TY - JOUR
T1 - In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics throughMeta-AnalysisBipolar Disorder Working Group
AU - Haukvik, Unn K.
AU - Gurholt, Tiril P.
AU - Nerland, Stener
AU - Elvsashagen, Torbjorn
AU - Akudjedu, Theophilus N.
AU - Alda, Martin
AU - Alnaes, Dag
AU - Alonso-Lana, Silvia
AU - Bauer, Jochen
AU - Baune, Bernhard T.
AU - Benedetti, Francesco
AU - Berk, Michael
AU - Bettella, Francesco
AU - Boen, Erlend
AU - Bonnin, Caterina M.
AU - Brambilla, Paolo
AU - Canales-Rodriguez, Erick J.
AU - Cannon, Dara M.
AU - Caseras, Xavier
AU - Dandash, Orwa
AU - Dannlowski, Udo
AU - Delvecchio, Giuseppe
AU - Diaz-Zuluaga, Ana M.
AU - Erp, Theo G. M.
AU - Fatjo-Vilas, Mar
AU - Foley, Sonya F.
AU - Foerster, Katharina
AU - Fullerton, Janice M.
AU - Goikolea, Jose M.
AU - Grotegerd, Dominik
AU - Gruber, Oliver
AU - Haarman, Bartholomeus C. M.
AU - Haatveit, Beathe
AU - Hajek, Tomas
AU - Hallahan, Brian
AU - Harris, Mathew
AU - Hawkins, Emma L.
AU - Howells, Fleur M.
AU - Huelsmann, Carina
AU - Jahanshad, Neda
AU - Jorgensen, Kjetil N.
AU - Kircher, Tilo
AU - Kraemer, Bernd
AU - Krug, Axel
AU - Kuplicki, Rayus
AU - Lagerberg, Trine
AU - Lancaster, Thomas M.
AU - Lenroot, Rhoshel K.
AU - Lonning, Vera
AU - Meer, Dennis
AU - ENIGMA Bipolar Disorder Working Group
PY - 2022/1
Y1 - 2022/1
N2 - 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'sd = -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.
AB - 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'sd = -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.
KW - bipolar disorder subtype
KW - hippocampus
KW - large-scale
KW - lithium
KW - psychosis
KW - structural brain MRI
KW - LITHIUM-TREATED PATIENTS
KW - CELL-PROLIFERATION
KW - DENTATE GYRUS
KW - SCHIZOPHRENIA
KW - SEGMENTATION
KW - BRAIN
KW - INTERNEURONS
KW - HALOPERIDOL
KW - ATLAS
KW - MRI
U2 - 10.1002/hbm.25249
DO - 10.1002/hbm.25249
M3 - Article
C2 - 33073925
VL - 43
SP - 385
EP - 398
JO - Human Brain Mapping
JF - Human Brain Mapping
SN - 1065-9471
IS - 1
ER -