Evidence map›Paper›PMID 34845190›Full record

SynthesisTranslational psychiatry2021

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients.

Klaus Oliver Schubert, Anbupalam Thalamuthu, Azmeraw T Amare, Joseph Frank, Fabian Streit, Mazda Adl, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias and 107 more

Erratum issuedOpen access · goldAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The impact of collider bias on genetic prediction in psychotic disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Moving toward precision and personalized treatment strategies in psychiatry.The international journal of neuropsychopharmacology · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Exploring the genetics of lithium response in bipolar disorders.International journal of bipolar disorders · 2024
    Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

117 authors at 20 institutions in 15 countries.

Klaus Oliver Schubert *Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0003-1690-0209
Anbupalam Thalamuthu *Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Azmeraw T Amare *Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-7940-0335
Joseph FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0003-4867-9465
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0003-1080-4339
Mazda AdlDepartment 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 & Human Services, Bethesda, MD, USA.
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 (IBUB), University of Barcelona, CIBERSAM, Barcelona, Spain.
Jean-Michel AubryDepartment of Psychiatry, Mood Disorders Unit, HUG-Geneva University Hospitals, Geneva, Switzerland.
Lena BacklundDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Abesh Kumar BhattacharjeeDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Frank BellivierINSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
Antonio BenabarreBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 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 Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-9350-4440
Armin BirnerDepartment of Psychiatry and Psychotherapeutic Medicine, Research Unit for bipolar affective disorder, Medical University of Graz, Graz, Austria.
Cynthia Marie-ClaireINSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
Micah CearnsDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Pablo CervantesThe Neuromodulation Unit, McGill University Health Centre, Montreal, QC, Canada.
Hsi-Chung ChenDepartment of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.
Caterina ChillottiUnit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.
Sven CichonHuman Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Scott R ClarkDiscipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0003-1640-5611
Cristiana CruceanuDouglas Mental Health University Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-7799-5531
Piotr M CzerskiPsychiatric Genetic Unit, Poznan University of Medical Sciences, Poznan, Poland.ORCID http://orcid.org/0000-0003-0745-5916
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, HUG-Geneva University Hospitals, Geneva, Switzerland.
Franziska DegenhardtInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.
Maria Del ZompoDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.ORCID http://orcid.org/0000-0001-9491-5938
J Raymond DePauloDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Bruno ÉtainINSERM UMR-S 1144, Université Paris Diderot, Département de Psychiatrie et de Médecine Addictologique, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-F.Widal, Paris, France.
Peter FalkaiDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
Andreas J ForstnerHuman Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1876-6368
Louise FrisenDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Mark A FryeDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-6997-4215
Janice M FullertonNeuroscience Research Australia, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-4014-4490
Sébastien GardService de psychiatrie, Hôpital Charles Perrens, Bordeaux, France.
Julie S GarnhamDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.ORCID http://orcid.org/0000-0002-7987-4995
Fernando S GoesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Maria Grigoroiu-SerbanescuBiometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.ORCID http://orcid.org/0000-0002-1304-6687
Paul GrofMood Disorders Center of Ottawa, Ottawa, ON, 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.ORCID http://orcid.org/0000-0002-6621-3493
Urs HeilbronnerInstitute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-7135-762X
Stefan HermsHuman Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2786-8200
Per HoffmannHuman Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Liping HouIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3972-245X
Yi-Hsiang HsuHSL Institute for Aging Research, Harvard Medical School, Boston, MA, USA.
Stephane JamainUniv Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, Créteil, France.ORCID http://orcid.org/0000-0002-4321-4100
Esther JiménezBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 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 & Human Services, Bethesda, MD, USA.
Po-Hsiu KuoDepartment of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Tadafumi KatoDepartment of Psychiatry & Behavioral Science, Juntendo University, Graduate School of Medicine, Tokyo, Japan.
John KelsoeDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-3013-2333
Sarah Kittel-SchneiderDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Ewa Ferensztajn-RochowiakDepartment 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.ORCID http://orcid.org/0000-0002-8747-5070
Gonzalo LajeIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Mikael LandénInstitute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-4496-6451
Catharina LavebrattDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-4987-2718
Marion LeboyerInserm U955, Translational Neuro-Psychiatry laboratory, Université Paris Est Créteil (UPEC), AP-HP, Department of Psychiatry and Addictology of Mondor University Hospital, AP-HP, Fondation FondaMental, Créteil, France.ORCID http://orcid.org/0000-0001-5473-3697
Susan G LeckbandOffice of Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
Mario MajDepartment of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
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, San Diego, CA, USA.
Susan McElroyDepartment of Psychiatry, Lindner Center of Hope / University of Cincinnati, Mason, OH, USA.
Francesc ColomMental Health Research Group, IMIM-Hospital del Mar, Barcelona, Catalonia, Spain.
Marina MitjansDepartament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Francis M MondimoreDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Palmiero MonteleoneDepartment of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0001-5766-8923
Markus M NöthenInstitute of Human Genetics, University of Bonn and Department of Genomics, Life & Brain Center, Bonn, Germany.ORCID http://orcid.org/0000-0002-8770-2464
Tomas NovákNational Institute of Mental Health, Klecany, Czech Republic.ORCID http://orcid.org/0000-0001-9156-9654
Claire O'DonovanDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Norio OzakiDepartment of Psychiatry & Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID http://orcid.org/0000-0002-7360-4898
Urban ÖsbyDepartment of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Sergi PapiolDepartment of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-9366-8728
Andrea PfennigDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Claudia PisanuDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.ORCID http://orcid.org/0000-0002-9151-4319
James B PotashDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Andreas ReifDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.ORCID http://orcid.org/0000-0002-0992-634X
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, QC, Canada.ORCID http://orcid.org/0000-0001-8403-1418
Janusz K RybakowskiDepartment of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Martin SchallingDepartment of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Peter R SchofieldNeuroscience Research Australia, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0003-2967-9662
Barbara W SchweizerDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
Giovanni SeverinoDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.ORCID http://orcid.org/0000-0002-6354-2662
Tatyana ShekhtmanDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.
Paul D ShillingDepartment of Psychiatry, University of California San Diego, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-0129-5504
Katzutaka ShimodaDepartment of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.ORCID http://orcid.org/0000-0002-9663-6243
Christian SimhandlBipolar Center Wiener Neustadt, Sigmund Freud University, Medical Faculty, Vienna, Austria.
Claire M SlaneyDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.
Alessio SquassinaDepartment of Biomedical Sciences, University of Cagliari, Cagliari, Italy.ORCID http://orcid.org/0000-0001-7415-7607
Thomas StammDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Pavla StopkovaNational Institute of Mental Health, Klecany, Czech Republic.
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, MD, USA.
Alfonso TortorellaDepartment of Psychiatry, University of Perugia, Perugia, Italy.
Gustavo TureckiDouglas Mental Health University Institute, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0003-4075-2736
Julia VeehDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.
Eduard VietaBipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0002-1571-1468
Gloria RobertsSchool of Psychiatry, University of New South Wales, Sydney, Australia.
Peter P ZandiDepartment of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Martin AldaDepartment of Psychiatry, Dalhousie University, Halifax, NS, Canada.ORCID http://orcid.org/0000-0001-9544-3944
Michael BauerDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.ORCID http://orcid.org/0000-0002-2666-859X
Francis J McMahonIntramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9469-305X
Philip B MitchellSchool of Psychiatry, University of New South Wales, Sydney, Australia.ORCID http://orcid.org/0000-0002-7954-5235
Thomas G SchulzeDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0001-6624-2975
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0002-5236-6149
Bernhard T BauneDepartment of Psychiatry and Psychotherapy, University of Münster, Münster, Germany. Bernhard.Baune@ukmuenster.de.ORCID http://orcid.org/0000-0001-6548-426X
Johns Hopkins University · USUnited States Department of Health and Human Services · USUniversity of Bonn · DEUniversity of Cagliari · ITUniversity of California San Diego · USCentro de Investigación Biomédica en Red de Salud Mental · ESDalhousie University · CAInserm · FRKarolinska University Hospital · SEUNSW Sydney · AUHeidelberg University · DEMedical University of Graz · ATPoznan University of Medical Sciences · PLThe University of Adelaide · AUGoethe University Frankfurt · DELudwig-Maximilians-Universität München · DECharité - Universitätsmedizin Berlin · DEDokkyo Medical University · JPDouglas Mental Health University Institute · CAKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi

Indexed as

Bipolar DisorderMajor Depressive DisorderSchizophreniaDepressionGenetic Predisposition to DiseaseHumansLithiumMultifactorial InheritanceRisk FactorsLithium

Identifiers

PMID34845190
PMCPMC8630000
OpenAlexW3215104146

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.