In vivo hippocampal subfield volumes in bipolar disorder—A mega‐analysis from The Enhancing Neuro Imaging Genetics through Meta‐Analysis Bipolar Disorder Working Group
Authors: Haukvik Unn K. , Gurholt Tiril P. , Nerland Stener , Elvsåshagen Torbjørn , Akudjedu Theophilus N. , Alda Martin , Alnæs Dag , Alonso‐Lana Silvia , Bauer Jochen , Baune Bernhard T. , Benedetti Francesco , Berk Michael , Bettella Francesco , Bøen Erlend , Bonnín Caterina M. , Brambilla Paolo , Canales‐Rodríguez Erick J. , Cannon Dara M. , Caseras Xavier , Dandash Orwa , Dannlowski Udo , Delvecchio Giuseppe , Díaz‐Zuluaga Ana M. , van Erp Theo G. M. , Fatjó‐Vilas Mar , Foley Sonya F. , Förster Katharina , Fullerton Janice M. , Goikolea José M. , Grotegerd Dominik , Gruber Oliver , Haarman Bartholomeus C. M. , Haatveit Beathe , Hajek Tomas , Hallahan Brian , Harris Mathew , Hawkins Emma L. , Howells Fleur M. , Hülsmann Carina , Jahanshad Neda , Jørgensen Kjetil N. , Kircher Tilo , Krämer Bernd , Krug Axel , Kuplicki Rayus , Lagerberg Trine V. , Lancaster Thomas M. , Lenroot Rhoshel K. , Lonning Vera , López‐Jaramillo Carlos , Malt Ulrik F. , McDonald Colm , McIntosh Andrew M. , McPhilemy Genevieve , van der Meer Dennis , Melle Ingrid , Melloni Elisa M. T. , Mitchell Philip B. , Nabulsi Leila , Nenadić Igor , Oertel Viola , Oldani Lucio , Opel Nils , Otaduy Maria C. G. , Overs Bronwyn J. , Pineda‐Zapata Julian A. , Pomarol‐Clotet Edith , Radua Joaquim , Rauer Lisa , Redlich Ronny , Repple Jonathan , Rive Maria M. , Roberts Gloria , Ruhe Henricus G. , Salminen Lauren E. , Salvador Raymond , Sarró Salvador , Savitz Jonathan , Schene Aart H. , Sim Kang , Soeiro‐de‐Souza Marcio G. , Stäblein Michael , Stein Dan J. , Stein Frederike , Tamnes Christian K. , Temmingh Henk S. , Thomopoulos Sophia I. , Veltman Dick J. , Vieta Eduard , Waltemate Lena , Westlye Lars T. , Whalley Heather C. , Sämann Philipp G. , Thompson Paul M. , Ching Christopher R. K. , Andreassen Ole A. , Agartz Ingrid ,   ENIGMA Bipolar Disorder Working Group
Published: October 2020

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.