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

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TitleCortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.
Publication TypeJournal Article
Year of Publication2018
AuthorsHibar, DP, Westlye, LT, Doan, NT, Jahanshad, N, Cheung, JW, Ching, CRK, Versace, A, Bilderbeck, AC, Uhlmann, A, Mwangi, B, Krämer, B, Overs, B, Hartberg, CB, Abé, C, Dima, D, Grotegerd, D, Sprooten, E, Bøen, E, Jimenez, E, Howells, FM, Delvecchio, G, Temmingh, H, Starke, J, Almeida, JRC, Goikolea, JM, Houenou, J, Beard, LM, Rauer, L, Abramovic, L, Bonnin, M, Ponteduro, MF, Keil, M, Rive, MM, Yao, N, Yalin, N, Najt, P, Rosa, PG, Redlich, R, Trost, S, Hagenaars, S, Fears, SC, Alonso-Lana, S, van Erp, TGM, Nickson, T, Chaim-Avancini, TM, Meier, TB, Elvsåshagen, T, Haukvik, UK, Lee, WH, Schene, AH, Lloyd, AJ, Young, AH, Nugent, A, Dale, AM, Pfennig, A, McIntosh, AM, Lafer, B, Baune, BT, Ekman, CJ, Zarate, CA, Bearden, CE, Henry, C, Simhandl, C, McDonald, C, Bourne, C, Stein, DJ, Wolf, DH, Cannon, DM, Glahn, DC, Veltman, DJ, Pomarol-Clotet, E, Vieta, E, Canales-Rodriguez, EJ, Nery, FG, Duran, FLS, Busatto, GF, Roberts, G, Pearlson, GD, Goodwin, GM, Kugel, H, Whalley, HC, Ruhe, HG, Soares, JC, Fullerton, JM, Rybakowski, JK, Savitz, J, Chaim, KT, Fatjó-Vilas, M, Soeiro-de-Souza, MG, Boks, MP, Zanetti, MV, Otaduy, MCG, Schaufelberger, MS, Alda, M, Ingvar, M, Phillips, ML, Kempton, MJ, Bauer, M, Landén, M, Lawrence, NS, van Haren, NEM, Horn, NR, Freimer, NB, Gruber, O, Schofield, PR, Mitchell, PB, Kahn, RS, Lenroot, R, Machado-Vieira, R, Ophoff, RA, Sarró, S, Frangou, S, Satterthwaite, TD, Hajek, T, Dannlowski, U, Malt, UF, Arolt, V, Gattaz, WF, Drevets, WC, Caseras, X, Agartz, I, Thompson, PM, Andreassen, OA
JournalMol Psychiatry
Date Published2018 04
KeywordsAdolescent, Adult, Age Factors, Bipolar Disorder, Brain, Case-Control Studies, Cerebral Cortex, Female, Frontal Lobe, Gray Matter, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prefrontal Cortex, Psychotic Disorders, Sex Factors, Temporal Lobe, Young Adult

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.

Alternate JournalMol. Psychiatry
PubMed ID28461699
PubMed Central IDPMC5668195
Grant ListK23 MH074644 / MH / NIMH NIH HHS / United States
P41 EB015922 / EB / NIBIB NIH HHS / United States
K23 MH098130 / MH / NIMH NIH HHS / United States
R01 MH095454 / MH / NIMH NIH HHS / United States
106469 / / CIHR / Canada
R01 MH104284 / MH / NIMH NIH HHS / United States
K08 MH086786 / MH / NIMH NIH HHS / United States
142255 / / CIHR / Canada
P30 NS062691 / NS / NINDS NIH HHS / United States
R01 MH101111 / MH / NIMH NIH HHS / United States
MR/J008915/1 / / Medical Research Council / United Kingdom
U54 EB020403 / EB / NIBIB NIH HHS / United States
103703 / / CIHR / Canada
K01 MH096077 / MH / NIMH NIH HHS / United States
K23 MH085096 / MH / NIMH NIH HHS / United States
R01 MH075007 / MH / NIMH NIH HHS / United States
/ / Wellcome Trust / United Kingdom
64410 / / CIHR / Canada
R01 MH107703 / MH / NIMH NIH HHS / United States
R01 MH085667 / MH / NIMH NIH HHS / United States
R01 MH090553 / MH / NIMH NIH HHS / United States
R01 MH076971 / MH / NIMH NIH HHS / United States