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

Unn K. Haukvik*, Tiril P. Gurholt*, Stener Nerland, Torbjørn Elvsåshagen, Theophilus N. Akudjedu, Martin Alda, Dag Alnæs, Silvia Alonso-Lana, Jochen Bauer, Bernhard T. Baune, Francesco Benedetti, Michael Berk, Francesco Bettella, Erlend Bøen, Caterina M. Bonnín, Paolo Brambilla, Erick J. Canales-Rodríguez, Dara M. Cannon, Xavier Caseras, Orwa DandashUdo Dannlowski, Giuseppe Delvecchio, Ana M. Díaz-Zuluaga, Theo G. M. van Erp, Mar Fatjó-Vilas, Sonya F. Foley, Katharina Förster, Janice M. Fullerton, José M. Goikolea, Dominik Grotegerd, Oliver Gruber, Bartholomeus C. M. Haarman, Beathe Haatveit, Tomas Hajek, Brian Hallahan, Mathew Harris, Emma L. Hawkins, Fleur M. Howells, Carina Hülsmann, Neda Jahanshad, Kjetil N. Jørgensen, Tilo Kircher, Bernd Krämer, Axel Krug, Rayus Kuplicki, Trine V. Lagerberg, Thomas M. Lancaster, Rhoshel K. Lenroot, Vera Lonning, Carlos López-Jaramillo, Ulrik F. Malt, Colm McDonald, Andrew M. McIntosh, Genevieve McPhilemy, Dennis van der Meer, Ingrid Melle, Elisa M. T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadić, Viola Oertel, Lucio Oldani, Nils Opel, Maria C. G. Otaduy, Bronwyn J. Overs, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Joaquim Radua, Lisa Rauer, Ronny Redlich, Jonathan Repple, Maria M. Rive, Gloria Roberts, Henricus G. Ruhe, Lauren E. Salminen, Raymond Salvador, Salvador Sarró, Jonathan Savitz, Aart H. Schene, Kang Sim, Marcio G. Soeiro-de-Souza, Michael Stäblein, Dan J. Stein, Frederike Stein, Christian K. Tamnes, Henk S. Temmingh, Sophia I. Thomopoulos, Dick J. Veltman, Eduard Vieta, Lena Waltemate, Lars T. Westlye, Heather C. Whalley, Philipp G. Sämann, Paul M. Thompson, Christopher R. K. Ching, Ole A. Andreassen, ENIGMA Bipolar Disorder Working Group, Ingrid Agartz

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
JournalHuman Brain Mapping
Early online date2020
DOIs
Publication statusE-pub ahead of print - 2020

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