Biological Psychiatry Global Open Science (Sep 2025)
Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder
- Nigussie T. Sharew,
- Scott R. Clark,
- Sergi Papiol,
- Urs Heilbronner,
- Franziska Degenhardt,
- Janice M. Fullerton,
- Liping Hou,
- Tatyana Shekhtman,
- Mazda Adli,
- Nirmala Akula,
- Kazufumi Akiyama,
- Raffaella Ardau,
- Bárbara Arias,
- Roland Hasler,
- Hélène Richard-Lepouriel,
- Nader Perroud,
- Lena Backlund,
- Abesh Kumar Bhattacharjee,
- Frank Bellivier,
- Antonio Benabarre,
- Susanne Bengesser,
- Joanna M. Biernacka,
- Armin Birner,
- Cynthia Marie-Claire,
- Pablo Cervantes,
- Hsi-Chung Chen,
- Caterina Chillotti,
- Sven Cichon,
- Cristiana Cruceanu,
- Piotr M. Czerski,
- Nina Dalkner,
- Maria Del Zompo,
- J. Raymond DePaulo,
- Bruno Étain,
- Stephane Jamain,
- Peter Falkai,
- Andreas J. Forstner,
- Louise Frisen,
- Mark A. Frye,
- Sébastien Gard,
- Julie S. Garnham,
- Fernando S. Goes,
- Maria Grigoroiu-Serbanescu,
- Andreas J. Fallgatter,
- Sophia Stegmaier,
- Thomas Ethofer,
- Silvia Biere,
- Kristiyana Petrova,
- Ceylan Schuster,
- Kristina Adorjan,
- Monika Budde,
- Maria Heilbronner,
- Janos L. Kalman,
- Mojtaba Oraki Kohshour,
- Daniela Reich-Erkelenz,
- Sabrina K. Schaupp,
- Eva C. Schulte,
- Fanny Senner,
- Thomas Vogl,
- Ion-George Anghelescu,
- Volker Arolt,
- Udo Dannlowski,
- Detlef E. Dietrich,
- Christian Figge,
- Markus Jäger,
- Fabian U. Lang,
- Georg Juckel,
- Carsten Konrad,
- Jens Reimer,
- Max Schmauß,
- Andrea Schmitt,
- Carsten Spitzer,
- Martin von Hagen,
- Jens Wiltfang,
- Jörg Zimmermann,
- Till F.M. Andlauer,
- Andre Fischer,
- Felix Bermpohl,
- Philipp Ritter,
- Silke Matura,
- Anna Gryaznova,
- Irina Falkenberg,
- Cüneyt Yildiz,
- Tilo Kircher,
- Julia Schmidt,
- Marius Koch,
- Kathrin Gade,
- Sarah Trost,
- Ida S. Haussleiter,
- Martin Lambert,
- Anja C. Rohenkohl,
- Vivien Kraft,
- Paul Grof,
- Ryota Hashimoto,
- Joanna Hauser,
- Stefan Herms,
- Per Hoffmann,
- Esther Jiménez,
- Jean-Pierre Kahn,
- Layla Kassem,
- Po-Hsiu Kuo,
- Tadafumi Kato,
- John Kelsoe,
- Sarah Kittel-Schneider,
- Ewa Ferensztajn-Rochowiak,
- Barbara König,
- Ichiro Kusumi,
- Gonzalo Laje,
- Mikael Landén,
- Catharina Lavebratt,
- Marion Leboyer,
- Susan G. Leckband,
- Alfonso Tortorella,
- Mirko Manchia,
- Lina Martinsson,
- Michael J. McCarthy,
- Susan McElroy,
- Francesc Colom,
- Vincent Millischer,
- Marina Mitjans,
- Francis M. Mondimore,
- Palmiero Monteleone,
- Caroline M. Nievergelt,
- Markus M. Nöthen,
- Tomas Novák,
- Claire O’Donovan,
- Norio Ozaki,
- Andrea Pfennig,
- Claudia Pisanu,
- James B. Potash,
- Andreas Reif,
- Eva Reininghaus,
- Guy A. Rouleau,
- Janusz K. Rybakowski,
- Martin Schalling,
- Peter R. Schofield,
- Barbara W. Schweizer,
- Giovanni Severino,
- Paul D. Shilling,
- Katzutaka Shimoda,
- Christian Simhandl,
- Claire M. Slaney,
- Alessio Squassina,
- Thomas Stamm,
- Pavla Stopkova,
- Mario Maj,
- Gustavo Turecki,
- Eduard Vieta,
- Julia Veeh,
- Biju Viswanath,
- Stephanie H. Witt,
- Adam Wright,
- Peter P. Zandi,
- Philip B. Mitchell,
- Michael Bauer,
- Martin Alda,
- Marcella Rietschel,
- Francis J. McMahon,
- Thomas G. Schulze,
- Bernhard T. Baune,
- Klaus Oliver Schubert,
- Azmeraw T. Amare
Affiliations
- Nigussie T. Sharew
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Asrat Woldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
- Scott R. Clark
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
- Sergi Papiol
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany
- Urs Heilbronner
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Franziska Degenhardt
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, Rheinische Kliniken, Essen, Germany
- Janice M. Fullerton
- Neuroscience Research Australia, Sydney, New South Wales, Australia; School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, Australia
- Liping Hou
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland
- Tatyana Shekhtman
- Department of Psychiatry, University of California San Diego, San Diego, California
- Mazda Adli
- Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Nirmala Akula
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland
- Kazufumi Akiyama
- Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Tochigi, Japan
- Raffaella Ardau
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy
- Bárbara Arias
- Unitat de Zoologia i Antropologia Biològica (Dpt. Biologia Evolutiva, Ecologia i Ciències Ambientals), Facultat de Biologia and Institut de Biomedicina, University of Barcelona, CIBERSAM, Barcelona, Spain
- Roland Hasler
- Department of Psychiatry, Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland
- Hélène Richard-Lepouriel
- Department of Psychiatry, Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland
- Nader Perroud
- Department of Psychiatry, Mood Disorders Unit, HUG - Geneva University Hospitals, Geneva, Switzerland
- Lena Backlund
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
- Abesh Kumar Bhattacharjee
- Department of Psychiatry, University of California San Diego, San Diego, California
- Frank Bellivier
- Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 1144, Université Paris Cité, Département de Psychiatrie et de Médecine Addictologique, L'Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France
- Antonio Benabarre
- Bipolar and Depressive Disorders Program, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
- Susanne Bengesser
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria
- Joanna M. Biernacka
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
- Armin Birner
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria
- Cynthia Marie-Claire
- Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 1144, Université Paris Cité, Département de Psychiatrie et de Médecine Addictologique, L'Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France; Université Paris Cité, Inserm, Optimisation Thérapeutique en Neuropsychopharmacologie, Paris, France
- Pablo Cervantes
- Neuromodulation Unit, McGill University Health Centre, Montreal, Quebec, Canada
- Hsi-Chung Chen
- Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan
- Caterina Chillotti
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy
- Sven Cichon
- Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
- Cristiana Cruceanu
- Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
- Piotr M. Czerski
- Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznań, Poland
- Nina Dalkner
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria
- Maria Del Zompo
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- J. Raymond DePaulo
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
- Bruno Étain
- Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 1144, Université Paris Cité, Département de Psychiatrie et de Médecine Addictologique, L'Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France
- Stephane Jamain
- Inserm U955, Fondation FondaMental, Translational Psychiatry Laboratory, Créteil, France
- Peter Falkai
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany
- Andreas J. Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Institute of Neuroscience and Medicine, Research Center Jülich, Jülich, Germany
- Louise Frisen
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
- Mark A. Frye
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
- Sébastien Gard
- Pôle de Psychiatrie Générale Universitaire, Hôpital Charles Perrens, Bordeaux, France
- Julie S. Garnham
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
- Fernando S. Goes
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
- Maria Grigoroiu-Serbanescu
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
- Andreas J. Fallgatter
- Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania
- Sophia Stegmaier
- University Department of Psychiatry and Psychotherapy Tuebingen, University of Tübingen, Tübingen, Germany
- Thomas Ethofer
- Department of General Psychiatry, University of Tübingen, Tübingen, Germany; Department of Biomedical Resonance, University of Tübingen, Tübingen, Germany
- Silvia Biere
- Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Frankfurt, Goethe University, Frankfurt, Germany
- Kristiyana Petrova
- Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Frankfurt, Goethe University, Frankfurt, Germany
- Ceylan Schuster
- Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Frankfurt, Goethe University, Frankfurt, Germany
- Kristina Adorjan
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapie, University of Bern, Bern, Switzerland
- Monika Budde
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Maria Heilbronner
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Janos L. Kalman
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany
- Mojtaba Oraki Kohshour
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Daniela Reich-Erkelenz
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Sabrina K. Schaupp
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Eva C. Schulte
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany
- Fanny Senner
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany
- Thomas Vogl
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Ion-George Anghelescu
- Department of Psychiatry and Psychotherapy, Mental Health Institute Berlin, Berlin, Germany
- Volker Arolt
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- Udo Dannlowski
- Institute for Translational Psychiatry, University of Münster, Münster, Germany
- Detlef E. Dietrich
- AMEOS Clinical Center Hildesheim, Hildesheim, Germany; Center for Systems Neuroscience, Hannover, Germany
- Christian Figge
- Karl-Jaspers Clinic, European Medical School Oldenburg-Groningen, Oldenburg, Germany
- Markus Jäger
- Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany
- Fabian U. Lang
- Department of Psychiatry II, Ulm University, Bezirkskrankenhaus Günzburg, Günzburg, Germany
- Georg Juckel
- Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
- Carsten Konrad
- Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum, Rotenburg, Germany
- Jens Reimer
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Psychiatry, Health North Hospital Group, Bremen, Germany
- Max Schmauß
- Department of Psychiatry and Psychotherapy, Bezirkskrankenhaus Augsburg, Augsburg, Germany
- Andrea Schmitt
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University Munich, Munich, Germany; Laboratory of Neuroscience, Institute of Psychiatry, University of Sao Paulo, São Paulo, Brazil
- Carsten Spitzer
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Rostock, Rostock, Germany
- Martin von Hagen
- Clinic for Psychiatry and Psychotherapy, Clinical Center Werra-Meißner, Eschwege, Germany
- Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases, University of Göttingen, Göttingen, Germany
- Jörg Zimmermann
- Psychiatrieverbund Oldenburger Land GmbH, Karl-Jaspers-Klinik, Bad Zwischenahn, Germany
- Till F.M. Andlauer
- Department of Neurology, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
- Andre Fischer
- German Center for Neurodegenerative Diseases, University of Göttingen, Göttingen, Germany
- Felix Bermpohl
- Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Philipp Ritter
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
- Silke Matura
- Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Frankfurt, Goethe University, Frankfurt, Germany
- Anna Gryaznova
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
- Irina Falkenberg
- Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany
- Cüneyt Yildiz
- Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany
- Tilo Kircher
- Department of Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany
- Julia Schmidt
- Institute for Medical Informatics, University Medical Center Göttingen, Göttingen, Germany
- Marius Koch
- Institute for Medical Informatics, University Medical Center Göttingen, Göttingen, Germany
- Kathrin Gade
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
- Sarah Trost
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
- Ida S. Haussleiter
- Department of Psychiatry, Ruhr University Bochum, LWL University Hospital, Bochum, Germany
- Martin Lambert
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Anja C. Rohenkohl
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Vivien Kraft
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Paul Grof
- Mood Disorders Center of Ottawa, Ottawa, Ontario, Canada
- Ryota Hashimoto
- Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
- Joanna Hauser
- Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznań, Poland
- Stefan Herms
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
- Per Hoffmann
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
- Esther Jiménez
- Bipolar and Depressive Disorders Program, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
- Jean-Pierre Kahn
- Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy, Université de Lorraine, Nancy, France
- Layla Kassem
- Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Po-Hsiu Kuo
- Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Tadafumi Kato
- Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Saitama, Japan
- John Kelsoe
- Department of Psychiatry, University of California San Diego, San Diego, California
- Sarah Kittel-Schneider
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany; Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital of Würzburg, Würzburg, Germany
- Ewa Ferensztajn-Rochowiak
- Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland
- Barbara König
- Department of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen, Neunkirchen, Austria
- Ichiro Kusumi
- Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
- Gonzalo Laje
- Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
- Mikael Landén
- Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Catharina Lavebratt
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
- Marion Leboyer
- Inserm U955, Translational Psychiatry Laboratory, Université Paris-Est-Créteil, Department of Psychiatry and Addictology of Mondor University Hospital, AP-HP, Fondation FondaMental, Créteil, France
- Susan G. Leckband
- Office of Mental Health, VA San Diego Healthcare System, San Diego, California
- Alfonso Tortorella
- Department of Psychiatry, University of Perugia, Perugia, Italy
- Mirko Manchia
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
- Lina Martinsson
- Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden
- Michael J. McCarthy
- Department of Psychiatry, University of California San Diego, San Diego, California; Department of Psychiatry, VA San Diego Healthcare System, San Diego, California
- Susan McElroy
- Department of Psychiatry, Lindner Center of Hope, University of Cincinnati, Mason, Ohio
- Francesc Colom
- Mental Health Research Group, Hospital del Mar Medical Research Institute, Barcelona, Catalonia, Spain; Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Vincent Millischer
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Marina Mitjans
- Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain; CIBERSAM, Instituto de Salud Carlos III, Madrid, Spain; Institut de Biomedicina de la Universität de Barcelona, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
- Francis M. Mondimore
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
- Palmiero Monteleone
- Neurosciences Section, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, Salerno, Italy; Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Caroline M. Nievergelt
- Department of Psychiatry, University of California San Diego, San Diego, California
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany
- Tomas Novák
- National Institute of Mental Health, Klecany, Czechia
- Claire O’Donovan
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
- Norio Ozaki
- Department of Psychiatry & Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Andrea Pfennig
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
- Claudia Pisanu
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- James B. Potash
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
- Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany
- Eva Reininghaus
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria
- Guy A. Rouleau
- Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
- Janusz K. Rybakowski
- Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland
- Martin Schalling
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
- Peter R. Schofield
- Neuroscience Research Australia, Sydney, New South Wales, Australia; School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, Australia
- Barbara W. Schweizer
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland
- Giovanni Severino
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Paul D. Shilling
- Department of Psychiatry, University of California San Diego, San Diego, California
- Katzutaka Shimoda
- Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan
- Christian Simhandl
- Bipolar Center Wiener Neustadt, Sigmund Freud University, Medical Faculty, Vienna, Austria
- Claire M. Slaney
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
- Alessio Squassina
- Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
- Thomas Stamm
- Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany; Department of Clinical Psychiatry and Psychotherapy, Brandenburg Medical School, Brandenburg, Germany
- Pavla Stopkova
- National Institute of Mental Health, Klecany, Czechia
- Mario Maj
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Gustavo Turecki
- Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada
- Eduard Vieta
- Bipolar and Depressive Disorders Program, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
- Julia Veeh
- Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden
- Biju Viswanath
- Department of Psychiatry, National Institute of Mental Health and Neuroscience, Bangalore, India
- Stephanie H. Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Adam Wright
- School of Psychiatry, University of New South Wales and Black Dog Institute, Sydney, New South Wales, Australia
- Peter P. Zandi
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Philip B. Mitchell
- School of Psychiatry, University of New South Wales and Black Dog Institute, Sydney, New South Wales, Australia
- Michael Bauer
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany
- Martin Alda
- Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; National Institute of Mental Health, Klecany, Czechia
- Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- Francis J. McMahon
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland
- Thomas G. Schulze
- Institute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany; Intramural Research Program, National Institute of Mental Health, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Department of Psychiatry and Behavioral Sciences, Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York; Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University Göttingen, Göttingen, Germany
- Bernhard T. Baune
- Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany; Department of Psychiatry, Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
- Klaus Oliver Schubert
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Northern Adelaide Local Health Network, Mental Health Services, Adelaide, South Australia, Australia
- Azmeraw T. Amare
- Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Address correspondence to Azmeraw T. Amare, Ph.D.
- DOI
- https://doi.org/10.1016/j.bpsgos.2025.100558
- Journal volume & issue
-
Vol. 5,
no. 5
p. 100558
Abstract
Background: Polygenic scores (PGSs) hold the potential to identify patients who respond favorably to specific psychiatric treatments. However, their biological interpretation remains unclear. In this study, we developed pathway-specific PGSs (PSPGSs) for lithium response and assessed their association with clinical lithium response in patients with bipolar disorder. Methods: Using sets of genes involved in pathways affected by lithium, we developed 9 PSPGSs and evaluated their associations with lithium response in the International Consortium on Lithium Genetics (ConLi+Gen) (N = 2367), with validation in combined PsyCourse (Pathomechanisms and Signatures in the Longitudinal Course of Psychosis) (N = 105) and BipoLife (N = 102) cohorts. The association between each PSPGS and lithium response—defined both as a continuous ALDA score and a categorical outcome (good vs. poor responses)—was evaluated using regression models, with adjustment for confounders. The cutoff for a significant association was p < .05 after multiple testing correction. Results: The PGSs for acetylcholine, GABA (gamma-aminobutyric acid), and mitochondria were associated with response to lithium in both categorical and continuous outcomes. However, the PGSs for calcium channel, circadian rhythm, and GSK (glycogen synthase kinase) were associated only with the continuous outcome. Each score explained 0.29% to 1.91% of the variance in the categorical and 0.30% to 1.54% of the variance in the continuous outcomes. A multivariate model combining PSPGSs that showed significant associations in the univariate analysis (combined PSPGS) increased the percentage of variance explained (R2) to 3.71% and 3.18% for the categorical and continuous outcomes, respectively. Associations for PGSs for GABA and circadian rhythm were replicated. Patients with the highest genetic loading (10th decile) for acetylcholine variants were 3.03 times more likely (95% CI, 1.95 to 4.69) to show a good lithium response (categorical outcome) than patients with the lowest genetic loading (1st decile). Conclusions: PSPGSs achieved predictive performance comparable to the conventional genome-wide PGSs, with the added advantage of biological interpretability using a smaller list of genetic variants.
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