Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.
Journal: Molecular psychiatry
Volume: 23
Issue: 4
Year of Publication: 2019
Affiliated Institutions:
Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging & Informatics, University of Southern California, Marina del Rey, CA, USA.
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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.
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.
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 U Team 'Translational Psychiatry', University Paris East, APHP, CHU Mondor, Fondation FondaMental, Créteil, France.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
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.
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.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry, University of California, Los Angeles, Los Angeles, CA, USA.
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Department of Psychiatry, Radboud University Medical Center, 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 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.
Bipolar Center Wiener Neustadt, Wiener Neustadt, Austria.
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
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 Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Laureate Institute for Brain Research, Tulsa, OK, USA.
Department of Radiology, University of São Paulo, São Paulo, Brazil.
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
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.
Division of Clinical Neuroscience, Department of Research and Education, Oslo University Hospital, Oslo, Norway.
Janssen Research & Development, Titusville, NJ, USA.
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Abstract summary
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), left fusiform gyrus (d=-0.288; P=8.25 × 10) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10). 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.
Authors & Co-authors:
Hibar D P DP
Westlye L T LT
Doan N T NT
Jahanshad N N
Cheung J W JW
Ching C R K CRK
Versace A A
Bilderbeck A C AC
Uhlmann A A
Mwangi B B
Krämer B B
Overs B B
Hartberg C B CB
Abé C C
Dima D D
Grotegerd D D
Sprooten E E
Bøen E E
Jimenez E E
Howells F M FM
Delvecchio G G
Temmingh H H
Starke J J
Almeida J R C JRC
Goikolea J M JM
Houenou J J
Beard L M LM
Rauer L L
Abramovic L L
Bonnin M M
Ponteduro M F MF
Keil M M
Rive M M MM
Yao N N
Yalin N N
Najt P P
Rosa P G PG
Redlich R R
Trost S S
Hagenaars S S
Fears S C SC
Alonso-Lana S S
van Erp T G M TGM
Nickson T T
Chaim-Avancini T M TM
Meier T B TB
Elvsåshagen T T
Haukvik U K UK
Lee W H WH
Schene A H AH
Lloyd A J AJ
Young A H AH
Nugent A A
Dale A M AM
Pfennig A A
McIntosh A M AM
Lafer B B
Baune B T BT
Ekman C J CJ
Zarate C A CA
Bearden C E CE
Henry C C
Simhandl C C
McDonald C C
Bourne C C
Stein D J DJ
Wolf D H DH
Cannon D M DM
Glahn D C DC
Veltman D J DJ
Pomarol-Clotet E E
Vieta E E
Canales-Rodriguez E J EJ
Nery F G FG
Duran F L S FLS
Busatto G F GF
Roberts G G
Pearlson G D GD
Goodwin G M GM
Kugel H H
Whalley H C HC
Ruhe H G HG
Soares J C JC
Fullerton J M JM
Rybakowski J K JK
Savitz J J
Chaim K T KT
Fatjó-Vilas M M
Soeiro-de-Souza M G MG
Boks M P MP
Zanetti M V MV
Otaduy M C G MCG
Schaufelberger M S MS
Alda M M
Ingvar M M
Phillips M L ML
Kempton M J MJ
Bauer M M
Landén M M
Lawrence N S NS
van Haren N E M NEM
Horn N R NR
Freimer N B NB
Gruber O O
Schofield P R PR
Mitchell P B PB
Kahn R S RS
Lenroot R R
Machado-Vieira R R
Ophoff R A RA
Sarró S S
Frangou S S
Satterthwaite T D TD
Hajek T T
Dannlowski U U
Malt U F UF
Arolt V V
Gattaz W F WF
Drevets W C WC
Caseras X X
Agartz I I
Thompson P M PM
Andreassen O A OA
Study Outcome
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