Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
Year: 2017
Type: article
Study design: Observational Study
Abstract: 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.
Source: Molecular Psychiatry
DOI: 10.1038/mp.2017.73
Authors: for the ENIGMA Bipolar Disorder Working Group, D P Hibar, L T Westlye, N T Doan, N Jahanshad, J W Cheung, C R K Ching, A Versace, A C Bilderbeck, A Uhlmann, B Mwangi, B Krämer, B Overs, C B Hartberg, C Abé, D Dima, D Grotegerd, E Sprooten, E Bøen, E Jimenez, F M Howells, G Delvecchio, H Temmingh, J Starke, J R C Almeida, J M Goikolea, J Houenou, L M Beard, L Rauer, L Abramovic, M Bonnin, M F Ponteduro, M Keil, M M Rive, N Yao, N Yalin, P Najt, P G Rosa, R Redlich, S Trost, S Hagenaars, S C Fears, S Alonso-Lana, T G M van Erp, T Nickson, T M Chaim-Avancini, T B Meier, T Elvsåshagen, U K Haukvik, W H Lee, A H Schene, A J Lloyd, A H Young, A Nugent, A M Dale, A Pfennig, A M McIntosh, B Lafer, B T Baune, C J Ekman, C A Zarate, C E Bearden, C Henry, C Simhandl, C McDonald, C Bourne, D J Stein, D H Wolf, D M Cannon, D C Glahn, D J Veltman, E Pomarol-Clotet, E Vieta, E J Canales-Rodriguez, F G Nery, F L S Duran, G F Busatto, G Roberts, G D Pearlson, G M Goodwin, H Kugel, H C Whalley, H G Ruhe, J C Soares, J M Fullerton, J K Rybakowski, J Savitz, K T Chaim, M Fatjó-Vilas, M G Soeiro-de-Souza, M P Boks, M V Zanetti, M C G Otaduy, M S Schaufelberger, M Alda, M Ingvar, M L Phillips, M J Kempton, M Bauer, M Landén, N S Lawrence, N E M van Haren, N R Horn, N B Freimer, O Gruber, P R Schofield, P B Mitchell, R S Kahn, R Lenroot, R Machado-Vieira, R A Ophoff, S Sarró, S Frangou, T D Satterthwaite, T Hajek, U Dannlowski, U F Malt, V Arolt, W F Gattaz, W C Drevets, X Caseras, I Agartz, P M Thompson, O A Andreassen
Institutions: University of Southern California, Oslo University Hospital, University of Oslo, University of California, Los Angeles, University of Pittsburgh, Oxford Health NHS Foundation Trust, University of Oxford, University of Cape Town, Groote Schuur Hospital, The University of Texas Health Science Center at Houston, Heidelberg University, Neuroscience Research Australia, Karolinska Institutet, City, University of London, King's College London, University of Münster, Icahn School of Medicine at Mount Sinai, Diakonhjemmet Hospital, Centro de Investigación Biomédica en Red de Salud Mental, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, IRCCS Eugenio Medea, Brown University, Inserm, Fondation FondaMental, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Paris-Saclay, University of Pennsylvania, University Medical Center Utrecht, Universitätsmedizin Göttingen, University of Göttingen, Amsterdam UMC Location University of Amsterdam, University of Amsterdam, Hartford Hospital, Yale University, Ollscoil na Gaillimhe – University of Galway, Universidade de São Paulo, University of Edinburgh, Fidmag Sisters Hospitallers, University of California, Irvine, Medical College of Wisconsin, Laureate Institute for Brain Research, Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle University, National Institutes of Health, National Institute of Mental Health, University of California San Diego, University Hospital Carl Gustav Carus, Technische Universität Dresden, The University of Adelaide, Institut Pasteur, Newman University, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Cincinnati, Black Dog Institute, UNSW Sydney, University Medical Center Groningen, University of Groningen, Poznan University of Medical Sciences, University of Tulsa, Dalhousie University, Karolinska University Hospital, University of Gothenburg, University of Exeter, National Institute of Mental Health, Cardiff University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: William K. Warren Foundation, University of Pennsylvania, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Australian Government, Nova Scotia Health Research Foundation, National Institute for Health and Care Research, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Stiftelsen för Strategisk Forskning, Fundação de Amparo à Pesquisa do Estado de São Paulo, ZonMw, Bundesministerium für Bildung und Forschung, Generalitat de Catalunya, Fondation pour la Recherche Médicale, Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya, Dalhousie University, Ministerio de Economía y Competitividad, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Norges Forskningsråd, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, National Center for Mental Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, CHIST-ERA
Awards: Hospital Alerting Via Electronic Noticeboard (HAVEN), G1093531541, G119964413, G1216156242, Quantitative Genetic Analyisis of Brain Structural Phenotypes, Neuroimaging abnormalities in major depressive disorder: effect of inflammation, G195189521, G195474297, G1963378339, Neuroimaging of Dimensional Reward Dysfunction in Adolescence, G2313538783, G2562594150, G2621920312, G2973790809, NIHR Senior Investigator Award, G3154198568, G3218804700, G3277956970, G3433676821, G3615139234, G3728407454, G3781777374, G3926333944, G3934624715, G417657078, Stratifying Resilience and Depression Longitudinally (STRADL), G431279047, Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia, G4404744657, G4594574325, G4616268170, G470506863, G4740033585, G4760961572, G490900884, G5069901229, G5232051750, Trajectory of Brain Structure and Function before and after the Onset of Psychosis: a Longitudinal Multicentre Study, G5710995146, G5779399815, G6085389302, G6105316060, ENIGMA Center for Worldwide Medicine, Imaging & Genomics, G648958512, G6493800209, G6733821374, G6794951016, G7319490576, Longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant, G755819731, G8045000093, G8267165792, G8270261256, G8524812431, G8994360641, G9000052471, G9000073526, G9000074088, G9000204007, G9000210308, G9000335232
OpenAlex ID: W2596902563