Evidence map›Paper›PMID 42092437›Full record

ArticleBiological psychiatry2026

Structural Brain Network Alterations in Relation to Treatment and Illness Severity in Bipolar Disorder.

Leila Nabulsi, Melody J Y Kang, Neda Jahanshad, Genevieve McPhilemy, Fiona M Martyn, Bartholomeus Haarman, Colm McDonald, Brian Hallahan, Stefani O'Donoghue, Dan J Stein and 48 more

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Article in Biological psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

58 authors.

Leila NabulsiImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California; Clinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland. Electronic address: lnabulsi@usc.edu.
Melody J Y KangImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.
Genevieve McPhilemyClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Fiona M MartynClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Bartholomeus HaarmanDepartment of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Colm McDonaldClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Brian HallahanClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Stefani O'DonoghueClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
Dan J SteinNeuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
Fleur M HowellsDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Freda SchefflerNeuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Henk S TemminghDepartment of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
David C GlahnDepartment of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Amanda RodrigueDepartment of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Edith Pomarol-ClotetBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Eduard VietaBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Barcelona Bipolar Disorders and Depressive Unit, Hospital Clínic, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
Joaquim RaduaBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; Barcelona Bipolar Disorders and Depressive Unit, Hospital Clínic, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
Raymond SalvadorBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Andriana KarukBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
Erick J Canales-RodríguezBiomedical Research Networking Center for Mental Health Network, Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain; Signal Processing Laboratory, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Josselin HouenouNorthern Health, Mental Health Division, and the University of Melbourne, Melbourne, Victoria, Australia.
Pauline FavreInstitut National de la Santé et de la Recherche Médicale U955, team "Translational Neuro-Psychiatry," Créteil, France; Neurospin, CEA Paris-Saclay, team "Translational and Applicative Neuroimaging Research Unit," Gif-sur-Yvette, France.
Mircea PolosanUniversity Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; Institut National de la Santé et de la Recherche Médicale U1216, Grenoble Institut des Neurosciences, La Tronche, France.
Arnaud PouchonUniversity Grenoble Alpes, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; Institut National de la Santé et de la Recherche Médicale U1216, Grenoble Institut des Neurosciences, La Tronche, France.
Paolo BrambillaDepartment of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Department of Neurosciences and Mental Health, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Marcella BellaniSection of Psychiatry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Philip B MitchellDiscipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Gloria RobertsDiscipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Udo DannlowskiInstitute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Protestant Hospital of the Bethel Foundation, Medical School and University Medical Center OWL, Bielefeld University, Bielefeld, Germany.
Tiana BorgersInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Susanne MeinertInstitute for Translational Psychiatry, University of Münster, Münster, Germany; Institute for Translational Neuroscience, University of Münster, Münster, Germany.
Kira FlinkenflügelInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Jonathan ReppleInstitute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt, Germany; Cooperative Brain Imaging Center, Goethe University Frankfurt, Frankfurt, Germany.
Elisabeth J LeehrInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Dominik GrotegerdInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Tim HahnInstitute for Translational Psychiatry, University of Münster, Münster, Germany.
Michèle WessaCentral Institute of Mental Health, Department of Neuropsychology and Psychological Resilience Research, Mannheim, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Department of Cancer Survivorship and Psychological Resilience, German Cancer Research Center Heidelberg, Heidelberg, Germany.
Mary L PhillipsDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
Lea TeutenbergDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Tilo KircherDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Benjamin StraubeDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Olaf SteinstraeterDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Frederike SteinDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Florian Thomas-OdenthalDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Nina AlexanderDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Paula L UsemannDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany.
Andreas JansenDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Philipps-Universität Marburg, Marburg, Germany; Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany.
Michael BerkOrygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia; Centre for Youth Mental Health, University of Melbourne, Parkville, Victoria, Australia; IMPACT Institute, School of Medicine, Deakin University, Geelong, Victoria, Australia; Orygen Youth Health Clinical Program, Parkville, Victoria, Australia; Barwon Health and the Geelong Clinic, Geelong, Victoria, Australia.
Orwa DandashBrain and Mental Health Laboratory, School of Psychological Science and Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, Victoria, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, Victoria, Australia.
Nadine ParkerCentre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Chao SuoTurner Institute for Brain and Mental Health, School of Psychological Science and Monash Biomedical Imaging, Monash University, Victoria, Australia; Queensland Institute of Medical Research Berghofer, Berghofer, Queensland, Australia; Healthy Brain and Mind Research Centre, School of Behavioral and Health Sciences, Faculty of Health Sciences, Australian Catholic University, Fitzroy, Victoria, Australia; School of Psychology, University of Queensland, Brisbane, Queensland, Australia.
Sophia I ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.
Ole A AndreassenCentre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Christopher R K ChingImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, University of Southern California, Marina del Rey, California.
Dara M CannonClinical Neuroimaging Laboratory, Centre for Neuroimaging, Cognition and Genomics, Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, University of Galway, Galway, Ireland.
ENIGMA Bipolar Disorder Working Group

Funding

Bipolar & Schizophrenia Consortium for Parsing Intermediate PhenotypesR01MH077945 · NIMH · YALE UNIVERSITY · PI PEARLSON, GODFREY D · 2007 to 2019
$7.6M
Gene Networks Influencing Psychotic Dysconnectivity in African AmericansR01MH106324 · NIMH · YALE UNIVERSITY · PI BLANGERO, JOHN, GLAHN, DAVID C · 2015 to 2019
$4.2M
ENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical OutcomesR01MH129742 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christopher Ching, PAUL M THOMPSON · 2022 to 2026
$3.0M
Influence of Psychosis on Brain-Behavior Endophenotypes for Bipolar DisorderR01MH080912 · NIMH · YALE UNIVERSITY · PI GLAHN, DAVID C · 2008 to 2012
$2.6M
Global studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-ConsortiumR01MH134004 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Neda Jahanshad · 2023 to 2026
$2.6M
NIMH NIH HHS R01 MH077945NIMH NIH HHS R01 MH080912NIMH NIH HHS R01 MH106324NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH134004Wellcome Trust
6 · The paper itself

Abstract

backgroundLarge-scale T1-weighted magnetic resonance imaging (MRI) studies have established gray matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white matter pathways, but prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretical metrics.

methodsCross-sectional structural and diffusion MRI scans from 450 individuals with BD (mean ± SD = 35.7 ± 12.6 years) and 509 control participants (33.3 ± 12.6 years), ages 18 to 65 years, were analyzed across 16 ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD sites. Standardized segmentation/parcellation and constrained spherical deconvolution tractography generated individual structural connectivity matrices. Graph-theoretical metrics of global and subnetwork organization were related to symptom severity and medications.

resultsBD showed widespread network alterations (lower density and efficiency, longer path length, and higher betweenness centrality), altered microstructural organization in a limbic-basal ganglia circuit, and abnormal streamline counts in a default mode/salience/frontolimbic-basal ganglia network. Longer illness duration, later onset, and psychosis history were associated with greater abnormalities in network architecture, whereas more manic episodes were associated with greater frontolimbic connectivity. Antidepressant (particularly selective serotonin reuptake inhibitor), anticonvulsant, and antipsychotic use related to poorer global and frontolimbic connectivity; no clear lithium effects emerged.

conclusionsAs the largest structural connectivity study in BD, we revealed widespread disruption in reward and emotion-regulation networks influenced by illness severity and medication use. Results show that multisite harmonization is feasible and highlight ENIGMA-BD as a scalable framework for identifying reproducible neurobiological markers.

Indexed as

Bipolar disorderDiffusion-weighted imagingGraph theoryIllness severityStructural connectivityTreatment

Identifiers

PMID42092437
PMCPMC13349404

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