Interaction networks of lithium and valproate molecular targets reveal a striking enrichment of apoptosis functional clusters and neurotrophin signaling

Pharmacogenomics Journal

Volumn 12, Issue 4, 2012, Pages 328-341

  Gupta, A ^a   Schulze, T G ^b   Nagarajan, V ^c   Akula, N ^a   Corona, W ^a   Jiang, X Y ^a   Hunter, N ^a   Mcmahon, F J ^a   Detera Wadleigh, S D ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

DAVID; expression; GLay; MiMI; pathways

Indexed keywords

CASPASE; CELL CYCLE PROTEIN; LITHIUM; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NEUROTROPHIN; PROTEIN KINASE B; VALPROIC ACID; WNT PROTEIN;

AKT1 GENE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BCL2 GENE; BDNF GENE; CATALYSIS; CELL CYCLE PROGRESSION; CELL DIVISION; CHROMAFFIN CELL; CONTROLLED STUDY; DNA METHYLATION; DOWN REGULATION; ENZYME ACTIVITY; GENE; GENE CLUSTER; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE INTERACTION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; IMPA1 GENE; LONG TERM POTENTIATION; MITOSIS; NONHUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION; UPREGULATION;

ANIMALS; APOPTOSIS; BIPOLAR DISORDER; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LITHIUM COMPOUNDS; MICE; NERVE GROWTH FACTORS; PHOSPHORIC MONOESTER HYDROLASES; PROTO-ONCOGENE PROTEINS C-AKT; RATS; SIGNAL TRANSDUCTION; TRANSCRIPTOME; VALPROIC ACID;

ACANTHAMOEBA POLYPHAGA MIMIVIRUS;

EID: 84864334532     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2011.9     Document Type: Article

References (101)

1. Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Australia 1949; 2: 349-352.
2. Belmaker RH. Bipolar disorder. N Engl J Med 2004; 351: 476-486.
3. Berridge MJ, Downes CP, Hanley MR. Neural and developmental actions of lithium: a unifying hypothesis. Cell 1989; 59: 411-419. (Pubitemid 19284456)
4. Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci 1996; 93: 8455-8459. (Pubitemid 26269579)
5. McColl G, Killilea DW, Hubbard AE, Vantipalli MC, Melov S, Lithgow GJ. Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans. J Biol Chem 2008; 283: 350-357.
6. Poustka AJ, Kühn A, Groth D, Weise V, Yaguchi S, Burke RD et al. A global view of gene expression in lithium and zinc treated sea urchin embryos: new components of gene regulatory networks. Genome Biol 2007; 8: R85.1-R85.18.
7. Bro C, Regenberg B, Lagniel G, Labarre J, Montero-Lomel M, Nielsen J. Transcriptional, proteomic, and metabolic responses to lithium in galactose-grown yeast cells. J Biol Chem 2003; 278: 32141-32149. (Pubitemid 37048404)
8. Manji HK, Moore GJ, Chen G. Bipolar disorder: leads from the molecular and cellular mechanisms of action of mood stabilizers. Br J Psychiatry Suppl 2001; 41: s107-s119. (Pubitemid 32530338)
9. Chuang D-M, Chen R-W, Chalecka-Franaszek E, Ren M, Hashimoto R, Senatorov V, Kanai H et al. Neuroprotective effects of lithium in cultured cells and animal models of diseases. Bipolar Disord 2002; 4: 129-136. (Pubitemid 34411275)
10. Göttlicher M, Minucci S, Zhu P, Krämer OH, Schimpf A, Giavara S et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 2001; 20: 6969-6978. (Pubitemid 34062289)
11. Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer and teratogen. J Biol Chem 2001; 276: 36734-36741.
12. Hao Y, Creson T, Zhang L, Li P, Du F, Yuan P, Gould TD et al. Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. J. Neurosci 2004; 24: 6590-6599. (Pubitemid 38971708)
13. Leng Y, Liang M-H, Ren M, Marinova Z, Leeds P, Chuang D-M. Synergistic neuroprotective effects of lithium and valproic acid or histone deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3 inhibition. J. Neurosci 2008; 28: 2576-2588. (Pubitemid 351348211)
14. Chalecka-Franaszek E, Chuang DM. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci USA 1999; 96: 8745-8750. (Pubitemid 29354862)
15. Sasaki T, Han F, Shioda N, Moriguchi S, Kasahara J, Ishiguro K et al. Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model. Brain Res 2006; 1108: 98-106. (Pubitemid 44278006)
16. Sinha D, Wang Z, Ruchalski KL, Levine JS, Krishnan S, Lieberthal W et al. Lithium activates the Wnt and phosphatidylinositol 3-kinase Akt signaling pathways to promote cell survival in the absence of soluble survival factors. Am J Physiol Renal Physiol 2005; 288: F703-F713. (Pubitemid 40381737)
17. Erdal E, Ozturk N, Cagatay T, Emel Eksioglu-Demiralp E, Ozturk M. Lithium-mediated downregulation of PKB/Akt and cyclin E with growth inhibition in hepatocellular carcinoma cells. Int J Cancer 2005; 115: 903-910. (Pubitemid 40791830)
18. Nemoto T, Kanai T, Yanagita T, Satoh S, Maruta T, Yoshikawa N et al. Regulation of Akt mRNA and protein levels by glycogen synthase kinase-3b in adrenal chromaffin cells: effects of LiCl and SB216763. Eur J Pharmacol 2008; 586: 82-89.
19. Zhang WV, Jüllig M, Connolly AR, Stott NS. Early gene response in lithium chloride induced apoptosis. Apoptosis 2005; 10: 75-90. (Pubitemid 40558116)
20. Nielsen J, Hoffert JD, Knepper MA, Agre P, Nielsen S, Fenton RA. Proteomic analysis of lithium-induced nephrogenic diabetes insipidus: mechanisms for aquaporin 2 down-regulation and cellular proliferation. Proc Natl Acad Sci USA 2008; 105: 3634-3639. (Pubitemid 351723604)
21. Zellmer S, Schmidt-Heck W, Gaunitz F, Baldysiak-Figie A, Guthke R, Gebhardt R. Dynamic network reconstruction from gene expression data describing the effect of LiCl stimulation on hepatocytes. J Integr Bioinform 2005; 2: 11-26.
22. McQuillin A, Rizig M, Gurling HM. A microarray gene expression study of the molecular pharmacology of lithium carbonate on mouse brain mRNA to understand the neurobiology of mood stabilization and treatment of bipolar affective disorder. Pharmacogenet Genomics 2007; 17: 605-617. (Pubitemid 47057710)
23. Chen R-W, Chuang D-M. Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. J Biol Chem 1999; 274: 6039-6042.
24. Chen G, Zeng WZ, Yuan PX, Huang LD, Jiang YM, Zhao ZH et al. The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 1999; 72: 879-882. (Pubitemid 29055256)
25. Huang X, Wu D-Y, Chen G, Manji H, Chen DF. Support of retinal ganglion cell survival and axon regeneration by lithium through a Bcl-2-dependent mechanism. Invest Ophthalmol Vis Sci 2003; 44: 347-354. (Pubitemid 36134295)
26. Bush AL, Hyson RL. Lithium increases Bcl-2 expression in chick cochlear nucleus and protects against deafferentation-induced cell death. Neuroscience 2006; 138: 1341-1349. (Pubitemid 43363550)
27. Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S. Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology 2001; 158: 100-106.
28. Omata N, Murata T, Takamatsu S, Maruoka N, Mitsuya H, Yonekura Y et al. Neuroprotective effect of chronic lithium treatment against hypoxia in specific brain regions with upregulation of cAMP response element binding protein and brain-derived neurotrophic factor but not nerve growth factor: comparison with acute lithium treatment. Bipolar Disord 2008; 10: 360-368. (Pubitemid 351517370)
29. Einat H, Yuan P, Gould TD, Li J, Du JH, Zhang L et al. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 2003; 23: 7311-7316. (Pubitemid 36999520)
30. Yasuda S, Liang MH, Marinova Z, Yahyavi A, Chuang DM. The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatry 2009; 14: 51-59.
31. Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA. Lithium treatment alters brain concentrations of nerve growth factor, brainderived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression. Int J Neuropsychopharmacol 2003; 6: 225-231. (Pubitemid 37248000)
32. O'Brien TW, Klein PS. Validating GSK3 as an in vivo target of lithium action. Biochem Soc Trans 2009; 37: 1133-1138.
33. Mendes CT, Mury FB, Mury, de Sa' Moreira E, Alberto FL, Forlenza OV et al. Lithium reduces GSK3b mRNA levels: implications for Alzheimer disease. Eur Arch Psychiatry Clin Neurosci 2009; 259: 16-22.
34. Parthasarathy LK, Seelan RS, Wilson MA, Parthasarathy RN. Regional changes in rat brain inositol monophosphatase I (IMPase 1) activity with chronic lithium treatment. Prog Neuro-Psychophamacol Biol Psychiatry 2002; 27: 55-60.
35. Shamir A, Shaltiel G, Greenberg ML, Belmaker RH, Agam G. The effect of lithium on expression of genes for inositol biosynthetic enzymes in mouse hippocampus; a comparison with the yeast model. Brain Res Mol Brain Res 2003; 115: 104-110. (Pubitemid 36859860)
36. Fatemi SH, Reutiman TJ, Folsom TD. The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder. Biochem Soc Trans 2009; 37: 1090-1095.
37. Rodriguez ML, Yubero P, Iglesias R, Giralt M, Villarroya F. Lithium inhibits brown adipocyte differentiation. FEBS Lett 2005; 579: 1670-1674. (Pubitemid 40341541)
38. Seelan RS, Khalyfa A, Lakshmanan J, Casanova MF, Parthasarathy RN. Deciphering the lithium transcriptome: microarray profiling of lithiummodulated gene expression in human neuronal cells. Neuroscience 2008; 151: 1184-1197.
39. Brandish PE, Su M, Holder DJ, Hodor P, Szumiloski J, Kleinhanz RR et al. Regulation of gene expression by lithium and depletion of inositol in slices of adult rat cortex. Neuron 2005; 45: 861-872. (Pubitemid 40395265)
40. Cordeiro ML, Umbach JA, Gundersen CB. Lithium ions up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factordifferentiated PC12 cells. J Neurochem 2000; 75: 2622-2625.
41. Corena-McLeod M dP, Oliveros A, Charlesworth C, Madden B, Liang YQ, Boules M et al. Paliperidone as a mood stabilizer: a pre-frontal cortex synaptoneurosomal proteomics comparison with lithium and valproic acid after chronic treatment reveals SIMilarities in protein expression. Brain Res 2008; 1233: 8-19.
42. Bosetti F, Seemann R, Bell JM, Zahorchak R, Friedman E, Rapoport SI et al. Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42 days of oral lithium administration. Brain Res Bull 2002; 57: 205-209. (Pubitemid 34155394)
43. Hallcher LM, Sherman WR. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem 1980; 255: 10896-10901. (Pubitemid 11171746)
44. Adams JM, Cory S. The bcl-2 protein family: arbiters of cell survival. Science 1998; 281: 1322-1326. (Pubitemid 28406819)
45. Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang D-M. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002; 43: 1173-1179. (Pubitemid 36009371)
46. Chetcuti A, Adams LJ, Mitchell PB, Schofield PR. Microarray gene expression profiling of mouse brain mRNA in a model of lithium treatment. Psychiatr Genet 2008; 18: 64-72. (Pubitemid 351654723)
47. Wood JR, Nelson-Degrave VL, Jansen E, McAllister JM, Mosselman S, Strauss III JF. Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects. Physiol Genomics 2005; 20: 233-243. (Pubitemid 40388523)
48. Chen J, Ghazawi FM, Bakkar W, Li Q. Valproic acid and butyrate induce apoptosis in human cancer cells through inhibition of gene expression of Akt/protein kinase B. Mol Cancer 2006; 5: 71.
49. Creson TK, Yuan P, Manji HK, Chen G. Evidence for the involvement of ERK, PI3 K, and RSK in induction of Bcl-2 by valproate. J Mol Neurosci 2009; 37: 123-134.
50. Fukuchi M, Nii T, Ishimaru N, Minamino A, Hara D, Takasaki I, Tabuchi A, Tsuda M. Valproic acid induces up-or down-regulation of gene expression responsible for the neuronal excitation and inhibition in rat cortical neurons through its epigenetic actions. Neurosci Res 2009; 65: 35-43.
51. Gurpur PV, Liu J, Burkin DJ, Kaufman SJ. Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. Am J Pathol 2009; 174: 999-1008.
52. Shen WT, Wong TS, Chung W-Y, Wong MG, Kebebew E, Duh Q-Y, Clark OH. Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells. Surgery 2005; 138: 979-985. (Pubitemid 41797335)
53. Wu X, Chen PS, Dallas S, Wilson B, Block ML, Wang C-C et al. Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int J Neuropsychopharmacol 2008; 11: 1123-1134.
54. de Sarno P, Li X, Jope RS. Regulation of Akt and glycogen synthase-3b phosphorylation by sodium valproate and lithium. Neuropharmacology 2002; 43: 1158-1164. (Pubitemid 36009369)
55. Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 2005; 118: 89-99. (Pubitemid 40277107)
56. Jurata LW, Bukhman YV, Charles V, Capriglione F, Bullard J, Lenire AL et al. Comparison of microarray-based mRNA profiling technologies for identification of psychiatric disease and drug signatures. J Neurosci Methods 2004; 138: 173-188. (Pubitemid 39485990)
57. Milutinovic S, D'Alessio AC, Detich N, Szyf M. Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. Carcinogenesis 2007; 28: 560-571. (Pubitemid 46523352)
58. Jergil M, Kultima K, Gustafson A-L, Dencker L, Stigson M. Valproic acid-induced deregulation in vitro of genes associated with neural tube defects. Toxicol Sci 2009; 108: 132-148.
59. Stamatopoulos B, Meuleman N, De Bruyn, Mineur P, Martiat P, Bron D, Lagneaux L. Antileukemic activity of valproic acid in chronic lymphocytic leukemia B cells defined by microarray analysis. Leukemia 2009; 23: 2281-2289.
60. Sugawara H, Iwamoto K, Bundo M, Ishiwata M, Ueda J, Kakiuchi C et al. Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm 2010; 117: 155-164.
61. Kultima K, Nyström A-M, Scholz B, Gustafson A-L, Dencker L, Stigson M. Valproic acid teratogenicity: a toxicogenomics approach. Environ Health Persp 2004; 112: 1225-1234.
62. Kultima K, Jergil M, Salter H, Gustafson A-L, Dencker L, Stigson M. Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenecity. Reprod Toxicol 2010; 30: 457-468.
63. Ogden CA, Rich ME, Schork NJ, Paulus MP, Geyer MA, Lohr JB et al. Candidate genes, pathways and mechanisms for bipolar disorder (manic-depressive) and related disorders: an expanded convergent functional genomics approach. Mol Psychiatry 2004; 9: 1007-1029. (Pubitemid 39524290)
64. Bosetti F, Bell KM, Manickam P. Microarray analysis of rat brain gene expression after chronic administration of sodium valproate. Brain Res Bull 2005; 65: 331-338. (Pubitemid 41057803)
65. Chetcuti A, Adams LJ, Mitchell PB, Schofield PR. Altered gene expression in mice treated with the mood stabilizer sodium valproate. Int J Neuropsychopharmacol 2005; 9: 267-276.
66. Wang J-F, Bown C, Young LT. Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78. Mol Pharmacol 1999; 55: 521-527. (Pubitemid 29128109)
67. Baumeister P, Dong D, Fu Y, Lee AS. Transcriptional induction of GRP78/BiP by histone deacetylase inhibitors and resistance to histone deacetylase inhibitor-induced apoptosis. Mol Cancer Ther 2009; 8: 1086-1094.
68. Venkataramani V, Rossner C, Iffland L, Schweyer S, Tamboli IY, Walter J et al. Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the Alzheimer amyloid precursor protein. J Biol Chem 2010; 285: 10678-10689.
69. Watson DG, Watterson JM, Lenox RH. Sodium valproate down-regulates the myristoylated alanine-rich C kinase substrate (MARCKS) in immortalized hippocampal cells: a property of protein kinase C-mediated mood stabilizers. J Pharmacol Expt Ther 1998; 285: 307-316. (Pubitemid 28207601)
70. Jayapandian M, Chapman A, Tarcea VG, Yu C, Elkiss A, Ianni A et al. Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together. Nucl Acids Res 2007; 35: D566-D571. (Pubitemid 46056271)
71. Gao J, Ade AS, Tarcea VG, Weymouth T E, Mirel BR, Jagadish HV, States DJ. Integrating and Annotating the Interactome using the MiMI plugin for Cytoscape. Bioinformatics 2009; 25: 137-138.
72. Ferrell Jr JE. Q&A: Systems biology. J Biol 2009; 8: 2.
73. Su G, Kuchinsky A, Morris JH, States DJ, Meng F. GLay: community structure analysis of biological networks. Bioinformatics 2010; 26: 3135-3137.
74. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. Nat Protoc 2009; 4: 44-57.
75. Nakatani N, Hattori E, Ohnishi T, Dean B, Iwayama Y, Matsumoto I et al. Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation. Hum Mol Genet 2006; 15: 1949-1962. (Pubitemid 43983269)
76. Gonzalez E, McGraw TE. The Akt kinases. Cell Cycle 2009; 8: 2502-2508.
77. Lee HJ, Kim MK, Hee J, Kim HJ, Kim SU. Human neural stem cells genetically modified to overexpress Akt1 provide neuroprotection and functional improvement in mouse stroke model. PLoS ONE 2009; 4: e5586.
78. Beaulieu J-M, Gainetdinov RR, Caron MG. Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol 2009; 49: 327-347.
79. Lai W-S, Xu B, Westphal KGC, Paterlini M, Olivier B, Pavlidis P et al. Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. Proc Natl Acad Sci USA 2006; 103: 16906-16911. (Pubitemid 44737351)
80. Satoh Y, Endo S, Ikeda T, Yamada K, Ito M, Kuroki M et al. Extracellular signal-regulated kinase 2 (ERK2) knockdown mice show deficits in long-term; ERK2 has a specific function in learning and memory. J Neurosci 2007; 27: 10765-10776. (Pubitemid 47535863)
81. Mazzucchelli C, Vantaggiato C, Ciamei A, Fasano S, Pakhotin P, Krezel W et al. Knockout of ERK1/MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory. Neuron 2002; 34: 807-820. (Pubitemid 34628742)
82. Detera-Wadleigh SD. Lithium-related genetics of bipolar disorder. Ann Med 2001; 33: 272-285. (Pubitemid 32500410)
83. Alda M, Grof P, Rouleau GA, Turecki G, Young LT. Investigating responders to lithium prophylaxis as a strategy for mapping susceptibility genes for bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 1038-1045. (Pubitemid 41080131)
84. Cruceanu C, Alda M, Turecki G. Lithium: a key to the genetics of bipolar disorder. Genome Med 2009; 1: 79.
85. Detera-Wadleigh SD, Yoshikawa T. Decoding the genetics and underlying mechanisms of mood disorders. In: Wildernauer D (ed). Molecular Biology of Psychiatric Disorders, Gross HJ (ed). Nucleic Acids and Molecular Biology 23 Springer-Verlag: Berlin Heidleberg, 2009 pp 1-50.
86. Perlis RH, Smoller JW, Ferreira MA, McQuillin A, Bass N, Lawrence J et al. A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder. Am J Psychiatry 2009; 166: 718-725.
87. Schulze TG, Alda M, Adli M, Akula N, Ardau R, Chillotti C et al. The international consortium on lithium genetics (ConLigen)-an initiative by the NIMH and IGSLI to study the genetic basis of response to lithium treatment. Neuropsychobiology 2010; 62: 72-78.
88. Ferreira MAR, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40: 1056-1058.
89. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe'er I, Dudbridge F et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009; 460: 753-757.
90. McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD et al. Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1. Nat Genet 2010; 42: 128-131.
91. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 2004; 36: 131-137. (Pubitemid 38174370)
92. Toyota T, Yamada K, Detera-Wadleigh SD, Yoshikawa T. Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees: a familybased association study. Neuroscience Lett 2003; 339: 5-8. (Pubitemid 36263208)
93. Pietiläinen OP, Paunio T, Loukola A, Tuulio-Henriksson A, Kieseppä T, Thompson P et al. Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins. Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 683-692.
94. Kim JY, Duan X, Liu CY, Jang MH, Guo JU, Pow-anpongku N et al. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 2009; 63: 761-773.
95. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell 2009; 136: 1017-1031.
96. Brandon NJ, Millar JK, Korth C, Sive H, Singh KK, Sawa A. Understanding the role of DISC1 in psychiatric disease and during normal development. J Neurosci 2009; 29: 12768-12775.
97. St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G et al. Association within a family of a balanced autosomal translocation with major mental illness. Lancet 1990; 336: 13-16. (Pubitemid 20207869)
98. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 2000; 9: 1415-1423. (Pubitemid 30312490)
99. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disorders-cosegregation with a translocation at chromosome 1q42 that directly disrupts brainexpressed genes: clinical and P300 findings in a family. Am J Hum Genet 2001; 69: 428-433. (Pubitemid 32695214)
100. Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877-892. (Pubitemid 135750519)
101. Goes FS, Willour VL, Zandi PP, Belmonte PL, MacKinnon DF, Mondimore FM et al. Family-based association study of Neuregulin 1 with psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 693-702.