Cell and Tissue Research

, Volume 357, Issue 2, pp 477–492 | Cite as

Calcium signalling and psychiatric disease: bipolar disorder and schizophrenia

  • Michael J. BerridgeEmail author


Neurons have highly developed Ca2+ signalling systems responsible for regulating many neural functions such as the generation of brain rhythms, information processing and the changes in synaptic plasticity that underpins learning and memory. The signalling mechanisms that regulate neuronal excitability are particularly important for processes such as sensory perception, cognition and consciousness. The Ca2+ signalling pathway is a key component of the mechanisms responsible for regulating neuronal excitability, information processing and cognition. Alterations in gene transcription are particularly important as they result in subtle alterations in the neuronal signalling mechanisms that have been implicated in many neural diseases. In particular, dysregulation of the Ca2+ signalling pathway has been implicated in the development of some of the major psychiatric diseases such as bipolar disorder (BPD) and schizophrenia.


Calcium Inositol trisphosphate Schizophrenia Bipolar disease Reactive oxygen species 


  1. Agam G, Shamir A, Shaltiel G, Greenberg ML (2002) Myo-inositol-1-phosphate (MIP) synthase: a possible new target for antibipolar drugs. Bipolar Disord 4 (Suppl 1):15–20PubMedGoogle Scholar
  2. Agam G, Bersudsky Y, Berry GT, Moechars D, Lavi-Avnon Y, Belmaker RH (2009) Knockout mice in understanding the mechanism of action of lithium. Biochem Soc Trans 37:1121–1125PubMedGoogle Scholar
  3. Alexandre C, Andermann ML, Scammell TE (2013) Control of arousal by the orexin neurons. Curr Opin Neurobiol 23:752–759PubMedGoogle Scholar
  4. Allison JH, Stewart MA (1971) Reduced brain inositol in lithium-treated rats. Nat New Biol 233:267–268PubMedGoogle Scholar
  5. 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 (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13:197–207PubMedCentralPubMedGoogle Scholar
  6. Behrens MM, Sejnowski TJ (2009) Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex? Neuropharmacology 57:193–200PubMedCentralPubMedGoogle Scholar
  7. Belmaker RH, Bersudsky Y, Agam G, Levine J, Kofman O (1996) How does lithium work on manic depression? Clinical and psychological correlates of the inositol theory. Annu Rev Med 47:47–56PubMedGoogle Scholar
  8. Bendikov I, Nadri C, Amar S, Panizzutti R, De Miranda J, Wolosker H, Agam G (2007) A CSF and post-mortem brain study of D-serine metabolic parameters in schizophrenia. Schizophr Res 90:41–51PubMedGoogle Scholar
  9. Berk M, Ng F, Dean O, Dodd S, Bush AI (2008) Glutathione: a novel treatment target in psychiatry. Trends Pharmacol Sci 29:346–351PubMedGoogle Scholar
  10. Berk M, Malhi GS, Gray LJ, Dean OM (2013) The promise of N-acetylcysteine in neuropsychiatry. Trend Pharm Sci 34:167–177Google Scholar
  11. Berridge MJ (2012a) Calcium signalling remodelling and disease. Biochem Soc Trans 40:297–309PubMedGoogle Scholar
  12. Berridge MJ (2012b) Dysregulation of neural calcium signalling in Alzheimer disease, bipolar disorder and schizophrenia. Prion 6:1–12Google Scholar
  13. Berridge MJ (2014) Calcium regulation of neural rhythms, memory and Alzheimer’s disease. J Physiol (Lond) 592:281–293Google Scholar
  14. Berridge MJ, Downes CP, Hanley MR (1982) Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 206:587–595PubMedCentralPubMedGoogle Scholar
  15. Berridge MJ, Downes CP, Hanley MR (1989) Neural and developmental actions of lithium: a unifying hypothesis. Cell 59:411–419PubMedGoogle Scholar
  16. Bigos KL, Mattay VS, Callicott JH, Straub RE, Vakkalanka R, Kolachana B, Hyde TM, Lipska BK, Kleinman JE, Weinberger DR (2010) Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67:939–945PubMedCentralPubMedGoogle Scholar
  17. Buonanno A (2010) The neuregulin signaling pathway and schizophrenia: from genes to synapses and neural circuits. Brain Res Bull 83:122–131PubMedCentralPubMedGoogle Scholar
  18. Chang P, Orabi B, Deranieh RM, Dham M, Hoeller O, Shimshoni JA, Yagen B, Bialer M, Greenberg ML, Walker MC, Williams RSB (2012) The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium. Dis Model Mech 5:115–124PubMedCentralPubMedGoogle Scholar
  19. Chang P, Walker MC, Williams RS (2014) Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid. Neurobiol Dis 62:296–306PubMedCentralPubMedGoogle Scholar
  20. Chen G, Zeng WZ, Yuan PX, Huang LD, Jiang YM, Zhao ZH (1999) The mood-stabilizing agents lithium and valproate robustly increase levels of the neuroprotective protein Bcl-2 in the CNS. J Neurochem 72:879–882PubMedGoogle Scholar
  21. Chiu C-T, Wang Z, Hunsberger JG, Chuang D-M (2013) Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder. Pharmacol Rev 65:105–142PubMedCentralPubMedGoogle Scholar
  22. Chumakov I, Blumenfeld M, Guerassimenko CL, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P et al (2002) Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci U S A 99:13675–13680PubMedCentralPubMedGoogle Scholar
  23. Corvin A, McGhee KA, Murphy K, Donohoe G, Nangle JM, Schwaiger S, Kenny N, Clarke S, Meagher D, Quinn J, Scully P, Baldwin P, Browne D, Walsh C, Waddington JL, Morris DW, Gill M (2007) Evidence for association and epistasis at the DAOA/G30 and D-amino acid oxidase loci in an Irish schizophrenia sample. Am J Med Genet B 144B:949–953Google Scholar
  24. Coyle JT (2006) Glutamate and schizophrenia: beyond the dopamine hypothesis. Cell Mol Neurobiol 26:363–382Google Scholar
  25. Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381:1371–1379PubMedCentralGoogle Scholar
  26. Curley AA, Lewis DA (2012) Cortical basket cell dysfunction in schizophrenia. J Physiol (Lond) 590:715–724Google Scholar
  27. Datta S (2010) Cellular and chemical neuroscience of mammalian sleep. Sleep Med 11:431–440PubMedCentralPubMedGoogle Scholar
  28. Dean OM, van den Buuse M, Bush AI, Copolov DL, Ng F, Dodd S, Berk M (2009) A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice. Curr Med Chem 16:2965–2976PubMedGoogle Scholar
  29. Diez-Guerra FJ (2010) Neurogranin, a link between calcium/calmodulin and protein kinase C signalling in synaptic plasticity. IUBMB Life 62:597–606PubMedGoogle Scholar
  30. Do KQ, Cabungcal JH, Frank A, Steullet P, Cuenod M (2009) Redox dysregulation, neurodevelopment, and schizophrenia. Curr Opin Neurobiol 19:220–230PubMedGoogle Scholar
  31. Edlow BL, Takahashi E, Wu O, Benner T, Dai G, Bu L, Grant PE, Greer DM, Greenberg SM, Kinney HC, Folkerth RD (2012) Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders. J Neuropathol Exp Neurol 71:531–546PubMedCentralPubMedGoogle Scholar
  32. Eickholt BJ, Towers GJ, Ryves WJ, Eikel D, Adley K, Ylinen LM, Chadborn NH, Harwood AJ, Nau H, Williams RS (2005) Effects of valproic acid derivatives on inositol trisphosphate depletion, teratogenicity, glycogen synthase kinase-3 beta inhibition, and viral replication: a screening approach for new bipolar disorder drugs derived from the valproic acid core structure. Mol Pharmacol 67:1426–1433PubMedCentralPubMedGoogle Scholar
  33. Erk S, Meyer-Lindenberg A, Schnell K, Opitz von Boberfeld C, Esslinger C, Kirsch P, Grimm O, Arnold C, Haddad L, Witt SH, Cichon S, Nöthen MM, Rietschel M, Walter H (2010) Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 67:803–811PubMedGoogle Scholar
  34. Ferreira MAR, O’Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, Fan J, Kirov G, Perlis RH, Green EK, Smoller JW, Grozeva D, Stone J, Nikolov I, Chambert K et al (2008) Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 40:1056–1058PubMedCentralPubMedGoogle Scholar
  35. Flavell SW, Greenberg ME (2008) Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu Rev Neurosci 31:563–590PubMedCentralPubMedGoogle Scholar
  36. Gauthier J, Champagne N, Lafrenière RG, Xiong L, Spiegelman D, Edna Brustein E et al (2010) De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proc Natl Acad Sci U S A 107:7863–7868PubMedCentralPubMedGoogle Scholar
  37. Gee NS, Ragan CI, Watling KJ, Aspley S, Jackson RG, Reid GG, Cl G, Shute JK (1988) The purification and properties of myoinositol monophosphatase from bovine brain. Biochem J 249:883–889PubMedCentralPubMedGoogle Scholar
  38. Giegling I, Genius J, Benninghoff J, Rujescu D (2010) Genetic findings in schizophrenia patients related to alterations in the intracellular Ca-homeostasis. Prog Neuropsychopharm Biol Psychiatr 34:1375–1380Google Scholar
  39. Gonzalez-Burgos G, Lewis DA (2008) GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull 34:944–961PubMedCentralPubMedGoogle Scholar
  40. Gonzalez-Burgos G, Lewis DA (2012) NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia. Schizophr Bull 38:950–957PubMedCentralPubMedGoogle Scholar
  41. Greenwood TA, Schork NJ, Eskin E, Kelsoe JR (2006) Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples. Mol Psychiatry 11:125–133PubMedGoogle Scholar
  42. Guella I, Sequeira A, Rollins B, Morgan L, Torri F, van Erp TG, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Bunney WE, Potkin SG, Macciardi F, Vawter MP (2013) Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. J Psychiatr Res 47:1215–1221PubMedGoogle Scholar
  43. Guilmatre A, Huguet G, Delorme R, Bourgeron T (2014) The emerging role of SHANK genes in neuropsychiatric disorders. Dev Neurobiol 74:113–122PubMedGoogle Scholar
  44. Hardingham GE, Bading H (1999) Calcium as a versatile second messenger in the control of gene expression. Microsc Res Tech 46:348–355PubMedGoogle Scholar
  45. Hardingham GE, Bading H (2010) Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nat Rev Neurosci 11:682–696PubMedCentralPubMedGoogle Scholar
  46. Harvey AG (2008) Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation. Am J Psychiatry 165:820–829PubMedGoogle Scholar
  47. Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindström LH, Iyo M (2005) Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharm Biol Psychiatr 29:767–769Google Scholar
  48. Hsin H, Kim MJ, Wang CF, Sheng M (2010) Proline-rich tyrosine kinase 2 regulates hippocampal long-term depression. J Neurosci 30:11983–11993PubMedGoogle Scholar
  49. Hur E-M, Zhou F-Q (2010) GSK3 signalling in neural development. Nat Rev Neurosci 11:539–551PubMedCentralPubMedGoogle Scholar
  50. Jagannath A, Peirson SN, Foster RG (2013) Sleep and circadian rhythm disruption in neuropsychiatric illness. Curr Opin Neurobiol 23:888–894PubMedGoogle Scholar
  51. Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301–1308PubMedGoogle Scholar
  52. Kantrowitz JT, Javitt DC (2010) N-methyl-D-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Res Bull 83:108–121PubMedCentralPubMedGoogle Scholar
  53. Kim HJ, Thayer SA (2009) Lithium increases synapse formation between hippocampal neurons by depleting phosphoinositides. Mol Pharmacol 75:1021–1030PubMedCentralPubMedGoogle Scholar
  54. Kofman O, Belmaker RH (1990) Intracerebroventricularmyo-inositol antagonizes lithium-induced suppression of rearing behaviour in rats. Brain Res 534:345–347PubMedGoogle Scholar
  55. Koh PO, Undie AS, Kabbani N, Levenson R, Goldman-Rakic PS, Lidow MS (2003) Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients. Proc Natl Acad Sci U S A 100:313–317PubMedCentralPubMedGoogle Scholar
  56. Krug A, Krach S, Jansen A, Nieratschker V, Witt SH, Shah NJ, Nöthen MM, Rietschel M, Kircher T (2013) The effect of neurogranin on neural correlates of episodic memory encoding and retrieval. Schizophr Bull 39:141–150PubMedCentralPubMedGoogle Scholar
  57. Labrie V, Roder JC (2010) The involvement of the NMDA receptor D-serine/glycine site in the pathophysiology and treatment of schizophrenia. Neurosci Biobehav Rev 34:351–372PubMedGoogle Scholar
  58. Lacinova L, Moosmang S, Langwieser N, Hofmann F, Kleppisch T (2008) Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal cells. Life Sci 82:41–49PubMedGoogle Scholar
  59. Lee K-H, Williams LM, Breakspear M, Gordon E (2003) Synchronous gamma activity: a review and contribution to an integrative neuroscience model of schizophrenia. Brain Res Rev 41:57–78PubMedGoogle Scholar
  60. Lewis DA, Sweet RA (2009) Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies. J Clin Invest 110:706–709Google Scholar
  61. Li X, Jope RS (2010) Is glycogen synthase kinase-3 a central modulator of mood regulation? Neuropsychopharmacology 35:2143–2154PubMedCentralPubMedGoogle Scholar
  62. Lidow MS (2003) Calcium signaling dysfunction in schizophrenia: a unifying approach. Brain Res Brain Res Rev 43:70–84PubMedGoogle Scholar
  63. Lisman J (2012) Excitation, inhibition, local oscillations, or large-scale loops: what causes the symptoms of schizophrenia? Curr Opin Neurobiol 22:537–544PubMedCentralPubMedGoogle Scholar
  64. Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234–242PubMedCentralPubMedGoogle Scholar
  65. Liu L, Forouda T, Xueia X, Berrettinib W, Byerleyc W, Coryelld W et al (2008) Evidence of association between brain-derived neurotrophic factor (BDNF) gene and bipolar disorder. Psychiatr Genet 18:267–274PubMedCentralPubMedGoogle Scholar
  66. Lovestone S, Killick R, Di Forti M, Murray R (2007) Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci 30:142–149PubMedGoogle Scholar
  67. Machado-Vieira R, Manji HK, Zarate AC (2009) The role of lithium in the treatement of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 11:92–109PubMedCentralPubMedGoogle Scholar
  68. Machado-Vieira R, Pivovarova NB, Stanika RI, Yun Wang PY, Zhou R, Zarate CA et al (2010) The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor–mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry 69:344–352PubMedCentralPubMedGoogle Scholar
  69. Mahli GS, Tenious M, Das P, Coulston CM, Berk M (2013) Potential mechanisms of action of lithium in bipolar disorder. CNS Drugs 27:135–153Google Scholar
  70. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK et al (2009) Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signalling. Cell 136:1017–1031PubMedCentralPubMedGoogle Scholar
  71. Martinowich K, Schloesser RJ, Manji HK (2009) Bipolar disorder: from genes to behaviour pathways. J Clin Invest 119:726–736PubMedCentralPubMedGoogle Scholar
  72. Matosin N, Newell KA (2013) Metabotropic glutamate receptor 5 in the pathology and treatment of schizophrenia. Neurosci Biobehav Rev 37:256–268PubMedGoogle Scholar
  73. McClung CA (2013) How might circadian rhythms control mood? Let me count the ways. Biol Psychiatry 74:242–249PubMedGoogle Scholar
  74. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M (2011) Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12:524–538PubMedGoogle Scholar
  75. Missiaen L, Taylor CW, Berridge MJ (1991) Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores. Nature 352:241–244PubMedGoogle Scholar
  76. Moosmang S, Haider N, Klugbauer N, Adelsberger H, Langwieser N, Müller J, Stiess M, Marais E, Schulla V, Lacinova L, Goebbels S, Nave KA, Storm DR, Hofmann F, Kleppisch T (2005) Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci 25:9883–9892PubMedGoogle Scholar
  77. Morita Y, Ujike H, Tanaka Y, Otani K, Kishimoto M, Morio A, Kotaka T, Okahisa Y, Matsushita M, Morikawa A, Hamase K, Zaitsu K, Kuroda S (2007) A genetic variant of the serine racemase gene is associated with schizophrenia. Biol Psychiatry 61:1200–1203PubMedGoogle Scholar
  78. Najjr S, Pearlman DM, Alper K, Najjar A, Devinsky O (2013) Neuroinflammation and psychiatric illness. J Neuroinflammation 10:43–67Google Scholar
  79. Nakazawa K, Zsirosa V, Jiang Z, Nakao K, Kolata S, Zhang S, Belforte JE (2012) GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 62:1574–1583PubMedCentralPubMedGoogle Scholar
  80. Ohi K, Hashimoto R, Yasuda Y, Nemoto K, Ohnishi T, Fukumoto M, Yamamori H, Umeda-Yano S, Okada T, Iwase M, Kazui H, Takeda M (2012) Impact of the genome wide supported NRGN gene on anterior cingulate morphology in schizophrenia. PLoS ONE 7:e29780PubMedCentralPubMedGoogle Scholar
  81. Pace-Schott EF, Hobson JA (2002) The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3:591–605PubMedGoogle Scholar
  82. Pitcher GM, Kalia LV, Ng D, Goodfellow NM, Yee KT, Lambe EK, Salter MW (2011) Schizophrenia susceptibility pathway neuregulin 1–ErbB4 suppresses Src upregulation of NMDA receptors. Nat Med 17:470–478PubMedCentralPubMedGoogle Scholar
  83. Qiu Z, Ghosh A (2008) A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression. Neuron 60:775–787PubMedCentralPubMedGoogle Scholar
  84. Quiroz JA, Machado-Vieira R, Zarate CA, Manji HK (2010) Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology 62:50–60PubMedCentralPubMedGoogle Scholar
  85. Ritter PS, Kretschmer K, Pfennig A, Soltmann B (2013) Disturbed sleep in bipolar disorder is related to an elevation of IL-6 in peripheral monocytes. Med Hypotheses 81:1031–1033PubMedGoogle Scholar
  86. Rong YP, Distelhorst CW (2008) Bcl-2 protein family: versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol 70:73–91PubMedGoogle Scholar
  87. Ross CA, Margolis RL, Reading SAJ, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52:139–153PubMedGoogle Scholar
  88. Rowe MK, Wiest C, De-Maw Chuang D-W (2007) GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder. Neurosci Biobehav Rev 31:920–931PubMedCentralPubMedGoogle Scholar
  89. Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8:171–181PubMedGoogle Scholar
  90. Salvadore G, Quiroz JA, Machado-Vieira R, Henter ID, Manji HK, Zarate CA Jr (2010) The neurobiology of the switch process in bipolar disorder: a review. J Clin Psychiatry 71:1488–1501PubMedCentralPubMedGoogle Scholar
  91. Saper CB, Scammell TE, Lu J (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257–1263PubMedGoogle Scholar
  92. Sayas CL, Atiaens A, Ponsioen B, Moolenaar WH (2006) GSK-3 is activated by the tyrosine kinase Pyk2 during LPA1-mediated neurite retraction. Mol Biol Cell 17:1834–1844PubMedCentralPubMedGoogle Scholar
  93. Scarr E, Dean B (2008) Muscarinic receptors: do they have a role in the pathology and treatment of schizophrenia. J Neurochem 107:1188–1195PubMedGoogle Scholar
  94. Schlecker C, Boehmerle W, Jeromin A, DeGray B, Varshney A, Sharma Y et al (2006) Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. J Clin Invest 116:1668–1674PubMedCentralPubMedGoogle Scholar
  95. Schwartz JRL, Roth T (2008) Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharm 6:367–378Google Scholar
  96. Shaltiel G, Shamir A, Shapiro J, Ding D, Dalton E, Bialer M, Harwood AJ, Belmaker RH, Greenberg ML, Agam G (2004) Valproate decreases inositol biosynthesis. Biol Psychiatry 56:868–874PubMedGoogle Scholar
  97. Sharma G, Vijayaraghavan S (2003) Modulation of presynaptic store calcium induces release of glutamate and postsynaptic firing. Neuron 38:929–939PubMedGoogle Scholar
  98. Shinkai T, De Luca V, Hwang R, Muller DJ, Lanktree M, Zai G, Shaikh S, Wong G, Sicard T, Potapova N, Trakalo J, King N, Matsumoto C, Hori H, Wong AHC, Ohmori O, Macciardi F, Nakamura J, Kennedy JL (2007) Association analyses of the DAOA/G30 and D amino-acid oxidase genes in schizophrenia: further evidence for a role in schizophrenia. Neuromol Med 9:169–177Google Scholar
  99. Singh N, Halliday AC, Thomas JM, Kuznetsova OV, Baldwin R, Woon EC, Aley PK, Antoniadou I, Sharp T, Vasudevan SR, Churchill GC (2013) A safe lithium mimetic for bipolar disorder. Nat Commun 4:1332PubMedCentralPubMedGoogle Scholar
  100. Sklar P, Smoller JW, Fan J, Ferreira MAR, Perlis RH, Chambert K, Nimgaonkar VL, McQueen MB, Faraone SV, Kirby A, de Bakker PIW, Ogdie MN, Thase ME, Sachs GS, Todd-Brown K, Gabriel SB, Sougnez C, Gates C, Blumenstiel B, Defelice M, Ardlie KG, Franklin J, Muir WJ, McGhee KA, MacIntyre DJ, McLean A, VanBeck M, McQuillin A, Bass NJ, Robinson M, Lawrence J, Anjorin A, Curtis D, Scolnick EM, Daly MJ, Blackwood DH, Gurling HM, Purcell SM (2008) Whole-genome association study of bipolar disorder. Mol Psychiatry 13:558–569PubMedCentralPubMedGoogle Scholar
  101. Snyder MA, Gao W-J (2013) NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front Cell Neurosci 7:1–12Google Scholar
  102. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT (2004) Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119:19–31PubMedGoogle Scholar
  103. Suh B-C, Hille B (2002) Recovery of muscarinic modulation of M channels requires phosphatidylinositol 4,5-bisphosphate synthesis. Neuron 35:507–520PubMedGoogle Scholar
  104. Suh B-C, Leal K, Hille B (2013) Modulation of high-voltage activated Ca2+ channels by membrane phosphatidylinositol 4,5-bisphosphate. Neuron 67:224–238Google Scholar
  105. Thrower EC, Duclohier H, Lea EJA, Molle G, Dawson AP (1996) The inositol 1,4,5-trisphosphate-gated Ca22+ channel: effect of the protein thiol reagent thimerosal on channel activity. Biochem J 318:61–66PubMedCentralPubMedGoogle Scholar
  106. Touriño C, Eban-Rothschild A, de Lecea L (2013) Optogenetics in psychiatric diseases. Curr Opin Neurobiol 23:430–435PubMedCentralPubMedGoogle Scholar
  107. Uhlaas PJ (2013) Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia. Curr Opin Neurobiol 23:283–290Google Scholar
  108. Uhlhaas PJ, Singer W (2010) Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11:100–113PubMedGoogle Scholar
  109. Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC (2000) Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. Arch Gen Psychiatry 57:1139–1147PubMedGoogle Scholar
  110. Vacic V, McCarthy S, Malhotra D, Murray F, Chou H-H, Peoples A et al (2011) Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 471:499–503PubMedCentralPubMedGoogle Scholar
  111. Warsh JJ, Andreopoulos S, Li PP (2004) Role of intracellular calcium signaling in the pathophysiology and pharmacotherapy of bipolar disorder: current status. Clin Neurosci Res 4:201–213Google Scholar
  112. Wright C, Turner JA, Calhoun VD, Perrone-Bizzozero N (2013) Potential impact of miR-137 and its targets in schizophrenia. Front Genet 4:58PubMedCentralPubMedGoogle Scholar
  113. Wu GY, Deisseroth K, Tsien RW (2001) Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway. Proc Natl Acad Sci U S A 98:2808–2813PubMedCentralPubMedGoogle Scholar
  114. Zarate CA, Manji HK (2009) Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 23:569–582PubMedCentralPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.The Babraham InstituteCambridgeUK

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