In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.
Journal: Human brain mapping
Volume: 43
Issue: 1
Year of Publication: 2022
Affiliated Institutions:
Department of Adult Mental Health, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
FIDMAG Germanes Hospitalàries Research Foundation, CIBERSAM, Barcelona, Spain.
Institute of Clinical Radiology, University of Münster, Münster, Germany.
Department of Psychiatry, University of Münster, Münster, Germany.
Psychiatry and Clinical Psychobiology, Scientific Institute Ospedale San Raffaele, Milan, Italy.
Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Victoria, Australia.
Psychosomatic and CL Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Barcelona Bipolar Disorders and Depressive Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Brain, Mind and Society Research Hub, Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Research Group in Psychiatry, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellín, Antioquia, Colombia.
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, USA.
Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Cardiff, UK.
Neuroscience Research Australia, Randwick, New South Wales, Australia.
Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, Western Cape, South Africa.
Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California, USA.
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
LIM, Department of Radiology and Oncology, University of São Paulo, São Paulo, Brazil.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona, Spain.
Psychiatry, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.
Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
West Region/Institute of Mental Health, Singapore, Singapore.
Department of Psychiatry, Universidade de São Paulo, São Paulo, Brazil.
Department of Psychiatry, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Max Planck Institute of Psychiatry, Munich, Germany.
Abstract summary
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.
Authors & Co-authors:
Haukvik Unn K UK
Gurholt Tiril P TP
Nerland Stener S
Elvsåshagen Torbjørn T
Akudjedu Theophilus N TN
Alda Martin M
Alnaes Dag D
Alonso-Lana Silvia S
Bauer Jochen J
Baune Bernhard T BT
Benedetti Francesco F
Berk Michael M
Bettella Francesco F
Bøen Erlend E
Bonnín Caterina M CM
Brambilla Paolo P
Canales-Rodríguez Erick J EJ
Cannon Dara M DM
Caseras Xavier X
Dandash Orwa O
Dannlowski Udo U
Delvecchio Giuseppe G
Díaz-Zuluaga Ana M AM
van Erp Theo G M TGM
Fatjó-Vilas Mar M
Foley Sonya F SF
Förster Katharina K
Fullerton Janice M JM
Goikolea José M JM
Grotegerd Dominik D
Gruber Oliver O
Haarman Bartholomeus C M BCM
Haatveit Beathe B
Hajek Tomas T
Hallahan Brian B
Harris Mathew M
Hawkins Emma L EL
Howells Fleur M FM
Hülsmann Carina C
Jahanshad Neda N
Jørgensen Kjetil N KN
Kircher Tilo T
Krämer Bernd B
Krug Axel A
Kuplicki Rayus R
Lagerberg Trine V TV
Lancaster Thomas M TM
Lenroot Rhoshel K RK
Lonning Vera V
López-Jaramillo Carlos C
Malt Ulrik F UF
McDonald Colm C
McIntosh Andrew M AM
McPhilemy Genevieve G
van der Meer Dennis D
Melle Ingrid I
Melloni Elisa M T EMT
Mitchell Philip B PB
Nabulsi Leila L
Nenadić Igor I
Oertel Viola V
Oldani Lucio L
Opel Nils N
Otaduy Maria C G MCG
Overs Bronwyn J BJ
Pineda-Zapata Julian A JA
Pomarol-Clotet Edith E
Radua Joaquim J
Rauer Lisa L
Redlich Ronny R
Repple Jonathan J
Rive Maria M MM
Roberts Gloria G
Ruhe Henricus G HG
Salminen Lauren E LE
Salvador Raymond R
Sarró Salvador S
Savitz Jonathan J
Schene Aart H AH
Sim Kang K
Soeiro-de-Souza Marcio G MG
Stäblein Michael M
Stein Dan J DJ
Stein Frederike F
Tamnes Christian K CK
Temmingh Henk S HS
Thomopoulos Sophia I SI
Veltman Dick J DJ
Vieta Eduard E
Waltemate Lena L
Westlye Lars T LT
Whalley Heather C HC
Sämann Philipp G PG
Thompson Paul M PM
Ching Christopher R K CRK
Andreassen Ole A OA
Agartz Ingrid I
Study Outcome
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