Exploring the genetics of lithium response in bipolar disorders.

Bipolar disorder Comorbidity Genetics Lithium treatment Psychiatric symptoms

Journal

International journal of bipolar disorders
ISSN: 2194-7511
Titre abrégé: Int J Bipolar Disord
Pays: Germany
ID NLM: 101622983

Informations de publication

Date de publication:
12 Jun 2024
Historique:
received: 28 11 2023
accepted: 02 05 2024
medline: 12 6 2024
pubmed: 12 6 2024
entrez: 12 6 2024
Statut: epublish

Résumé

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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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.

Identifiants

DOI: 10.1186/s40345-024-00341-y PMID: 38865039
pubmed: 38865039
doi: 10.1186/s40345-024-00341-y
pii: 10.1186/s40345-024-00341-y
doi:

Types de publication

Journal Article

Langues

eng

Pagination

20

Informations de copyright

© 2024. The Author(s).

Références

Amare AT, Schubert KO, International Consortium on Lithium Genetics (ConLi+Gen), et al. 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. JAMA Psychiatry. 2018;75(1):65–74. https://doi.org/10.1001/jamapsychiatry.2017.3433
Amare AT, Thalamuthu A, Schubert KO, et al. Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder. Mol Psychiatry. 2023. https://doi.org/10.1038/s41380-023-02149-1.10.1038/s41380-023-02149-1 .
doi: 10.1038/s41380-023-02149-1.10.1038/s41380-023-02149-1 pubmed: 37433967 pmcid: 11041653
Catak Z, Kocdemir E, Ugur K, et al. A novel biomarker renalase and its relationship with its substrates in schizophrenia. J Med Biochem. 2019;38(3):299–305. https://doi.org/10.2478/jomb-2018-0031 .
doi: 10.2478/jomb-2018-0031 pubmed: 31156340 pmcid: 6534954
Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7. https://doi.org/10.1186/s13742-015-0047-8 .
doi: 10.1186/s13742-015-0047-8 pubmed: 25722852 pmcid: 4342193
Chen PH, Hsiao CY, Chiang SJ, et al. Cardioprotective potential of lithium and role of fractalkine in euthymic patients with bipolar disorder. Aust N Z J Psychiatry. 2023;57(1):104–14. https://doi.org/10.1177/00048674211062532 .
doi: 10.1177/00048674211062532 pubmed: 34875897
Coombes BJ, Millischer V, Batzler A, et al. Association of attention-deficit/hyperactivity disorder and depression polygenic scores with lithium response: a consortium for lithium genetics study. Complex Psychiatry. 2021;7(3–4):80–9. https://doi.org/10.1159/000519707 .
doi: 10.1159/000519707 pubmed: 36408127 pmcid: 8740189
Ferensztajn-Rochowiak E, Chłopocka-Woźniak M, Rybakowski JK. Ultra-long-term lithium therapy: all-important matters and a case of successful 50-year lithium treatment. Braz J Psychiatry. 2021;43(4):407–13. https://doi.org/10.1590/1516-4446-2020-1111 .
doi: 10.1590/1516-4446-2020-1111 pubmed: 32965432
Fountoulakis KN, Tohen M, Zarate CA Jr. Lithium treatment of Bipolar disorder in adults: a systematic review of randomized trials and meta-analyses. Eur Neuropsychopharmacol. 2022;54:100–15. https://doi.org/10.1016/j.euroneuro.2021.10.003 .
doi: 10.1016/j.euroneuro.2021.10.003 pubmed: 34980362 pmcid: 8808297
Geoffroy PA, Samalin L, Llorca PM, Curis E, Bellivier F. Influence of lithium on sleep and chronotypes in remitted patients with bipolar disorder. J Affect Disord. 2016;204:32–9. https://doi.org/10.1016/j.jad.2016.06.015 .
doi: 10.1016/j.jad.2016.06.015 pubmed: 27318597
Ghasemi M, Dehpour AR. The NMDA receptor/nitric oxide pathway: a target for the therapeutic and toxic effects of lithium. Trends Pharmacol Sci. 2011;32(7):420–34. https://doi.org/10.1016/j.tips.2011.03.006 .
doi: 10.1016/j.tips.2011.03.006 pubmed: 21492946
Håvik B, Le Hellard S, Rietschel M, et al. The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia. Biol Psychiatry. 2011;70(1):35–42. https://doi.org/10.1016/j.biopsych.2011.01.030 .
doi: 10.1016/j.biopsych.2011.01.030 pubmed: 21439553
Herrera-Rivero M, Gutiérrez-Fragoso K; International Consortium on Lithium Genetics (ConLi+Gen), Kurtz J, Baune BT. Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder. Transl Psychiatry. 2024;14(1):174. https://doi.org/10.1038/s41398-024-02865-4
Hou L, Heilbronner U, Degenhardt F, et al. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016;387(10023):1085–93. https://doi.org/10.1016/S0140-6736(16)00143-4 .
doi: 10.1016/S0140-6736(16)00143-4 pubmed: 26806518 pmcid: 4814312
Lambert SA, Gil L, Jupp S, et al. The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation. Nat Genet. 2021;53(4):420–5. https://doi.org/10.1038/s41588-021-00783-5 .
doi: 10.1038/s41588-021-00783-5 pubmed: 33692568
Ma Y, Patil S, Zhou X, Mukherjee B, Fritsche LG. ExPRSweb: an online repository with polygenic risk scores for common health-related exposures. Am J Hum Genet. 2022;109(10):1742–60. https://doi.org/10.1016/j.ajhg.2022.09.001 .
doi: 10.1016/j.ajhg.2022.09.001 pubmed: 36152628 pmcid: 9606385
Manchia M, Adli M, Akula N, et al. Assessment of response to lithium maintenance treatment in bipolar disorder: a consortium on lithium genetics (ConLiGen) report. PLoS ONE. 2013;8(6): e65636. https://doi.org/10.1371/journal.pone.0065636 .
doi: 10.1371/journal.pone.0065636 pubmed: 23840348 pmcid: 3686769
Miller BJ, McCall WV. Insomnia and suicide as reported adverse effects of second-generation antipsychotics and mood stabilizers. J Clin Sleep Med. 2022;18(2):517–22. https://doi.org/10.5664/jcsm.9646 .
doi: 10.5664/jcsm.9646 pubmed: 34543183 pmcid: 8804988
Nunes A, Ardau R, Berghöfer A, et al. Prediction of lithium response using clinical data. Acta Psychiatr Scand. 2020;141(2):131–41. https://doi.org/10.1111/acps.13122 .
doi: 10.1111/acps.13122 pubmed: 31667829
Papiol S, Schulze TG, Heilbronner U. Lithium response in bipolar disorder: Genetics, genomics, and beyond. Neurosci Lett. 2022;785: 136786. https://doi.org/10.1016/j.neulet.2022.136786 .
doi: 10.1016/j.neulet.2022.136786 pubmed: 35817312
Privé F, Aschard H, Carmi S, et al. Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort. Am J Hum Genet. 2022;109(1):12–23. https://doi.org/10.1016/j.ajhg.2021.11.008 .
doi: 10.1016/j.ajhg.2021.11.008 pubmed: 34995502 pmcid: 8764121
Queissner R, Lenger M, Birner A, et al. The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder. J Affect Disord. 2021;281:228–34. https://doi.org/10.1016/j.jad.2020.11.063 .
doi: 10.1016/j.jad.2020.11.063 pubmed: 33338840
Rybakowski JK. Antiviral, immunomodulatory, and neuroprotective effect of lithium. J Integr Neurosci. 2022;21(2):68. https://doi.org/10.31083/j.jin2102068 .
doi: 10.31083/j.jin2102068 pubmed: 35364656
Schubert KO, Thalamuthu A, Amare AT, et al. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients. Transl Psychiatry. 2021;11(1):606. https://doi.org/10.1038/s41398-021-01702-2 .
doi: 10.1038/s41398-021-01702-2 pubmed: 34845190 pmcid: 8630000
Steardo L Jr, de Filippis R, Carbone EA, Segura-Garcia C, Verkhratsky A, De Fazio P. Sleep disturbance in bipolar disorder: neuroglia and circadian rhythms. Front Psychiatry. 2019;10:501. https://doi.org/10.3389/fpsyt.2019.00501 .
doi: 10.3389/fpsyt.2019.00501 pubmed: 31379620 pmcid: 6656854
Sylvia LG, Shelton RC, Kemp DE, et al. Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE). Bipolar Disord. 2015;17(2):212–23. https://doi.org/10.1111/bdi.12243 .
doi: 10.1111/bdi.12243 pubmed: 25130321
Szałach ŁP, Lisowska KA, Cubała WJ, Barbuti M, Perugi G. The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder. Front Neurosci. 2023;17:1213766. https://doi.org/10.3389/fnins.2023.1213766 .
doi: 10.3389/fnins.2023.1213766 pubmed: 37662097 pmcid: 10469704
Tang J, Chen X, Xu X, et al. Significant linkage and association between a functional (GT)n polymorphism in promoter of the N-methyl-D-aspartate receptor subunit gene (GRIN2A) and schizophrenia. Neurosci Lett. 2006;409(1):80–2. https://doi.org/10.1016/j.neulet.2006.09.022 .
doi: 10.1016/j.neulet.2006.09.022 pubmed: 17011703
Tondo L, Baldessarini RJ, Floris G. Long-term clinical effectiveness of lithium maintenance treatment in types I and II bipolar disorders. Br J Psychiatry. 2001;178(Suppl 41):S184–90.
doi: 10.1192/bjp.178.41.s184 pubmed: 11388960
Vijayakumar A, Mahapatra NR. Renalase: a novel regulator of cardiometabolic and renal diseases. Hypertens Res. 2022;45(10):1582–98. https://doi.org/10.1038/s41440-022-00986-1 .
doi: 10.1038/s41440-022-00986-1 pubmed: 35941358 pmcid: 9358379
Volkmann C, Bschor T, Köhler S. Lithium treatment over the lifespan in bipolar disorders. Front Psychiatry. 2020;11:377. https://doi.org/10.3389/fpsyt.2020.00377 .
doi: 10.3389/fpsyt.2020.00377 pubmed: 32457664 pmcid: 7221175
Xu N, Shinohara K, Saunders KEA, Geddes JR, Cipriani A. Effect of lithium on circadian rhythm in bipolar disorder: A systematic review and meta-analysis. Bipolar Disord. 2021;23(5):445–53. https://doi.org/10.1111/bdi.13070 .
doi: 10.1111/bdi.13070 pubmed: 33650218
Yoshida T, Papiol S, Plans L, et al. The polygenic effect of the response to lithium on suicidal behavior. Eur Neuropsychopharmacol. 2019;29:S179. https://doi.org/10.1016/j.euroneuro.2019.08.124 .
doi: 10.1016/j.euroneuro.2019.08.124
Yu Z, Ono C, Aiba S, et al. Therapeutic concentration of lithium stimulates complement C3 production in dendritic cells and microglia via GSK-3 inhibition. Glia. 2015;63(2):257–70. https://doi.org/10.1002/glia.22749 .
doi: 10.1002/glia.22749 pubmed: 25179772

Auteurs

Marisol Herrera-Rivero (M)

Department of Psychiatry, University of Münster and Joint Institute for Individualisation in a Changing Environment (JICE), University of Münster and Bielefeld University, Albert-Schweitzer-Campus 1, Building A9, 48149, Münster, Germany.

Mazda Adli (M)

Department of Psychiatry and Psychotherapy, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.
Fliedner Klinik Berlin, Berlin, Germany.

Kazufumi Akiyama (K)

Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Mibu, Japan.

Nirmala Akula (N)

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Baltimore, USA.

Azmeraw T Amare (AT)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.

Raffaella Ardau (R)

Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.

Bárbara Arias (B)

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, Barcelona, Spain.

Jean-Michel Aubry (JM)

Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals, Geneva, Switzerland.
Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Lena Backlund (L)

Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Frank Bellivier (F)

Département de Psychiatrie et de Médecine Addictologique, INSERM UMR-S 1144, Université Paris Cité, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière, F. Widal, Paris, France.

Antonio Benabarre (A)

Bipolar Disorder Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

Susanne Bengesser (S)

Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.

Abesh Kumar Bhattacharjee (AK)

Department of Psychiatry, University of California San Diego, San Diego, USA.

Joanna M Biernacka (JM)

Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, USA.

Armin Birner (A)

Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.

Micah Cearns (M)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.

Pablo Cervantes (P)

The Neuromodulation Unit, McGill University Health Centre, Montreal, Canada.

Hsi-Chung Chen (HC)

Department of Psychiatry & Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan.

Caterina Chillotti (C)

Unit of Clinical Pharmacology, Hospital University Agency of Cagliari, Cagliari, Italy.

Sven Cichon (S)

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 (INM-1), Research Center Jülich, Jülich, Germany.

Scott R Clark (SR)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.

Francesc Colom (F)

Mental Health Research Group, IMIM-Hospital del Mar, Barcelona, Spain.
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.

Cristiana Cruceanu (C)

Douglas Mental Health University Institute, McGill University, Montreal, Canada.

Piotr M Czerski (PM)

Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznań, Poland.

Nina Dalkner (N)

Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.

Franziska Degenhardt (F)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Maria Del Zompo (M)

Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

J Raymond DePaulo (JR)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.

Bruno Etain (B)

Département de Psychiatrie et de Médecine Addictologique, INSERM UMR-S 1144, Université Paris Cité, AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière, F. Widal, Paris, France.

Peter Falkai (P)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.

Ewa Ferensztajn-Rochowiak (E)

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.

Andreas J Forstner (AJ)

Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany.
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Josef Frank (J)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Louise Frisén (L)

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Mark A Frye (MA)

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, USA.

Janice M Fullerton (JM)

Neuroscience Research, Australia and School of Biomedical Sciences, University of New South Wales, Sydney, Australia.

Carla Gallo (C)

Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, San Martín de Porres, Peru.

Sébastien Gard (S)

Service de Psychiatrie, Hôpital Charles Perrens, Bordeaux, France.

Julie S Garnham (JS)

Department of Psychiatry, Dalhousie University, Halifax, Canada.

Fernando S Goes (FS)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.

Maria Grigoroiu-Serbanescu (M)

Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania.

Paul Grof (P)

Mood Disorders Center of Ottawa, Ottawa, Canada.

Ryota Hashimoto (R)

Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Roland Hasler (R)

Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals, Geneva, Switzerland.

Joanna Hauser (J)

Psychiatric Genetic Unit, Poznan University of Medical Sciences, Poznań, Poland.

Urs Heilbronner (U)

Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.

Stefan Herms (S)

Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Per Hoffmann (P)

Human Genomics Research Group, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Liping Hou (L)

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Baltimore, USA.

Yi-Hsiang Hsu (YH)

Program for Quantitative Genomics, Harvard School of Public Health and HSL Institute for Aging Research, Harvard Medical School, Boston, USA.

Stephane Jamain (S)

Univ. Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, Fondation FondaMental, Créteil, France.

Esther Jiménez (E)

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII, Barcelona, Spain.

Jean-Pierre Kahn (JP)

Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université, Nancy, France.

Layla Kassem (L)

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Baltimore, USA.

Tadafumi Kato (T)

Department of Psychiatry & Behavioral Science, Graduate School of Medicine, Juntendo University, Tokyo, Japan.

John Kelsoe (J)

Department of Psychiatry, University of California San Diego, San Diego, USA.

Sarah Kittel-Schneider (S)

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.

Po-Hsiu Kuo (PH)

Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Ichiro Kusumi (I)

Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Barbara König (B)

Department of Psychiatry and Psychotherapeutic Medicine, Landesklinikum Neunkirchen, Neunkirchen, Austria.

Gonzalo Laje (G)

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Baltimore, USA.

Mikael Landén (M)

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 (C)

Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Marion Leboyer (M)

Univ. Paris Est Créteil, INSERM, IMRB, Translational Neuropsychiatry, AP-HP, Mondor University Hospital, DMU Impact, Fondation FondaMental, Créteil, France.

Susan G Leckband (SG)

Office of Mental Health, VA San Diego Healthcare System, California, USA.

Mario Maj (M)

Department of Psychiatry, University of Campania 'Luigi Vanvitelli', Caserta, Italy.

Mirko Manchia (M)

Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Department of Pharmacology, Dalhousie University, Halifax, Canada.

Cynthia Marie-Claire (C)

Université Paris Cité, Inserm UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie, 75006, Paris, France.

Lina Martinsson (L)

Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.

Michael J McCarthy (MJ)

Department of Psychiatry, University of California San Diego, San Diego, USA.
Department of Psychiatry, VA San Diego Healthcare System, San Diego, CA, USA.

Susan L McElroy (SL)

Department of Psychiatry, Lindner Center of Hope/University of Cincinnati, Cincinnati, USA.

Vincent Millischer (V)

Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.

Marina Mitjans (M)

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Department of Genetics, Microbiology and Statistics, Faculty of Biology, Institut de Biomedicina de La Universitat de Barcelona (IBUB), University of Barcelona, Barcelona, Spain.

Francis M Mondimore (FM)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.

Palmiero Monteleone (P)

Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi, Italy.

Caroline M Nievergelt (CM)

Department of Psychiatry, University of California San Diego, San Diego, USA.

Tomas Novák (T)

National Institute of Mental Health, Klecany, Czech Republic.

Markus M Nöthen (MM)

Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.

Claire O'Donovan (C)

Department of Psychiatry, Dalhousie University, Halifax, Canada.

Norio Ozaki (N)

Department of Psychiatry & Department of Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Sergi Papiol (S)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.

Andrea Pfennig (A)

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.

Claudia Pisanu (C)

Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

James B Potash (JB)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.

Andreas Reif (A)

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.

Eva Reininghaus (E)

Department of Psychiatry and Psychotherapeutic Medicine, Research Unit for Bipolar Affective Disorder, Medical University of Graz, Graz, Austria.

Hélène Richard-Lepouriel (H)

Department of Psychiatry, Division of Psychiatric Specialities, Geneva University Hospitals, Geneva, Switzerland.
Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Gloria Roberts (G)

School of Psychiatry, University of New South Wales, Sydney, Australia.

Guy A Rouleau (GA)

Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

Janusz K Rybakowski (JK)

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznań, Poland.

Martin Schalling (M)

Department of Molecular Medicine and Surgery and Center for Molecular Medicine at Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Peter R Schofield (PR)

Neuroscience Research, Australia and School of Biomedical Sciences, University of New South Wales, Sydney, Australia.

Klaus Oliver Schubert (KO)

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia.
Northern Adelaide Local Health Network, Mental Health Services, Adelaide, Australia.

Eva C Schulte (EC)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Munich, Germany.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
Department of Psychiatry and Psychotherapy, University Hospital Bonn, Medical Faculty University of Bonn, Bonn, Germany.

Barbara W Schweizer (BW)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.

Giovanni Severino (G)

Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

Tatyana Shekhtman (T)

Department of Psychiatry, University of California San Diego, San Diego, USA.

Paul D Shilling (PD)

Department of Psychiatry, University of California San Diego, San Diego, USA.

Katzutaka Shimoda (K)

Department of Psychiatry, Dokkyo Medical University School of Medicine, Mibu, Japan.

Christian Simhandl (C)

Medical Faculty, Bipolar Center Wiener Neustadt, Sigmund Freud University, Vienna, Austria.

Claire M Slaney (CM)

Department of Psychiatry, Dalhousie University, Halifax, Canada.

Alessio Squassina (A)

Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

Thomas Stamm (T)

Department of Psychiatry and Psychotherapy, Charité, Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.

Pavla Stopkova (P)

National Institute of Mental Health, Klecany, Czech Republic.

Fabian Streit (F)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Fasil Tekola-Ayele (F)

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA.

Anbupalam Thalamuthu (A)

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, Australia.

Alfonso Tortorella (A)

Department of Psychiatry, University of Perugia, Perugia, Italy.

Gustavo Turecki (G)

Douglas Mental Health University Institute, McGill University, Montreal, Canada.

Julia Veeh (J)

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt, Germany.

Eduard Vieta (E)

Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, ISCIII, Barcelona, Spain.

Biju Viswanath (B)

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.

Stephanie H Witt (SH)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Peter P Zandi (PP)

Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.

Martin Alda (M)

Department of Psychiatry, Dalhousie University, Halifax, Canada.

Michael Bauer (M)

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.

Francis J McMahon (FJ)

Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Baltimore, USA.

Philip B Mitchell (PB)

School of Psychiatry, University of New South Wales, Sydney, Australia.

Marcella Rietschel (M)

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Thomas G Schulze (TG)

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, USA.
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
Department of Psychiatry and Behavioral Sciences, Norton College of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.

Bernhard T Baune (BT)

Department of Psychiatry, University of Münster and Joint Institute for Individualisation in a Changing Environment (JICE), University of Münster and Bielefeld University, Albert-Schweitzer-Campus 1, Building A9, 48149, Münster, Germany. Bernhard.Baune@ukmuenster.de.
Department of Psychiatry, Melbourne Medical School, University of Melbourne and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Australia. Bernhard.Baune@ukmuenster.de.

Classifications MeSH