Trial reportJAMA psychiatry2018
Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph
Trial report in JAMA psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 6 pooled it
13.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 6 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Genome-wide association analyses of borderline personality disorder identify 11 loci and highlight shared risk with mental and somatic disorders.Nature genetics · 2026Pooled it
- Pharmacogenomic scores in psychiatry: systematic review of current evidence.Translational psychiatry · 2024Pooled it
- Review and Consensus on Pharmacogenomic Testing in Psychiatry.Pharmacopsychiatry · 2021Pooled it
- A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.Nature communications · 2019Pooled it
- The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- Pooled it
- Association between Copy Number Variation and Response to Social Skills Training in Autism Spectrum Disorder.Scientific reports · 2019Trial
- Response to therapeutic sleep deprivation: a naturalistic study of clinical and genetic factors and post-treatment depressive symptom trajectory.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Trial
- Identification of comprehensive genetic factors, pathways, and shared genetic architecture of putamen volume in adolescent cohort.Translational psychiatry · 2026Article
- Polygenic risk scores in pharmacogenomics: methodological challenges, current applications, and perspectives for clinical implementation.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Lithium Therapeutic Functions: An Update on Pharmacokinetics, Pathophysiological Mechanisms of Action, Toxicity, and Side Effects.Molecular neurobiology · 2026Review
- Genetics to Improve Outcomes in Schizophrenia (GENios): A within-case molecular genetic study protocol.PloS one · 2026Article
- Toll-like receptor 3 (TLR 3) polymorphisms predisposition to schizophrenia and bipolar disorder.Molecular biology reports · 2025Article
- Polygenic Contributions to Lithium Augmentation Outcomes in Unipolar Depression.JAMA psychiatry · 2025Article
- A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Genetics of Response to ECT, TMS, Ketamine and Esketamine.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Review
- Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.Biological psychiatry global open science · 2025Article
- The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids.Cellular and molecular life sciences : CMLS · 2025Article
- Translating Molecular Psychiatry: From Biomarkers to Personalized Therapies-A Narrative Review.International journal of molecular sciences · 2025Review
- The Mechanisms of Lithium Action: The Old and New Findings.Pharmaceuticals (Basel, Switzerland) · 2025Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
113 authors at 20 institutions in 15 countries.
International Consortium on Lithium Genetics (ConLi+Gen)
Azmeraw T AmareDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Klaus Oliver SchubertDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Liping HouIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Scott R ClarkDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Sergi PapiolInstitute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig-Maximilian University of Munich, Munich, Germany.
Urs HeilbronnerInstitute of Psychiatric Phenomics and Genomics, University Hospital, Ludwig-Maximilian University of Munich, Munich, Germany.
Franziska DegenhardtInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Fasil Tekola-AyeleEpidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Yi-Hsiang HsuHebrew SeniorLife Institute for Aging Research, Harvard Medical School, Boston, Massachusetts.
Tatyana ShekhtmanDepartment of Psychiatry, University of California San Diego.
Mazda AdliDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Nirmala AkulaIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Kazufumi AkiyamaDepartment of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
Raffaella ArdauUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
Bárbara AriasUnitat de Zoologia i Antropologia Biològica (Dpt Biologia Evolutiva, Ecologia i Ciències Ambientals), Facultat de Biologia and Institut de Biomedicina, University of Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain.
Jean-Michel AubryDepartment of Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, Switzerland.
Lena BacklundDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Abesh Kumar BhattacharjeeDepartment of Psychiatry, University of California San Diego.
Frank BellivierInstitut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifique 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F. Widal, Paris, France.
Antonio BenabarreBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red Salud Mental, Barcelona, Catalonia, Spain.
Susanne BengesserDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.
Joanna M BiernackaDepartment of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Armin BirnerDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.
Clara Brichant-PetitjeanInstitut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifique 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F. Widal, Paris, France.
Pablo CervantesThe Neuromodulation Unit, McGill University Health Centre, Montreal, Canada.
Hsi-Chung ChenDepartment of Psychiatry and Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
Caterina ChillottiUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
Sven CichonInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Cristiana CruceanuDouglas Mental Health University Institute, McGill University, Montreal, Canada.
Piotr M CzerskiPsychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
Nina DalknerDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.
Alexandre DayerDepartment of Psychiatry, Mood Disorders Unit, Geneva University Hospitals, Geneva, Switzerland.
Maria Del ZompoDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
J Raymond DePauloDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.
Bruno ÉtainInstitut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifique 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Saint-Louis-Lariboisière-F. Widal, Paris, France.
Peter FalkaiDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilian University of Munich, Munich, Germany.
Andreas J ForstnerInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Louise FrisenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota.
Janice M FullertonNeuroscience Research Australia, Sydney, New South Wales, Australia.
Sébastien GardService de Psychiatrie, Hôpital Charles Perrens, Bordeaux, France.
Julie S GarnhamDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Fernando S GoesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.
Maria Grigoroiu-SerbanescuBiometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.
Paul GrofMood Disorders Center of Ottawa, Ontario, Canada.
Ryota HashimotoMolecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.
Joanna HauserPsychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.
Stefan HermsInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Per HoffmannInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Andrea HofmannInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Stephane JamainInstitut National de la Santé et de la Recherche Médicale Unité 955, Psychiatrie Translationnelle, Créteil, France.
Esther JiménezBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red Salud Mental, Barcelona, Catalonia, Spain.
Jean-Pierre KahnService de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy, Université de Lorraine, Nancy, France.
Layla KassemIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Po-Hsiu KuoDepartment of Public Health and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Tadafumi KatoLaboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
John KelsoeDepartment of Psychiatry, University of California San Diego.
Sarah Kittel-SchneiderDepartment of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Sebastian KliwickiDepartment of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Barbara KönigDepartment of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen, Neunkirchen, Austria.
Ichiro KusumiDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Gonzalo LajeIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Mikael LandénInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden.
Catharina LavebrattDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Marion LeboyerInserm U955, Translational Psychiatry Laboratory, Université Paris-Est-Créteil, Department of Psychiatry and Addictology of Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, Hôpital Albert Chenevier-Henri Mondor, Pôle de Psychiatrie, Créteil, France.
Susan G LeckbandDepartment of Pharmacy, Veterans Affairs San Diego Healthcare System, San Diego, California.
Alfonso TortorellaDepartment of Psychiatry, University of Perugia, Perugia, Italy.
Mirko ManchiaSection of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Lina MartinssonDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Michael J McCarthyDepartment of Psychiatry, University of California San Diego.
Susan McElroyDepartment of Psychiatry, Lindner Center of Hope and University of Cincinnati, Mason, Ohio.
Francesc ColomBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red Salud Mental, Barcelona, Catalonia, Spain.
Marina MitjansCentro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain.
Francis M MondimoreDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.
Palmiero MonteleoneNeurosciences Section, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego.
Markus M NöthenInstitute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
Tomas NovákNational Institute of Mental Health, Klecany, Czech Republic.
Claire O'DonovanDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Norio OzakiDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Urban ÖsbyDepartment of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Andrea PfennigDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Germany.
James B PotashDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.
Andreas ReifLaboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.
Eva ReininghausDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.
Guy A RouleauMontreal Neurological Institute and Hospital, McGill University, Montreal, Canada.
Janusz K RybakowskiDepartment of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Martin SchallingDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Peter R SchofieldNeuroscience Research Australia, Sydney, New South Wales, Australia.
Barbara W SchweizerDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland.
Giovanni SeverinoDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Paul D ShillingDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Katzutaka ShimodaDepartment of Psychiatry, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Christian SimhandlBipolar Center Wiener Neustadt, Sigmund Freud University, Medical Faculty, Vienna, Austria.
Claire M SlaneyDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Alessio SquassinaDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Thomas StammDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Pavla StopkovaNational Institute of Mental Health, Klecany, Czech Republic.
Mario MajDepartment of Psychiatry, Second University of Naples, Naples, Italy.
Gustavo TureckiDouglas Mental Health University Institute, McGill University, Montreal, Canada.
Eduard VietaBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red Salud Mental, Barcelona, Catalonia, Spain.
Julia VolkertDepartment of Psychiatry, Psychosomatic Medicine, and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Stephanie WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Adam WrightSchool of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, New South Wales, Australia.
Peter P ZandiDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Philip B MitchellSchool of Psychiatry, University of New South Wales, and Black Dog Institute, Sydney, New South Wales, Australia.
Michael BauerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Germany.
Martin AldaDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Francis J McMahonIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Thomas G SchulzeIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland.
Bernhard T BauneDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
Johns Hopkins University · USDalhousie University · CAUniversity of Cagliari · ITUniversity of California, San Diego · USKarolinska Institutet · SELife & Brain (Germany) · DEMedical University of Graz · ATUniversity of Adelaide · AUAssistance Publique – Hôpitaux de Paris · FRCentro de Investigación Biomédica en Red de Salud Mental · ESKarolinska University Hospital · SELudwig-Maximilians-Universität München · DEMcGill University · CAPoznan University of Medical Sciences · PLUniversity Hospital Frankfurt · DEBlack Dog Institute · AUCharité - Universitätsmedizin Berlin · DEMayo Clinic · USNational Institute of Mental Health · CZNational Institute of Mental Health · US
Funding
Human Genetics of Addiction: A Study of Common and Specific FactorsK02DA021237 · NIDA · WASHINGTON UNIVERSITY · PI BIERUT, LAURA J. · 2007 to 2011
$567kOsteocalcin and Metabolic Risk Factors. The Framingham StudyR21AR056405 · NIAMS · HEBREW REHABILITATION CENTER FOR AGED · PI HSU, YI-HSIANG · 2010 to 2011
$377kNIAMS NIH HHS R21 AR056405NIDA NIH HHS K02 DA021237
Abstract
Importance: Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). Objectives: To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. Design, Setting, and Participants: A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. Main Outcomes and Measures: Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. Results: Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 × 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. Conclusions and Relevance: This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
Indexed as
Genome-Wide Association StudyAdultBipolar DisorderFemaleGenetic LoadGenotypeHLA AntigensHumansInflammationLithium CarbonateMaleMiddle AgedMultifactorial InheritanceSchizophreniaSchizophrenic PsychologyTreatment OutcomeHLA AntigensLithium Carbonate
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