Translational Psychiatry (Feb 2024)
Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
- Anna H. Ou,
- Sara B. Rosenthal,
- Mazda Adli,
- Kazufumi Akiyama,
- Nirmala Akula,
- Martin Alda,
- Azmeraw T. Amare,
- Raffaella Ardau,
- Bárbara Arias,
- Jean-Michel Aubry,
- Lena Backlund,
- Michael Bauer,
- Bernhard T. Baune,
- Frank Bellivier,
- Antonio Benabarre,
- Susanne Bengesser,
- Abesh Kumar Bhattacharjee,
- Joanna M. Biernacka,
- Pablo Cervantes,
- Guo-Bo Chen,
- Hsi-Chung Chen,
- Caterina Chillotti,
- Sven Cichon,
- Scott R. Clark,
- Francesc Colom,
- David A. Cousins,
- Cristiana Cruceanu,
- Piotr M. Czerski,
- Clarissa R. Dantas,
- Alexandre Dayer,
- Maria Del Zompo,
- Franziska Degenhardt,
- J. Raymond DePaulo,
- Bruno Étain,
- Peter Falkai,
- Frederike Tabea Fellendorf,
- Ewa Ferensztajn-Rochowiak,
- Andreas J. Forstner,
- Louise Frisén,
- Mark A. Frye,
- Janice M. Fullerton,
- Sébastien Gard,
- Julie S. Garnham,
- Fernando S. Goes,
- Maria Grigoroiu-Serbanescu,
- Paul Grof,
- Oliver Gruber,
- Ryota Hashimoto,
- Joanna Hauser,
- Urs Heilbronner,
- Stefan Herms,
- Per Hoffmann,
- Andrea Hofmann,
- Liping Hou,
- Stephane Jamain,
- Esther Jiménez,
- Jean-Pierre Kahn,
- Layla Kassem,
- Tadafumi Kato,
- Sarah Kittel-Schneider,
- Barbara König,
- Po-Hsiu Kuo,
- Ichiro Kusumi,
- Nina Lackner,
- Gonzalo Laje,
- Mikael Landén,
- Catharina Lavebratt,
- Marion Leboyer,
- Susan G. Leckband,
- Carlos A. López Jaramillo,
- Glenda MacQueen,
- Mario Maj,
- Mirko Manchia,
- Cynthia Marie-Claire,
- Lina Martinsson,
- Manuel Mattheisen,
- Michael J. McCarthy,
- Susan L. McElroy,
- Francis J. McMahon,
- Philip B. Mitchell,
- Marina Mitjans,
- Francis M. Mondimore,
- Palmiero Monteleone,
- Caroline M. Nievergelt,
- Markus M. Nöthen,
- Tomas Novák,
- Urban Ösby,
- Norio Ozaki,
- Sergi Papiol,
- Roy H. Perlis,
- Claudia Pisanu,
- James B. Potash,
- Andrea Pfennig,
- Daniela Reich-Erkelenz,
- Andreas Reif,
- Eva Z. Reininghaus,
- Marcella Rietschel,
- Guy A. Rouleau,
- Janusz K. Rybakowski,
- Martin Schalling,
- Peter R. Schofield,
- K. Oliver Schubert,
- Thomas G. Schulze,
- Barbara W. Schweizer,
- Florian Seemüller,
- Giovanni Severino,
- Tatyana Shekhtman,
- Paul D. Shilling,
- Kazutaka Shimoda,
- Christian Simhandl,
- Claire M. Slaney,
- Alessio Squassina,
- Thomas Stamm,
- Pavla Stopkova,
- Sarah K. Tighe,
- Alfonso Tortorella,
- Gustavo Turecki,
- Eduard Vieta,
- Julia Volkert,
- Stephanie Witt,
- Naomi R. Wray,
- Adam Wright,
- L. Trevor Young,
- Peter P. Zandi,
- John R. Kelsoe
Affiliations
- Anna H. Ou
- Department of Psychiatry, University of California San Diego
- Sara B. Rosenthal
- Center for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego
- Mazda Adli
- Department of Psychiatry and Psychotherapy, Charité— Universitätsmedizin Berlin, Campus Charité Mitte
- Kazufumi Akiyama
- Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine
- Nirmala Akula
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Martin Alda
- Department of Psychiatry, Dalhousie University
- Azmeraw T. Amare
- Discipline of Psychiatry, University of Adelaide
- Raffaella Ardau
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari
- Bárbara Arias
- Department of Evolutive Biology, Ecology and Environmental Sciences, Facultat de Biologia and Institut de Biomedicina (IBUB), Universitat de Barcelona
- Jean-Michel Aubry
- Department of Mental Health and Psychiatry, Mood Disorders Unit—Geneva University Hospitals
- Lena Backlund
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital
- Michael Bauer
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden
- Bernhard T. Baune
- Discipline of Psychiatry, University of Adelaide
- Frank Bellivier
- INSERM UMR-S 1144—Université Paris Cité Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Lariboisière-F Widal
- Antonio Benabarre
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII
- Susanne Bengesser
- Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz
- Abesh Kumar Bhattacharjee
- Department of Psychiatry, University of California San Diego
- Joanna M. Biernacka
- Department of Health Sciences Research, Mayo Clinic
- Pablo Cervantes
- The Neuromodulation Unit, McGill University Health Centre
- Guo-Bo Chen
- The Neuromodulation Unit, McGill University Health Centre
- Hsi-Chung Chen
- Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital
- Caterina Chillotti
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari
- Sven Cichon
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Scott R. Clark
- Discipline of Psychiatry, University of Adelaide
- Francesc Colom
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII
- David A. Cousins
- Campus for Ageing and Vitality, Newcastle University
- Cristiana Cruceanu
- Douglas Mental Health University Institute, McGill University
- Piotr M. Czerski
- Psychiatric Genetic Unit, Poznan University of Medical Sciences
- Clarissa R. Dantas
- Department of Psychiatry, University of Campinas (Unicamp)
- Alexandre Dayer
- Department of Mental Health and Psychiatry, Mood Disorders Unit—Geneva University Hospitals
- Maria Del Zompo
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari
- Franziska Degenhardt
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- J. Raymond DePaulo
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Bruno Étain
- INSERM UMR-S 1144—Université Paris Cité Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Lariboisière-F Widal
- Peter Falkai
- Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich
- Frederike Tabea Fellendorf
- Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz
- Ewa Ferensztajn-Rochowiak
- Department of Adult Psychiatry, Poznan University of Medical Sciences
- Andreas J. Forstner
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Louise Frisén
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital
- Mark A. Frye
- Department of Psychiatry and Psychology, Mayo Clinic
- Janice M. Fullerton
- Mental Illness Research Theme, Neuroscience Research Australia
- Sébastien Gard
- Pôle de Psychiatrie Générale Universitaire, Centre Hospitalier Charles Perrens
- Julie S. Garnham
- Department of Psychiatry, Dalhousie University
- Fernando S. Goes
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Maria Grigoroiu-Serbanescu
- Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital
- Paul Grof
- Mood Disorders Center of Ottawa
- Oliver Gruber
- Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August University Göttingen
- Ryota Hashimoto
- Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry
- Joanna Hauser
- Psychiatric Genetic Unit, Poznan University of Medical Sciences
- Urs Heilbronner
- Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich
- Stefan Herms
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Per Hoffmann
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Andrea Hofmann
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Liping Hou
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Stephane Jamain
- Inserm U955, Psychiatrie Translationnelle
- Esther Jiménez
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII
- Jean-Pierre Kahn
- Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy-Laxou—Université de Lorraine
- Layla Kassem
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Tadafumi Kato
- Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute
- Sarah Kittel-Schneider
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt—Goethe University
- Barbara König
- Department of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen
- Po-Hsiu Kuo
- Institute of Epidemiology and Preventive Medicine, National Taiwan University
- Ichiro Kusumi
- Department of Psychiatry, Hokkaido University Graduate School of Medicine
- Nina Lackner
- Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz
- Gonzalo Laje
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Mikael Landén
- Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the Gothenburg University
- Catharina Lavebratt
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital
- Marion Leboyer
- Assistance Publique-Hôpitaux de Paris, Hôpital Albert Chenevier—Henri Mondor, Pôle de Psychiatrie
- Susan G. Leckband
- Department of Pharmacy, VA San Diego Healthcare System
- Carlos A. López Jaramillo
- Department of Psychiatry, University of Antioquia, Medellín
- Glenda MacQueen
- Department of Psychiatry, University of Calgary
- Mario Maj
- Department of Psychiatry, University of Naples SUN
- Mirko Manchia
- Department of Medical Sciences and Public Health, University of Cagliari
- Cynthia Marie-Claire
- INSERM UMR-S 1144—Université Paris Cité Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Lariboisière-F Widal
- Lina Martinsson
- Department of Clinical Neurosciences, Karolinska Institutet
- Manuel Mattheisen
- Department of Biomedicine, Aarhus University
- Michael J. McCarthy
- Department of Psychiatry, VA San Diego Healthcare System
- Susan L. McElroy
- Department of Psychiatry, Lindner Center of Hope, University of Cincinnati
- Francis J. McMahon
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Philip B. Mitchell
- School of Psychiatry, University of New South Wales, and Black Dog Institute
- Marina Mitjans
- Department of Genetics, Microbiology, and Statistics, Faculty of Biology and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, CIBER de Salud Mental, ISCIII
- Francis M. Mondimore
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Palmiero Monteleone
- Neurosciences Section, Department of Medicine and Surgery, University of Salerno
- Caroline M. Nievergelt
- Department of Psychiatry, University of California San Diego
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center
- Tomas Novák
- National Institute of Mental Health
- Urban Ösby
- Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital
- Norio Ozaki
- Department of Psychiatry, Nagoya University Graduate School of Medicine
- Sergi Papiol
- Ludwig-Maximilians-University of Munich
- Roy H. Perlis
- Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School
- Claudia Pisanu
- Department of Biomedical Sciences, University of Cagliari
- James B. Potash
- Department of Psychiatry, University of Iowa
- Andrea Pfennig
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden
- Daniela Reich-Erkelenz
- Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich
- Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt—Goethe University
- Eva Z. Reininghaus
- Neurobiological Background and Anthropometrics in Bipolar Affective Disorder, Division of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz
- Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Guy A. Rouleau
- Montreal Neurological Institute and Hospital, McGill University
- Janusz K. Rybakowski
- Department of Adult Psychiatry, Poznan University of Medical Sciences
- Martin Schalling
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital
- Peter R. Schofield
- Mental Illness Research Theme, Neuroscience Research Australia
- K. Oliver Schubert
- Discipline of Psychiatry, University of Adelaide
- Thomas G. Schulze
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Barbara W. Schweizer
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Florian Seemüller
- Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich
- Giovanni Severino
- Department of Biomedical Sciences, University of Cagliari
- Tatyana Shekhtman
- Department of Psychiatry, University of California San Diego
- Paul D. Shilling
- Department of Psychiatry, University of California San Diego
- Kazutaka Shimoda
- Department of Psychiatry, Dokkyo Medical University School of Medicine
- Christian Simhandl
- Bipolar Center
- Claire M. Slaney
- Department of Psychiatry, Dalhousie University
- Alessio Squassina
- Department of Biomedical Sciences, University of Cagliari
- Thomas Stamm
- Department of Psychiatry and Psychotherapy, Charité— Universitätsmedizin Berlin, Campus Charité Mitte
- Pavla Stopkova
- National Institute of Mental Health
- Sarah K. Tighe
- Department of Psychiatry, University of Iowa
- Alfonso Tortorella
- Department of Psychiatry, University of Naples SUN
- Gustavo Turecki
- Douglas Mental Health University Institute, McGill University
- Eduard Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII
- Julia Volkert
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt—Goethe University
- Stephanie Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Naomi R. Wray
- The University of Queensland, Queensland Brain Institute
- Adam Wright
- School of Psychiatry, University of New South Wales, and Black Dog Institute
- L. Trevor Young
- Department of Psychiatry, University of Toronto
- Peter P. Zandi
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health
- John R. Kelsoe
- Department of Psychiatry, University of California San Diego
- DOI
- https://doi.org/10.1038/s41398-024-02811-4
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 9
Abstract
Abstract Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
