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Subcortical volumetric abnormalities in bipolar disorder

Lookup NU author(s): Dr Adrian Lloyd



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d= -0.232; P = 3.50 x 10(-7)) and thalamus (d= -0.148; P = 4.27 x 10(-3)) and enlarged lateral ventricles (d= -0.260; P = 3.93 x 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Publication metadata

Author(s): Hibar DP, Westlye LT, van Erp TGM, Rasmussen J, Leonardo CD, Faskowitz J, Haukvik UK, Hartberg CB, Doan NT, Agartz I, Dale AM, Gruber O, Kramer B, Trost S, Liberg B, Abe C, Ekman CJ, Ingvar M, Landen M, Fears SC, Freimer NB, Bearden CE, Sprooten E, Glahn DC, Pearlson GD, Emsell L, Kenney J, Scanlon C, McDonald C, Cannon DM, Almeida J, Versace A, Caseras X, Lawrence NS, Phillips ML, Dima D, Delvecchio G, Frangou S, Satterthwaite TD, Wolf D, Houenou J, Henry C, Malt UF, Boen E, Elvsashagen T, Young AH, Lloyd AJ, Goodwin GM, Mackay CE, Bourne C, Bilderbeck A, Abramovic L, Boks MP, van Haren NEM, Ophoff RA, Kahn RS, Bauer M, Pfennig A, Alda M, Hajek T, Mwangi B, Soares JC, Nickson T, Dimitrova R, Sussmann JE, Hagenaars S, Whalley HC, McIntosh AM, Thompson PM, Andreassen OA, Costa Rica Colombia Consortium Gen, ENIGMA Bipolar Disorder Working Gr

Publication type: Article

Publication status: Published

Journal: Molecular Psychiatry

Year: 2016

Volume: 21

Issue: 12

Pages: 1710-1716

Print publication date: 01/12/2016

Online publication date: 09/02/2016

Acceptance date: 11/12/2015

Date deposited: 20/01/2017

ISSN (print): 1359-4184

ISSN (electronic): 1476-5578

Publisher: Nature Publishing Group


DOI: 10.1038/mp.2015.227


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Funder referenceFunder name
Joanne and George Miller Family Endowed Term Chair
Kristian Gerhard Jebsen Foundation
National Centre for Mental Health (NCMH)
South East Norway Health Authority
Swedish Federal Government under the LUA/ALF
Bipolar Disorder Research Network (BDRN)
Brain Behavior Research Foundation
Fondamental Foundation
French National Agency for Research (MNP)
Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship
Research Council of Norway
Swedish Brain foundation
Swedish foundation for Strategic Research
Swedish Medical Research Council
106469Canadian Institutes of Health Research
103703Canadian Institutes of Health Research
64410Canadian Institutes of Health Research
602450European Community
U54 EB020403NIH
R01 MH090553NIMH