叶、内侧顶叶和枕叶区域的皮质厚度减少有关。我们发现，包括锂、抗癫痫药和抗精神病药在内的几种常用处方药与皮质厚度和表面积显着相关，即使在考虑了接受多种药物治疗的患者之后也是如此。我们发现皮质表面积减少与精神病史相关的证据，但与扫描时的情绪状态无关。我们的分析揭示了以前未检测到的关联，并对 BD 神经影像学研究中潜在的混杂变量进行了广泛分析。

更新日期：2018-03-22

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