Update on research into the genetics and pharmacogenetics of bipolar disorder
Thomas G. Schulze, Selen Ozkan
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Article No: 0   Article Type :  Guest Editorial
Bipolar disorder (BD) is a severe mental disorder that is characterized by recurrent episodes of mania, and depression. The phenotypic expression can be complemented by suicidal behavior, psychosis, comorbid anxiety, substance abuse, and rapid cycling (1). With a prevalence of ~1% and high risk of morbidity, it is a major health problem (2). BD has been shown to be a highly heritable disease, with concordance rates being ~85% within twin studies (3). As in other psychiatric disorders, polygenic components have a role in the liability of the disorder. The combination of both genetic and environmental effects influence the risk of developing the disorder. Up to date, there have been several studies of BD including linkage analysis, candidate gene studies, and genomewide association studies (GWAS). Moreover, it has been established that there is a genetic correlation between BD and schizophrenia conferred by common genetic variation, so called single nucleotide polymorphisms (SNPs), suggesting a shared genetic etiology between these diagnostic entities (4). Yet, our knowledge of the role of genetic factors in susceptibility of BD is still limited. Given the fact that BD is a highly heterogeneous disorder, studies with more homogenized groups that gather samples with more specific properties, such as subphenotypes of BD or patients positively responsive to specific drug treatments, may help improve the efficiency of studies...
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Dusunen Adam The Journal of Psychiatry and Neurological Sciences 2017;30:165-169
REFERENCES
1.Cruceanu C, Ambalavanan A, Spiegelman D, Gauthier J, Lafrenière RG, Dion PA, Alda M, Turecki G, Rouleau GA. Family-based exome-sequencing approach identifies rare susceptibility variants for lithium-responsive bipolar disorder. Genome 2013; 56:634-640.

2.Kawakami N. Large scale epidemiology study of the prevalence of mental disorders: World Mental Health Japan Survey Second. A report of the Health Labour Sciences Research Grant from The Ministry of Health Labour and Welfare (H25-Seishin-Ippan-006), Tokyo, 2014.

3.McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 2003; 60:497-502.

4.Shinozaki G, Potash JB. New developments in the genetics of bipolar disorder. Curr Psychiatry Rep 2014; 16:493.

5.Budde M, Degner D, Brockmöller J, Schulze TG. Pharmacogenomic aspects of bipolar disorder: An update. Eur Neuropsychopharmacol 2017; 27:599-609.

6.Budde M, Forstner AJ, Adorjan K, Schaupp SK, Nöthen MM, Schulze TG. Genetics of bipolar disorder. Nervenarzt 2017; 88:755-759.

7.Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447:661-678.

8.Cruceanu C, Alda M, Rouleau G, Turecki G. Response to treatment in bipolar disorder. Curr Opin Psychiatry 2011; 24:24-28.

9.Pisanu C, Melis C, Squassina A. Lithium pharmacogenetics: where do we stand? Drug Dev Res 2016; 77:368-373.

10.Atack JR. Inositol monophosphatase inhibitors–lithium mimetics? Med Res Rev 1997; 17:215-224.

11.Cruceanu C, Alda M, Turecki G. Lithium: a key to the genetics of bipolar disorder. Genome Med 2009; 1:79.

12.Perlis RH, Smoller JW, Ferreira MA, McQuillin A, Bass N, 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.

13.Squassina A, Manchia M, Borg J, Congiu D, Costa M, Georgitsi M, Chillotti C, Ardau R, Mitropoulos K, Severino G, Del Zompo M, Patrinos GP. Evidence for association of an ACCN1 gene variant with response to lithium treatment in Sardinian patients with bipolar disorder. Pharmacogenomics 2011; 12:1559-1569.

14.Chen CH, Lee CS, Lee MT, Ouyang WC, Chen CC, Chong MY, Wu JY, Tan HK, Lee YC, Chuo LJ, Chiu NY, Tsang HY, Chang TJ, Lung FW, Chiu CH, Chang CH, Chen YS, Hou YM, Chen CC, Lai TJ, Tung CL, Chen CY, Lane HY, Su TP, Feng J, Lin JJ, Chang CJ, Teng PR, Liu CY, Chen CK, Liu IC, Chen JJ, Lu T, Fan CC, Wu CK, Li CF, Wang KH, Wu LS, Peng HL, Chang CP, Lu LS, Chen YT, Cheng AT; Taiwan Bipolar Consortium. Variant GADL1 and response to lithium therapy in bipolar I disorder. N Engl J Med 2014; 370:119-128.

15.Weng JTY, Chi YX, Wu LH, Lee CS, Cheng ATA. MicroRNA and gene expression profiling of response to lithium treatment for bipolar I disorder. Biomedical Engineering and Informatics (BMEI), 2015 8th International Conference on. IEEE, 2015.

16.Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Backlund L, Banzato CEM, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Brichant-Petitjean C, Bui ET, Cervantes P, Chen GB, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cousins DA, Cruceanu C, Czerski PM, Dantas CR, Dayer A, Étain B, Falkai P, Forstner AJ, Frisén L, Fullerton JM, Gard S, Garnham JS, Goes FS, Grof P, Gruber O, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kittel-Schneider S, Kliwicki S, König B, Kusumi I, Lackner N, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Jaramillo CAL, MacQueen G, Manchia M, Martinsson L, Mattheisen M, McCarthy MJ, McElroy SL, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Ösby U, Ozaki N, Perlis RH, Pfennig A, Reich-Erkelenz D, Rouleau GA, Schofield PR, Schubert KO, Schweizer BW, Seemüller F, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Smoller JW, Squassina A, Stamm T, Stopkova P, Tighe SK, Tortorella A, Turecki G, Volkert J, Witt S, Wright A, Young LT, Zandi PP, Potash JB, DePaulo JR, Bauer M, Reininghaus EZ, Novák T, Aubry JM, Maj M, Baune BT, Mitchell PB, Vieta E, Frye MA, Rybakowski JK, Kuo PH, Kato T, Grigoroiu-Serbanescu M, Reif A, Del Zompo M, Bellivier F, Schalling M, Wray NR, Kelsoe JR, Alda M, Rietschel M, McMahon FJ, Schulze TG. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet 2016; 387:1085-1093.

17.Bauer M, Gitlin M. What Is Lithium and How Does It Work? The Essential Guide to Lithium Treatment. Springer International Publishing, 2016, p. 33-43.

18.Biesecker BB, Peay HL. Genomic sequencing for psychiatric disorders: promise and challenge. Int J Neuropsychopharmacol 2013; 16:1667-1672.

19.Kato T. Whole genome/exome sequencing in mood and psychotic disorders. Psychiatry Clin Neurosci 2015; 69:65-76.

20.Chen YC, Carter H, Parla J, Kramer M, Goes FS, Pirooznia M, Zandi PP, McCombie WR, Potash JB, Karchin R. A hybrid likelihood model for sequence-based disease association studies. PLoS Genet 2013; 9:e1003224.

21.Ament SA, Szelinger S, Glusman G, Ashworth J, Hou L, Akula N, Shekhtman T, Badner JA, Brunkow ME, Mauldin DE, Stittrich AB, Rouleau K, Detera-Wadleigh SD, Nurnberger JI Jr, Edenberg HJ, Gershon ES, Schork N; Bipolar Genome Study, Price ND, Gelinas R, Hood L, Craig D, McMahon FJ, Kelsoe JR, Roach JC. Rare variants in neuronal excitability genes influence risk for bipolar disorder. Proc Natl Acad Sci USA 2015; 112: 3576-3581.

22.Malhotra D, McCarthy S, Michaelson JJ, Vacic V, Burdick KE, Yoon S, Cichon S, Corvin A, Gary S, Gershon ES, Gill M, Karayiorgou M, Kelsoe JR, Krastoshevsky O, Krause V, Leibenluft E, Levy DL, Makarov V, Bhandari A, Malhotra AK, McMahon FJ, Nöthen MM, Potash JB, Rietschel M, Schulze TG, Sebat J. High frequencies of de novo CNVs in bipolar disorder and schizophrenia. Neuron 2011; 72:951-963.

23.Georgieva L, Rees E, Moran JL, Chambert KD, Milanova V, Craddock N, Purcell S, Sklar P, McCarroll S, Holmans P, O’Donovan MC, Owen MJ, Kirov G. De novo CNVs in bipolar affective disorder and schizophrenia. Hum Mol Genet 2014; 23:6677-6683.

24.Neale BM, Kou Y, Liu L, Ma’ayan A, Samocha KE, Sabo A, Lin CF, Stevens C, Wang LS, Makarov V, Polak P, Yoon S, Maguire J, Crawford EL, Campbell NG, Geller ET, Valladares O, Schafer C, Liu H, Zhao T, Cai G, Lihm J, Dannenfelser R, Jabado O, Peralta Z, Nagaswamy U, Muzny D, Reid JG, Newsham I, Wu Y, Lewis L, Han Y, Voight BF, Lim E, Rossin E, Kirby A, Flannick J, Fromer M, Shakir K, Fennell T, Garimella K, Banks E, Poplin R, Gabriel S, DePristo M, Wimbish JR, Boone BE, Levy SE, Betancur C, Sunyaev S, Boerwinkle E, Buxbaum JD, Cook EH Jr, Devlin B, Gibbs RA, Roeder K, Schellenberg GD, Sutcliffe JS, Daly MJ. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012; 485:242-245.

25.De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma’ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK; DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 2014; 515:209-215.

26.Georgi B, Craig D, Kember RL, Liu W, Lindquist I, Nasser S, Brown C, Egeland JA, Paul SM, Bućan M. Genomic view of bipolar disorder revealed by whole genome sequencing in a genetic isolate. PLoS Genet 2014; 10:e1004229.

27.Fiorentino A, O’Brien NL, Locke DP, McQuillin A, Jarram A, Anjorin A, Kandaswamy R, Curtis D, Blizard RA, Gurling HM. Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data. Bipolar Disord 2014; 16:583-591.
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