White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Lorielle M F Dietze^{1

2}, Sean R McWhinney², Pauline Favre^{3

4}, Christoph Abé^{5

6}, Nina Alexander⁷, Carlotta Barkhau⁸, Francesco Benedetti^{9

10}, Michael Berk¹¹, Erlend Bøen¹², Birgitte Boye^{12

13}, Katharina Brosch⁷, Erick J Canales-Rodríguez^{14

15}, Dara M Cannon¹⁶, Sean P Carruthers¹⁷, Emily L V Corkum², Udo Dannlowski⁸, Ana M Díaz-Zuluaga¹⁸, Katharina Dohm⁸, Torbjørn Elvsåshagen^{13

19

20}, Kira Flinkenflügel⁸, Lydia Fortea²¹, Lisa S Furlong²², Benjamin I Goldstein²³, Dominik Grotegerd⁸, Marius Gruber^{8

24}, Bartholomeus C M Haarman²⁵, Fleur M Howells^{26

27}, Neda Jahanshad²⁸, Hamidreza Jamalabadi⁷, Andreas Jansen^{7

29}, James A Karantonis²², Kody G Kennedy²³, Tilo T J Kircher⁷, Anna Luisa Klahn³⁰, Peter Kochunov³¹, Anna Kraus⁸, Mikael Landén^{30

32}, Carlos López-Jaramillo¹⁸, Bradley J MacIntosh^{23

33

34}, Elena Mazza^{9

10}, Colm McDonald¹⁶, Andrew M McIntosh^{35

36}, Hannah Meinert⁸, Susanne Meinert^{8

37}, Elisa M T Melloni^{9

10}, Philip B Mitchell^{38

39}, Igor Nenadić⁷, Nils Opel^{8

40

41}, Mary Phillips⁴², Camille Piguet⁴³, Mircea Polosan⁴⁴, Edith Pomarol-Clotet^{14

15}, Arnaud Pouchon⁴⁴, Joaquim Radua^{15

21}, Gloria Roberts³⁸, Alex J Ross², Susan L Rossell^{17

45}, Raymond Salvador^{14

15}, Kang Sim^{46

47

48}, Jair C Soares³¹, Giovana B Zunta-Soares³¹, Frederike Stein⁷, Benjamin Straube⁷, Chao Suo¹¹, Lea Teutenberg⁷, Florian Thomas-Odenthal⁷, Sophia I Thomopoulos²⁸, Paula Usemann⁷, Tamsyn E Van Rheenen^{17

22}, Amelia Versace⁴², Eduard Vieta^{15

21

49}, Enric Vilajosana^{15

21}, Benson Mwangi³¹, Wei Wen³⁸, Heather C Whalley^{35

36}, Mon-Ju Wu³¹, Ole A Andreassen^{50

51}, Christopher R K Ching²⁸, Paul M Thompson²⁸, Josselin Houenou^{3

4

52

53}, Tomas Hajek^{54

55}; ENIGMA Bipolar Disorder Working Group; ENIGMA BMI-X Working Group

Collaborators, Affiliations

Collaborators

Edith Pomarol-Clotet, Tamsyn E Van Rheenen

Affiliations

¹ Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
² Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
³ Neurospin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
⁴ INSERM Unit U955, Team Translational Neuropsychiatry, Créteil, France.
⁵ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Quantify Research Stockholm Sweden, Stockholm, Sweden.
⁷ Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Marburg, Germany.
⁸ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁹ Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
¹⁰ University Vita-Salute San Raffaele, Milano, Italy.
¹¹ Institute for Mental and Physical Health and Clinical Translation School of Medicine, Deakin University, Geelong, VIC, Australia.
¹² Unit for Psychosomatics and C-L psychiatry for adults, Oslo University Hospital, Oslo, Norway.
¹³ Department of Behavioural Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
¹⁴ FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
¹⁵ Mental Health Research Networking Center (CIBERSAM), ISC III, Barcelona, Spain.
¹⁶ Centre for Neuroimaging and Cognitive Genomics, Clinical Neuroimaging Laboratory, Galway Neuroscience Centre, College of Medicine, Nursing, and Health Sciences, University of Galway, Galway, Ireland.
¹⁷ Centre for Mental Health and Brain Sciences, School of Health Sciences, Swinburne University, Melbourne, VIC, Australia.
¹⁸ Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia.
¹⁹ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²⁰ Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
²¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
²² Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
²³ Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
²⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Goethe, Germany.
²⁵ Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁶ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
²⁷ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
²⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
²⁹ Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany.
³⁰ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
³¹ Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
³² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³³ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
³⁴ Center for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
³⁵ Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK.
³⁶ Generation Scotland, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³⁷ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
³⁸ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
³⁹ Black Dog Institute, Sydney, Sydney, NSW, Australia.
⁴⁰ Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany.
⁴¹ German Center for Mental Health (DZPG), Jena, Germany.
⁴² University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁴³ Synapsy Center, Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁴⁴ Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France.
⁴⁵ Department of Psychiatry, St. Vincent's Hospital, Melbourne, Australia.
⁴⁶ West Region, Institute of Mental Health, Singapore, Singapore.
⁴⁷ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁴⁸ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁴⁹ Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clínic, Barcelona, Spain.
⁵⁰ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁵¹ NORMENT Centre, University of Oslo, Oslo, Norway.
⁵² Assistance Publique-Hôpitaux de Paris (AP-HP), CHU Mondor, Psychiatry Department, Créteil, France.
⁵³ Faculté de Médecine, Université Paris Est Créteil, Créteil, France.
⁵⁴ Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. tomas.hajek@dal.ca.
⁵⁵ National Institute of Mental Health, Klecany, Czech Republic. tomas.hajek@dal.ca.

PMID: 39501059
DOI: 10.1038/s41380-024-02784-2

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Lorielle M F Dietze et al. Mol Psychiatry. 2025 May.

. 2025 May;30(5):1770-1779.

doi: 10.1038/s41380-024-02784-2. Epub 2024 Nov 5.

Authors

Collaborators

Edith Pomarol-Clotet, Tamsyn E Van Rheenen

Affiliations

¹ Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
² Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
³ Neurospin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
⁴ INSERM Unit U955, Team Translational Neuropsychiatry, Créteil, France.
⁵ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁶ Quantify Research Stockholm Sweden, Stockholm, Sweden.
⁷ Department of Psychiatry and Psychotherapy, Philipps-Universität Marburg, Marburg, Germany.
⁸ Institute for Translational Psychiatry, University of Münster, Münster, Germany.
⁹ Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
¹⁰ University Vita-Salute San Raffaele, Milano, Italy.
¹¹ Institute for Mental and Physical Health and Clinical Translation School of Medicine, Deakin University, Geelong, VIC, Australia.
¹² Unit for Psychosomatics and C-L psychiatry for adults, Oslo University Hospital, Oslo, Norway.
¹³ Department of Behavioural Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
¹⁴ FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.
¹⁵ Mental Health Research Networking Center (CIBERSAM), ISC III, Barcelona, Spain.
¹⁶ Centre for Neuroimaging and Cognitive Genomics, Clinical Neuroimaging Laboratory, Galway Neuroscience Centre, College of Medicine, Nursing, and Health Sciences, University of Galway, Galway, Ireland.
¹⁷ Centre for Mental Health and Brain Sciences, School of Health Sciences, Swinburne University, Melbourne, VIC, Australia.
¹⁸ Research Group in Psychiatry GIPSI, Department of Psychiatry, Faculty of Medicine, Universidad de Antioquia, Medellin, Colombia.
¹⁹ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²⁰ Department of Neurology, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
²¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
²² Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia.
²³ Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
²⁴ Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Goethe, Germany.
²⁵ Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁶ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
²⁷ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
²⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
²⁹ Core-Facility Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany.
³⁰ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
³¹ Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
³² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
³³ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
³⁴ Center for Brain Resilience & Recovery, Hurvitz Brain Sciences Program, Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
³⁵ Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK.
³⁶ Generation Scotland, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³⁷ Institute for Translational Neuroscience, University of Münster, Münster, Germany.
³⁸ Discipline of Psychiatry and Mental Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia.
³⁹ Black Dog Institute, Sydney, Sydney, NSW, Australia.
⁴⁰ Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany.
⁴¹ German Center for Mental Health (DZPG), Jena, Germany.
⁴² University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁴³ Synapsy Center, Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
⁴⁴ Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France.
⁴⁵ Department of Psychiatry, St. Vincent's Hospital, Melbourne, Australia.
⁴⁶ West Region, Institute of Mental Health, Singapore, Singapore.
⁴⁷ Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁴⁸ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
⁴⁹ Bipolar Disorders Unit, Clinical Institute of Neurosciences, Hospital Clínic, Barcelona, Spain.
⁵⁰ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁵¹ NORMENT Centre, University of Oslo, Oslo, Norway.
⁵² Assistance Publique-Hôpitaux de Paris (AP-HP), CHU Mondor, Psychiatry Department, Créteil, France.
⁵³ Faculté de Médecine, Université Paris Est Créteil, Créteil, France.
⁵⁴ Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. tomas.hajek@dal.ca.
⁵⁵ National Institute of Mental Health, Klecany, Czech Republic. tomas.hajek@dal.ca.

PMID: 39501059
DOI: 10.1038/s41380-024-02784-2

Abstract

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.

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Conflict of interest statement

Competing interests: PMT, CRKC and NJ received past research support from Biogen Inc. for work unrelated to this manuscript. TE is a consultant to Sumitomo Pharma and Cumulus and received speaker’s honoraria from Lundbeck and Janssen Cilag. Texas cohort (JS) has received speaking/consulting and/or research grants from: ALKERMES (Advisory Board), BOEHRINGER Ingelheim (Consultant), COMPASS Pathways (Research Grant), JOHNSON & JOHNSON (Consultant), LIVANOVA (Consultant), RELMADA (Research Grant), SUNOVION (Research Grant), Mind Med (Research Grant).

References

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White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Collaborators

Affiliations

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources