Targeting the schizophrenia genome: A fast track strategy from GWAS to clinic

Molecular Psychiatry

Volumn 20, Issue 7, 2015, Pages 820-826

  Lencz, T ^a,b,c   Malhotra, A K ^a,b,c  

^a ZUCKER HILLSIDE HOSPITAL   (United States)

^b FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

^c DONALD AND BARBARA ZUCKER SCHOOL OF MEDICINE AT HOFSTRA NORTHWELL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; DRUG INDICATION; DRUG MECHANISM; DRUG TARGETING; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; HUMAN; PRIORITY JOURNAL; SCHIZOPHRENIA; ASIAN CONTINENTAL ANCESTRY GROUP; CAUCASIAN; CLINICAL TRIAL (TOPIC); DRUG DATABASE; GENETIC DATABASE; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; PHARMACOGENETICS; PROCEDURES;

NEUROLEPTIC AGENT;

ANTIPSYCHOTIC AGENTS; ASIAN CONTINENTAL ANCESTRY GROUP; CLINICAL TRIALS AS TOPIC; DATABASES, GENETIC; DATABASES, PHARMACEUTICAL; EUROPEAN CONTINENTAL ANCESTRY GROUP; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; PHARMACOGENETICS; SCHIZOPHRENIA;

EID: 84932199315     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2015.28     Document Type: Article

References (66)

1. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-Associated genetic loci. Nature 2014; 511: 421-427
2. Plenge RM, Scolnick EM, Altshuler D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov 2013; 12: 581-594
3. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008; 40: 189-197
4. Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res 1992; 33: 1569-1582
5. Okada Y. From the era of genome analysis to the era of genomic drug discovery: a pioneering example of rheumatoid arthritis. Clin Genet 2014; 86: 432-440
6. Kapur S, Mamo D. Half a century of antipsychotics and still a central role for dopamine D2 receptors. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1081-1090
7. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46: 3-26
8. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov 2002; 1: 727-730
9. Russ AP, Lampel S. The druggable genome: an update. Drug Discov Today 2005; 10: 1607-1610
10. Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC, et al. DGIdb: mining the druggable genome. Nat Methods 2013; 10: 1209-1210
11. Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 2012; 11: 191-200
12. Sanseau P, Agarwal P, Barnes MR, Pastinen T, Richards JB, Cardon LR, Mooser V. Use of genome-wide association studies for drug repositioning. Nat Biotechnol 2012; 30: 317-320
13. Institute of Medicine. Drug Repurposing and Repositioning: Workshop Summary. The National Academies Press: Washington DC, USA, 2014
14. Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3: 673-683
15. Collins FS. Reengineering translational science: the time is right. Sci Transl Med 2011; 3: 90cm17
16. Insel TR. Next-generation treatments for mental disorders. Sci Transl Med 2012; 4: 155ps19
17. Jin G, Wong ST. Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov Today 2014; 19: 637-644
18. Bumb JM, Enning F, Leweke FM. Repurposed drugs for the treatment of schizophrenia and bipolar disorders. Curr Top Med Chem 2013; 13: 2364-2385
19. Rask-Andersen M, Masuram S, Schiöth HB. The druggable genome: evaluation of drug targets in clinical trials suggests major shifts in molecular class and indication. Annu Rev Pharmacol Toxicol 2014; 54: 9-26
20. Law V, Knox C, Djoumbou Y, Jewison T, Guo AC, Liu Y, et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Res 2014; 42: D1091-D1097
21. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 2012; 22: 1760-1774
22. Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 2007; 13: 1102-1107
23. Kinon BJ, Zhang L, Millen BA, Osuntokun OO, Williams JE, Kollack-Walker S, et al A multicenter, inpatient, phase 2, double-blind, placebo-controlled dose-ranging study of LY2140023 monohydrate in patients with DSM-IV schizophrenia. J Clin Psychopharmacol 2011; 31: 349-355
24. Stauffer VL, Millen BA, Andersen S, Kinon BJ, Lagrandeur L, Lindenmayer JP, et al. Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo. Schizophr Res 2013; 150: 434-441
25. Adams DH, Zhang L, Millen BA, Kinon BJ, Gomez JC. Pomaglumetad methionil (LY2140023 monohydrate) and aripiprazole in patients with schizophrenia: a phase 3, multicenter, double-blind comparison. Schizophr Res Treatment 2014; 2014: 758212
26. Hajjar RJ, Zsebo K, Deckelbaum L, Thompson C, Rudy J, Yaroshinsky A, et al. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 2008; 14: 355-367
27. Clamp A, Jayson GC. The clinical development of the bryostatins. Anticancer Drugs 2002; 13: 673-683
28. Sun MK, Alkon DL. Bryostatin-1: pharmacology and therapeutic potential as a CNS drug. CNS Drug Rev 2006; 12: 1-8
29. Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, et al. The NHGRI GWAS Catalog, a curated resource of SNP-Trait associations. Nucleic Acids Res 2014; 42: D1001-D1006
30. Manolio TA. Bringing genome-wide association findings into clinical use. Nat Rev Genet 2013; 14: 549-558
31. Triggle DJ. L-Type calcium channels. Curr Pharm Des 2006; 12: 443-457
32. Hollister LE, Trevino ES. Calcium channel blockers in psychiatric disorders: a review of the literature. Can J Psychiatry 1999; 44: 658-664
33. Gitlin M. Treatment-resistant bipolar disorder. Mol Psychiatry 2006; 11: 227-240
34. Casamassima F, Hay AC, Benedetti A, Lattanzi L, Cassano GB, Perlis RH. L-Type calcium channels and psychiatric disorders: a brief review. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 1373-1390
35. Gershon ES, Grennan K, Busnello J, Badner JA, Ovsiew F, Memon S, et al A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-Associated common SNP of CACNA1C in brain. Mol Psychiatry 2014; 19: 890-894
36. Lee KS, Lee EW. Ionic mechanism of ibutilide in human atrium: evidence for a drug-induced Na+ current through a nifedipine inhibited inward channel. J Pharmacol Exp Ther 1998; 286: 9-22
37. Wood MA, Gilligan DM, Brown-Mahoney C, Nematzadeh F, Stambler BS, Ellenbogen KA. Clinical and electrophysiologic effects of calcium channel blockers in patients receiving ibutilide. Am Heart J 2002; 143: 176-180
38. Yoshimizu T, Pan JQ, Mungenast AE, Madison JM, Su S, Ketterman J, et al. Functional implications of a psychiatric risk variant within CACNA1C in induced human neurons. Mol Psychiatry 2015; 20: 162-169
39. McElroy SL, Winstanley E, Mori N, Martens B, McCoy J, Moeller D, et al A randomized, placebo-controlled study of zonisamide to prevent olanzapine-Associated weight gain. J Clin Psychopharmacol 2012; 32: 165-172
40. Egan MF, Zhao X, Smith A, Troyer MD, Uebele VN, Pidkorytov V, et al. Randomized controlled study of the T-Type calcium channel antagonist MK-8998 for the treatment of acute psychosis in patients with schizophrenia. Hum Psychopharmacol 2013; 28: 124-133
41. de Bartolomeis A, Sarappa C, Magara S, Iasevoli F. Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia. Eur J Pharmacol 2012; 682: 1-11
42. Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 2007; 164: 1593-1602
43. Weiser M, Heresco-Levy U, Davidson M, Javitt DC, Werbeloff N, Gershon AA, et al A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry 2012; 73: e728-e734
44. Singh SP, Singh V. Meta-Analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs 2011; 25: 859-885
45. Umbricht D, Alberati D, Martin-Facklam M, Borroni E, Youssef EA, Ostland M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry 2014; 71: 637-646
46. Rezaei F, Mohammad-Karimi M, Seddighi S, Modabbernia A, Ashrafi M, Salehi B, et al. Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized, double-blind, placebocontrolled study. J Clin Psychopharmacol 2013; 33: 336-342
47. de Lucena D, Fernandes BS, Berk M, Dodd S, Medeiros DW, Pedrini M, et al. Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine. J Clin Psychiatry 2009; 70: 1416-1423
48. Lieberman JA, Papadakis K, Csernansky J, Litman R, Volavka J, Jia XD, et al. MEMMD-29 Study Group A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia. Neuropsychopharmacology 2009; 34: 1322-1329
49. Barkus C, Sanderson DJ, Rawlins JN, Walton ME, Harrison PJ, Bannerman DM. What causes aberrant salience in schizophrenia? A role for impaired short-Term habituation and the GRIA1 (GluA1) AMPA receptor subunit. Mol Psychiatry 2014; 19: 1060-1070
50. Noorbala AA, Akhondzadeh S, Davari-Ashtiani R, Amini-Nooshabadi H. Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia. J Clin Pharm Ther 1999; 24: 369-374
51. Goff DC, Lamberti JS, Leon AC, Green MF, Miller AL, Patel J, et al A placebocontrolled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology 2008; 33: 465-472
52. Tsay D, Dudman JT, Siegelbaum SA. HCN1 channels constrain synaptically evoked Ca2+ spikes in distal dendrites of CA1 pyramidal neurons. Neuron 2007; 56: 1076-1089
53. Arnsten AF. Prefrontal cortical network connections: key site of vulnerability in stress and schizophrenia. Int J Dev Neurosci 2011; 29: 215-223
54. Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL. Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1125-1143
55. Kruse AC, Kobilka BK, Gautam D, Sexton PM, Christopoulos A, Wess J. Muscarinic acetylcholine receptors: novel opportunities for drug development. Nat Rev Drug Discov 2014; 13: 549-560
56. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2014; 506: 376-381
57. Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 2014; 385: 351-361
58. Grebb JA, Shelton RC, Taylor EH, Bigelow LB A negative, double-blind, placebocontrolled, clinical trial of verapamil in chronic schizophrenia. Biol Psychiatry 1986; 21: 691-694
59. Price WA. Antipsychotic effects of verapamil in schizophrenia. Hillside J Clin Psychiatry 1987; 9: 225-230
60. Yamada K, Kanba S, Ashikari I, Ohnishi K, Yagi G, Asai M. Nilvadipine is effective for chronic schizophrenia in a double-blind placebo-controlled study. J Clin Psychopharmacol 1996; 16: 437-439
61. Suddath RL, Straw GM, Freed WJ, Bigelow LB, Kirch DG, Wyatt RJ A clinical trial of nifedipine in schizophrenia and tardive dyskinesia. Pharmacol Biochem Behav 1991; 39: 743-745
62. Schwartz BL, Fay-McCarthy M, Kendrick K, Rosse RB, Deutsch SI. Effects of nifedipine, a calcium channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia. Clin Neuropharmacol 1997; 20: 364-370
63. Shekhar A, Potter WZ, Lightfoot J, Lienemann J, Dubé S, Mallinckrodt C, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry 2008; 165: 1033-1039
64. Kishi T, Iwata N. Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-Analysis. Eur Arch Psychiatry Clin Neurosci 2014 epub ahead of print
65. Roh S, Hoeppner SS, Schoenfeld D, Fullerton CA, Stoeckel LE, Evins AE. Acute effects of mecamylamine and varenicline on cognitive performance in nonsmokers with and without schizophrenia. Psychopharmacology (Berl) 2014; 231: 765-775
66. Sacco KA, Termine A, Dudas MM, Seyal AA, Allen TM, Vessicchio JC, Wexler BE, George TP. Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist. Schizophr Res 2006; 85: 213-221