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Neuropsychobiology 2010;62:72–78

The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment

Schulze T.G.a, g,ε · Alda M.m, ε · Adli M.h, ε · Akula N.a · Ardau R.t · Bui E.T.a · Chillotti C.t · Cichon S.i, ζ · Czerski P.v · Del Zompo M.t, u · Detera-Wadleigh S.D.a · Grof P.n, o, ε · Gruber O.j · Hashimoto R.x, δ · Hauser J.v · Hoban R.b, c · Iwata N.y, δ · Kassem L.a · Kato T.z, δ · Kittel-Schneider S.k · Kliwicki S.w · Kelsoe J.R.b, c · Kusumi I.β, δ · Laje G.a · Leckband S.G.b, d, e · Manchia M.u · MacQueen G.p · Masui T.β, δ · Ozaki N.γ, δ · Perlis R.H.f · Pfennig A.l, ε · Piccardi P.u · Richardson S.a · Rouleau G.q · Reif A.k · Rybakowski J.K.w, ε · Sasse J.l, ε · Schumacher J.a, i · Severino G.u · Smoller J.W.f · Squassina A.u · Turecki G.r · Young L.T.s, ε · Yoshikawa T.α, δ · Bauer M.l, ε · McMahon F.J.a
aGenetic Basis of Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Md., bDepartment of Psychiatry, University of California San Diego, cDepartment of Psychiatry, VA San Diego Healthcare System, and dDepartment of Pharmacy, VA San Diego Healthcare System, La Jolla, Calif., eSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, Calif., and fDepartment of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Mass., USA; gDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, hDepartment of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, iDepartment of Genomics, Life and Brain Center and Institute of Human Genetics, University of Bonn, Bonn, jDepartment of Psychiatry and Psychotherapy, Georg-August University, Göttingen, kDepartment of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, and lDepartment of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; mDepartment of Psychiatry, Dalhousie University, Halifax, N.S., nMood Disorders Center of Ottawa, Ottawa, Ont., oDepartment of Psychiatry, University of Toronto, Toronto, Ont., pDepartment of Psychiatry, University of Calgary, Calgary, Alta., qCHU Sainte-Justine Research Center, Department of Medicine, University of Montreal, and rDepartment of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Que., and sDepartment of Psychiatry, University of British Columbia, Vancouver, B.C., Canada; tUnit of Clinical Pharmacology, Hospital University Agency, and uDepartment of Neuroscience ‘B.B. Brodie’, University of Cagliari, Cagliari, Italy; vPsychiatric Genetic Unit, and wDepartment of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland; wOsaka University Graduate School of Medicine, Osaka,yDepartment of Psychiatry, Fujita Health University School of Medicine, Toyoake,zLaboratory for Molecular Dynamics of Mental Disorders, andαLaboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama,βDepartment of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo,γDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan;δThe Japanese Collaborative Group on the Genetics of Lithium Response in Bipolar Disorder;εThe International Group for the Study of Lithium-Treated Patients (IGSLI);ζInstitute of Neurosciences and Medicine (INM-1), Research Center Juelich, Juelich, Germany
email Corresponding Author

 goto top of outline Key Words

  • Manic-depressive illness
  • Schizoaffective disorder
  • Mood stabilizer
  • Antidepressants
  • Suicidal behavior
  • Genome-wide association study
  • Neurogenesis
  • Neuroplasticity

 goto top of outline Abstract

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients ( and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics ( to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts.

Copyright © 2010 S. Karger AG, Basel

 goto top of outline References
  1. Swen JJ, Huizinga TW, Gelderblom H, de Vries EG, Assendelft WJ, Kirchheiner J, Guchelaar HJ: Translating pharmacogenomics: challenges on the road to the clinic. PLoS Med 2007;4:e209.
  2. Wadelius M, Sörlin K, Wallerman O, Karlsson J, Yue QY, Magnusson PK, Wadelius C, Melhus H: Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J 2004;4:40–48.
  3. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT: Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486.
  4. Penny MA, McHale D: Pharmacogenomics and the drug discovery pipeline: when should it be implemented? Am J Pharmacogenomics 2005;5:53–62.
  5. Roses AD: Pharmacogenetics in drug discovery and development: a translational perspective. Nat Rev Drug Discov 2008;7:807–817.
  6. Fava M, Rush AJ, Trivedi MH, Nierenberg AA, Thase ME, Sackeim HA, Quitkin FM, Wisniewski S, Lavori PW, Rosenbaum JF, Kupfer DJ: Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study. Psychiatr Clin North Am 2003;26:457–494.
  7. Uher R, Farmer A, Maier W, Rietschel M, Hauser J, Marusic A, Mors O, Elkin A, Williamson RJ, Schmael C, Henigsberg N, Perez J, Mendlewicz J, Janzing JG, Zobel A, Skibinska M, Kozel D, Stamp AS, Bajs M, Placentino A, Barreto M, McGuffin P, Aitchison KJ: Measuring depression: comparison and integration of three scales in the GENDEP study. Psychol Med 2008;38:289–300.
  8. McMahon FJ, Buervenich S, Charney D, Lipsky R, Rush AJ, Wilson AF, Sorant AJ, Papanicolaou GJ, Laje G, Fava M, Trivedi MH, Wisniewski SR, Manji H: Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 2006;78:804–814.
  9. Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ: Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry 2007;164:1530–1538.
  10. Perlis RH, Purcell S, Fava M, Fagerness J, Rush AJ, Trivedi MH, Smoller JW: Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry 2007;64:689–697.
  11. Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, Lipsky R, Wisniewski SR, Manji H, McMahon FJ: Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry 2007;164:1181–1188.
  12. Perlis RH, Moorjani P, Fagerness J, Purcell S, Trivedi MH, Fava M, Rush AJ, Smoller JW: Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study. Neuropsychopharmacology 2008;33:2810–2819.
  13. Lekman M, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, Lipsky R, Wisniewski SR, Manji H, McMahon FJ, Paddock S: The FKBP5-gene in depression and treatment response – an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry 2008;63:1103–1110.
  14. Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, Barreto M, Placentino A, Dernovsek MZ, Schulze TG, Kalember P, Zobel A, Czerski PM, Larsen ER, Sourey D, Giovannini C, Gray JM, Lewis CM, Farmer A, Aitchison KJ, McGuffin P, Craig I: Genetic predictors of response to antidepressants in the GENDEP project. Pharmacogenomics J 2009;9:225–233.
  15. Bauer M, Grof P, Müller-Oerlinghausen B (eds): Lithium in Neuropsychiatry: The Comprehensive Guide. London, Informa Healthcare, 2006.
  16. Perlis RH, Smoller JW, Ferreira MAR, McQuillin A, Bass N, Chir MB, Lawrence J, Sachs GS, Nimgaonkar V, Scolnick EM, Gurling H, Sklar P, Purcell S: A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder. Am J Psychiatry 2009;166:718–725.
  17. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nöthen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Höfels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, McMahon FJ: A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 2008;13:197–207.
  18. Rietschel M, Kennedy JL, Macciardi F, Meltzer HY: Application of pharmacogenetics to psychotic disorders: the first consensus conference. The Consensus Group for Outcome Measures in Psychoses for Pharmacological Studies. Schizophr Res 1999;37:191–196.
  19. Lerer B, Segman RH, Fangerau H, Daly AK, Basile VS, Cavallaro R, Aschauer HN, McCreadie RG, Ohlraun S, Ferrier N, Masellis M, Verga M, Scharfetter J, Rietschel M, Lovlie R, Levy UH, Meltzer HY, Kennedy JL, Steen VM, Macciardi F: Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacology 2002;27:105–119.
  20. Malhotra AK, Murphy GM Jr, Kennedy JL: Pharmacogenetics of psychotropic drug response. Am J Psychiatry 2004;161:780–796.
  21. Correll CU, Malhotra AK: Pharmacogenetics of antipsychotic-induced weight gain. Psychopharmacology (Berl) 2004:477–489.
  22. Malhotra AK, Lencz T, Correll CU, Kane JM: Genomics and the future of pharmacotherapy in psychiatry. Int Rev Psychiatry 2007;19:523–530.
  23. van den Oord EJ, Adkins DE, McClay J, Lieberman J, Sullivan PF: A systematic method for estimating individual responses to treatment with antipsychotics in CATIE. Schizophr Res 2009;107:13–21.
  24. Need AC, Keefe RS, Ge D, Grossman I, Dickson S, McEvoy JP, Goldstein DB: Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. Eur J Hum Genet 2009;17:946–957.
  25. Grof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M, O’Donovan C, Alda M: Is response to prophylactic lithium a familial trait? J Clin Psychiatry 2002;63:942–947.
  26. Perlis RH, Ostacher MJ, Patel JK, Marangell LB, Zhang H, Wisniewski SR, Ketter TA, Miklowitz DJ, Otto MW, Gyulai L, Reilly-Harrington NA, Nierenberg AA, Sachs GS, Thase ME: Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry 2006;163:217–224.
  27. Garnham J, Munro A, Slaney C, Macdougall M, Passmore M, Duffy A, O’Donovan C, Teehan A, Alda M: Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study. J Affect Disord 2007;104:185–190.
  28. Passmore MJ, Garnham J, Duffy A, MacDougall M, Munro A, Slaney C, Teehan A, Alda M: Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine. Bipolar Disord 2003;5:110–114.
  29. Hajek T, Hahn M, Slaney C, Garnham J, Green J, Ruzickova M, Zvolsky P, Alda M: Rapid cycling bipolar disorders in primary and tertiary-care treated patients. Bipolar Disord 2008;10:495–502.
  30. Purcell S, Cherny SS, Sham PC: Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003;19:149–150.

 goto top of outline Author Contacts

Thomas G. Schulze, MD, Unit on the Genetic Basis of Mood and Anxiety Disorders
National Institute of Mental Health (NIMH), National Institutes of Health (NIH)
35 Convent Drive, Bldg. 35, Rm 1A205, MSC 3719
Bethesda, MD 20892-3719 (USA)
Tel. +1 301 451 7213, Fax +1 301 402 9081, E-Mail

 goto top of outline Article Information

Published online: May 8, 2010
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 0, Number of References : 30

 goto top of outline Publication Details

Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)

Vol. 62, No. 1, Year 2010 (Cover Date: June 2010)

Journal Editor: Strik W. (Bern)
ISSN: 0302-282X (Print), eISSN: 1423-0224 (Online)

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