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In vivo hippocampal subfield volumes in bipolar disorder—A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

Haukvik, U.K., Gurholt, T.P., Nerland, S., Elvsåshagen, T., Akudjedu, T.N., Alda, M. and ENIGMA Bipolar Disorder Working Group, , 2022. In vivo hippocampal subfield volumes in bipolar disorder—A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group. Human Brain Mapping, 43 (1), 385-398.

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DOI: 10.1002/hbm.25249


The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta‐Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1‐weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed‐effects models and mega‐analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = −0.20), cornu ammonis (CA)1 (d = −0.18), CA2/3 (d = −0.11), CA4 (d = −0.19), molecular layer (d = −0.21), granule cell layer of dentate gyrus (d = −0.21), hippocampal tail (d = −0.10), subiculum (d = −0.15), presubiculum (d = −0.18), and hippocampal amygdala transition area (d = −0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non‐users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Item Type:Article
Additional Information:Funding information: Instituto de Salud Carlos III, FEDER Funds/European Regional Development Fund, Grant/Award Numbers: PI19/00394, CPII19/00009; Departament de Salut de la Generalitat de Catalunya, Grant/Award Number: SLT002/16/00331; FAPESP; Singapore Bioimaging Consortium, Grant/Award Number: RP C‐009/2006; NWO/ZonMW VENI‐Grant, Grant/Award Number: 016.126.059; Netherlands Organization for Health Research and Development (ZonMw), Program Mental Health, Education of Investigators in Mental Health, Grant/Award Number: 100‐002‐034; NIGMS, Grant/Award Number: P20GM121312; NIMH, Grant/Award Number: R21MH113871; William K Warren Foundation; National Research Foundation, South Africa and University Research Committee, University of Cape Town; Wellcome Trust Strategic Award, Grant/Award Number: 104036/Z/14/Z; European Community's Seventh Framework Program, Grant/Award Number: FP7/2007‐2013; Lansdowne Foundation; Australian National Medical and Health Research Council, Grant/Award Numbers: 1063960, 1066177, 1037196; Ebbe Frøland Foundation; Oslo University Hospital—Rikshospitalet; PRISMA UT—Colciencias and Convocatoria Programática Ciencias de la Salud 2014‐2015 by CODI‐Universidad de Antioquia U de A; Interdisciplinary Center for Clinical Research (IZKF) of the Medical Faculty of Münster, Grant/Award Numbers: SEED11/18, Dan3/012/17; German Research Foundation, Grant/Award Numbers: KO 4291/3‐1, NE 2254/1‐2, KR 3822/7‐2, KR 3822/5‐1, KI 588/14‐2, KI 588/14‐1, DA 1151/5‐2, DA 1151/5‐1, FOR2107, SFB‐TRR58; Bipolar Disorder Research Network (BDRN), Grant/Award Number: 17319; Italian Ministry of Health, Grant/Award Numbers: RF‐2011‐02350980, RF‐2016‐02364582; European Regional Development Fund/European Social Fund, Grant/Award Numbers: PI18/00877, PI18/00810, CD18/00029, CD16/00264, MSII16/00018; Instituto de Salud Carlos III; Generalitat de Catalunya, Grant/Award Number: 2017SGR1271; National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship, Grant/Award Numbers: APP1156072, 1059660; AstraZeneca; Brain & Behavior Research Foundation; Dalhousie Clinical Research Scholarship; Nova Scotia Health Research Foundation; Canadian Institutes of Health Research, Grant/Award Numbers: 142255, 106469, 103703; Health Research Board, Grant/Award Number: HRA‐POR‐324; South‐Eastern Norway Regional Health Authority, Grant/Award Numbers: 2014097, 2017112, 2017097; KG Jebsen Stiftelsen; The Research Council of Norway, Grant/Award Numbers: 288083, 250358, 213700, 223273; National Institutes of Health (NIH), Grant/Award Numbers: R01MH116147, U54EB020403, 5T32MH073526, T32AG058507, R01AG059874, R01MH117601, U54 EB020403
Uncontrolled Keywords:bipolar disorder subtype; hippocampus; large‐scale; lithium; psychosis; structural brain MRI
Group:Faculty of Health & Social Sciences
ID Code:34709
Deposited By: Symplectic RT2
Deposited On:20 Oct 2020 09:25
Last Modified:14 Mar 2022 14:24


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