International Journal of Bipolar Disorders (Jun 2024)
Exploring the genetics of lithium response in bipolar disorders
- Marisol Herrera-Rivero,
- Mazda Adli,
- Kazufumi Akiyama,
- Nirmala Akula,
- Azmeraw T. Amare,
- Raffaella Ardau,
- Bárbara Arias,
- Jean-Michel Aubry,
- Lena Backlund,
- Frank Bellivier,
- Antonio Benabarre,
- Susanne Bengesser,
- Abesh Kumar Bhattacharjee,
- Joanna M. Biernacka,
- Armin Birner,
- Micah Cearns,
- Pablo Cervantes,
- Hsi-Chung Chen,
- Caterina Chillotti,
- Sven Cichon,
- Scott R. Clark,
- Francesc Colom,
- Cristiana Cruceanu,
- Piotr M. Czerski,
- Nina Dalkner,
- Franziska Degenhardt,
- Maria Del Zompo,
- J. Raymond DePaulo,
- Bruno Etain,
- Peter Falkai,
- Ewa Ferensztajn-Rochowiak,
- Andreas J. Forstner,
- Josef Frank,
- Louise Frisén,
- Mark A. Frye,
- Janice M. Fullerton,
- Carla Gallo,
- Sébastien Gard,
- Julie S. Garnham,
- Fernando S. Goes,
- Maria Grigoroiu-Serbanescu,
- Paul Grof,
- Ryota Hashimoto,
- Roland Hasler,
- Joanna Hauser,
- Urs Heilbronner,
- Stefan Herms,
- Per Hoffmann,
- Liping Hou,
- Yi-Hsiang Hsu,
- Stephane Jamain,
- Esther Jiménez,
- Jean-Pierre Kahn,
- Layla Kassem,
- Tadafumi Kato,
- John Kelsoe,
- Sarah Kittel-Schneider,
- Po-Hsiu Kuo,
- Ichiro Kusumi,
- Barbara König,
- Gonzalo Laje,
- Mikael Landén,
- Catharina Lavebratt,
- Marion Leboyer,
- Susan G. Leckband,
- Mario Maj,
- Mirko Manchia,
- Cynthia Marie-Claire,
- Lina Martinsson,
- Michael J. McCarthy,
- Susan L. McElroy,
- Vincent Millischer,
- Marina Mitjans,
- Francis M. Mondimore,
- Palmiero Monteleone,
- Caroline M. Nievergelt,
- Tomas Novák,
- Markus M. Nöthen,
- Claire O’Donovan,
- Norio Ozaki,
- Sergi Papiol,
- Andrea Pfennig,
- Claudia Pisanu,
- James B. Potash,
- Andreas Reif,
- Eva Reininghaus,
- Hélène Richard-Lepouriel,
- Gloria Roberts,
- Guy A. Rouleau,
- Janusz K. Rybakowski,
- Martin Schalling,
- Peter R. Schofield,
- Klaus Oliver Schubert,
- Eva C. Schulte,
- Barbara W. Schweizer,
- Giovanni Severino,
- Tatyana Shekhtman,
- Paul D. Shilling,
- Katzutaka Shimoda,
- Christian Simhandl,
- Claire M. Slaney,
- Alessio Squassina,
- Thomas Stamm,
- Pavla Stopkova,
- Fabian Streit,
- Fasil Tekola-Ayele,
- Anbupalam Thalamuthu,
- Alfonso Tortorella,
- Gustavo Turecki,
- Julia Veeh,
- Eduard Vieta,
- Biju Viswanath,
- Stephanie H. Witt,
- Peter P. Zandi,
- Martin Alda,
- Michael Bauer,
- Francis J. McMahon,
- Philip B. Mitchell,
- Marcella Rietschel,
- Thomas G. Schulze,
- Bernhard T. Baune
Affiliations
- Marisol Herrera-Rivero
- Department of Psychiatry, University of Münster and Joint Institute for Individualisation in a Changing Environment (JICE), University of Münster and Bielefeld University
- Mazda Adli
- Department of Psychiatry and Psychotherapy, Charité, Universitätsmedizin Berlin
- 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
- Azmeraw T. Amare
- Discipline of Psychiatry, School of Medicine, University of Adelaide
- Raffaella Ardau
- Unit of Clinical Pharmacology, Hospital University Agency of Cagliari
- Bárbara Arias
- Unitat de Zoologia i Antropologia Biològica (Dpt. Biologia Evolutiva, Ecologia i Ciències Ambientals), Facultat de Biologia and Institut de Biomedicina (IBUB), University of Barcelona, CIBERSAM
- Jean-Michel Aubry
- Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals
- Lena Backlund
- Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute
- Frank Bellivier
- Département de Psychiatrie et de Médecine Addictologique, INSERM UMR-S 1144, Université Paris Cité, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière, F. Widal
- Antonio Benabarre
- Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM
- Susanne Bengesser
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, 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
- Armin Birner
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz
- Micah Cearns
- Discipline of Psychiatry, School of Medicine, University of Adelaide
- Pablo Cervantes
- 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
- Human Genomics Research Group, Department of Biomedicine, University Hospital Basel
- Scott R. Clark
- Discipline of Psychiatry, School of Medicine, University of Adelaide
- Francesc Colom
- Mental Health Research Group, IMIM-Hospital del Mar
- Cristiana Cruceanu
- Douglas Mental Health University Institute, McGill University
- Piotr M. Czerski
- Psychiatric Genetic Unit, Poznan University of Medical Sciences
- Nina Dalkner
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz
- Franziska Degenhardt
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Maria Del Zompo
- Department of Biomedical Sciences, University of Cagliari
- J. Raymond DePaulo
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Bruno Etain
- Département de Psychiatrie et de Médecine Addictologique, INSERM UMR-S 1144, Université Paris Cité, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière, F. Widal
- Peter Falkai
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich
- Ewa Ferensztajn-Rochowiak
- Department of Adult Psychiatry, Poznan University of Medical Sciences
- Andreas J. Forstner
- Institute of Neuroscience and Medicine (INM-1), Research Center Jülich
- Josef Frank
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Louise Frisén
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet
- Mark A. Frye
- Department of Psychiatry and Psychology, Mayo Clinic
- Janice M. Fullerton
- Neuroscience Research, Australia and School of Biomedical Sciences, University of New South Wales
- Carla Gallo
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Sébastien Gard
- Service de Psychiatrie, Hôpital 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 Clinical Psychiatric Hospital
- Paul Grof
- Mood Disorders Center of Ottawa
- Ryota Hashimoto
- Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry
- Roland Hasler
- Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals
- Joanna Hauser
- Psychiatric Genetic Unit, Poznan University of Medical Sciences
- Urs Heilbronner
- Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich
- Stefan Herms
- Human Genomics Research Group, Department of Biomedicine, University Hospital Basel
- Per Hoffmann
- Human Genomics Research Group, Department of Biomedicine, University Hospital Basel
- Liping Hou
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Yi-Hsiang Hsu
- Program for Quantitative Genomics, Harvard School of Public Health and HSL Institute for Aging Research, Harvard Medical School
- Stephane Jamain
- Univ. Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental
- 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 - Université
- Layla Kassem
- Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services
- Tadafumi Kato
- Department of Psychiatry & Behavioral Science, Graduate School of Medicine, Juntendo University
- John Kelsoe
- Department of Psychiatry, University of California San Diego
- Sarah Kittel-Schneider
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Würzburg
- Po-Hsiu Kuo
- Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University
- Ichiro Kusumi
- Department of Psychiatry, Hokkaido University Graduate School of Medicine
- Barbara König
- Department of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen
- 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 and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute
- Marion Leboyer
- Univ. Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, AP-HP, Mondor University Hospital, DMU Impact, Fondation FondaMental
- Susan G. Leckband
- Office of Mental Health, VA San Diego Healthcare System
- Mario Maj
- Department of Psychiatry, University of Campania ‘Luigi Vanvitelli’
- Mirko Manchia
- Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari
- Cynthia Marie-Claire
- Université Paris Cité, Inserm UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie
- Lina Martinsson
- Department of Clinical Neurosciences, Karolinska Institutet
- Michael J. McCarthy
- Department of Psychiatry, University of California San Diego
- Susan L. McElroy
- Department of Psychiatry, Lindner Center of Hope/University of Cincinnati
- Vincent Millischer
- Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute
- Marina Mitjans
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III
- Francis M. Mondimore
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Palmiero Monteleone
- Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno
- Caroline M. Nievergelt
- Department of Psychiatry, University of California San Diego
- Tomas Novák
- National Institute of Mental Health
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- Claire O’Donovan
- Department of Psychiatry, Dalhousie University
- Norio Ozaki
- Department of Psychiatry & Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine
- Sergi Papiol
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich
- Andrea Pfennig
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden
- Claudia Pisanu
- Department of Biomedical Sciences, University of Cagliari
- James B. Potash
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt
- Eva Reininghaus
- Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz
- Hélène Richard-Lepouriel
- Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals
- Gloria Roberts
- School of Psychiatry, University of New South Wales
- 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 and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute
- Peter R. Schofield
- Neuroscience Research, Australia and School of Biomedical Sciences, University of New South Wales
- Klaus Oliver Schubert
- Discipline of Psychiatry, School of Medicine, University of Adelaide
- Eva C. Schulte
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich
- Barbara W. Schweizer
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- 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
- Katzutaka Shimoda
- Department of Psychiatry, Dokkyo Medical University School of Medicine
- Christian Simhandl
- Medical Faculty, Bipolar Center Wiener Neustadt, Sigmund Freud University
- 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
- Pavla Stopkova
- National Institute of Mental Health
- Fabian Streit
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Fasil Tekola-Ayele
- Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
- Anbupalam Thalamuthu
- Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales
- Alfonso Tortorella
- Department of Psychiatry, University of Perugia
- Gustavo Turecki
- Douglas Mental Health University Institute, McGill University
- Julia Veeh
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt
- Eduard Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII
- Biju Viswanath
- Department of Psychiatry, National Institute of Mental Health and Neurosciences
- Stephanie H. Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Peter P. Zandi
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health
- Martin Alda
- Department of Psychiatry, Dalhousie University
- Michael Bauer
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden
- 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
- Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg
- Thomas G. Schulze
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University
- Bernhard T. Baune
- Department of Psychiatry, University of Münster and Joint Institute for Individualisation in a Changing Environment (JICE), University of Münster and Bielefeld University
- DOI
- https://doi.org/10.1186/s40345-024-00341-y
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 11
Abstract
Abstract Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
Keywords
