The impact of a CACNA1C gene polymorphism on learning and hippocampal formation in healthy individuals: A diffusion tensor imaging study

NeuroImage

Volumn 89, Issue , 2014, Pages 256-261

  Dietsche, Bruno ^a   Backes, Heidelore ^a   Laneri, Davide ^a   Weikert, Thomas ^a   Witt, Stephanie H ^b   Rietschel, Marcella ^b   Sommer, Jens ^a   Kircher, Tilo ^a   Krug, Axel ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

CACNA1C; Diffusion tensor imaging; Hippocampal formation; Learning; White matter

Indexed keywords

ADULT; ALLELE; ARTICLE; CACNA1C GENE; CONTROLLED STUDY; DIFFUSION TENSOR IMAGING; FEMALE; FRACTIONAL ANISOTROPY; GENE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HIPPOCAMPUS; HUMAN; IMAGE ANALYSIS; LEARNING; LEARNING AND MEMORY TEST; MALE; NEUROIMAGING; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; GENETIC ASSOCIATION; HUMAN EXPERIMENT; LEARNING CURVE; MENTAL PERFORMANCE; NORMAL HUMAN; VERBAL MEMORY;

CACNA1C; DIFFUSION TENSOR IMAGING; HIPPOCAMPAL FORMATION; LEARNING; WHITE MATTER;

ADOLESCENT; ADULT; CALCIUM CHANNELS, L-TYPE; DIFFUSION TENSOR IMAGING; FEMALE; HIPPOCAMPUS; HUMANS; MALE; MEMORY; MIDDLE AGED; POLYMORPHISM, GENETIC; VERBAL LEARNING; YOUNG ADULT;

EID: 84892898782     PISSN: 10538119     EISSN: 10959572     Source Type: Journal    
DOI: 10.1016/j.neuroimage.2013.11.030     Document Type: Article

References (62)

1. Barnes A., Isohanni M., Barnett J.H., Pietiläinen O., Veijola J., Miettunen J., Paunio T., Tanskanen P., Ridler K., Suckling J., Bullmore E.T., Jones P.B., Murray G.K. Neuregulin-1 genotype is associated with structural differences in the normal human brain. Neuroimage 2012, 59:2057-2061.
2. Basser P.J., Jones D.K. Diffusion-tensor MRI: theory, experimental design and data analysis - a technical review. NMR Biomed. 2002, 15:456-467.
3. Bauer M., Alda M., Priller J., Young L.T., (IGSLI), I.G.F.T.S.O.L.T.P. Implications of the neuroprotective effects of lithium for the treatment of bipolar and neurodegenerative disorders. Pharmacopsychiatry 2003, 36:250-254.
4. Bhat S., Dao D.T., Terrillion C.E., Arad M., Smith R.J., Soldatov N.M., Gould T.D. CACNA1C (Ca(v)1.2) in the pathophysiology of psychiatric disease. Prog. Neurobiol. 2012, 99:1-14.
5. Bigos K.L., Mattay V.S., Callicott J.H., Straub R.E., Vakkalanka R., Kolachana B., Hyde T.M., Lipska B.K., Kleinman J.E., Weinberger D.R. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch. Gen. Psychiatry 2010, 67:939-945.
6. Bora E., Yucel M., Pantelis C. Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. Br. J. Psychiatry 2009, 195:475-482.
7. Cardno A.G., Gottesman I.I. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am. J. Med. Genet. 2000, 97:12-17.
8. Erk S., Meyer-Lindenberg A., Schnell K., Opitz von Boberfeld C., Esslinger C., Kirsch P., Grimm O., Arnold C., Haddad L., Witt S.H., Cichon S., Nöthen M.M., Rietschel M., Walter H. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch. Gen. Psychiatry 2010, 67:803-811.
9. Ferreira M.A., O'Donovan M.C., Meng Y.A., Jones I.R., Ruderfer D.M., Jones L., Fan J., Kirov G., Perlis R.H., Green E.K., Smoller J.W., Grozeva D., Stone J., Nikolov I., Chambert K., Hamshere M.L., Nimgaonkar V.L., Moskvina V., Thase M.E., Caesar S., Sachs G.S., Franklin J., Gordon-Smith K., Ardlie K.G., Gabriel S.B., Fraser C., Blumenstiel B., Defelice M., Breen G., Gill M., Morris D.W., Elkin A., Muir W.J., McGhee K.A., Williamson R., MacIntyre D.J., MacLean A.W., St C.D., Robinson M., Van Beck M., Pereira A.C., Kandaswamy R., McQuillin A., Collier D.A., Bass N.J., Young A.H., Lawrence J., Ferrier I.N., Anjorin A., Farmer A., Curtis D., Scolnick E.M., McGuffin P., Daly M.J., Corvin A.P., Holmans P.A., Blackwood D.H., Gurling H.M., Owen M.J., Purcell S.M., Sklar P., Craddock N., Consortium, W.T.C.C. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat. Genet. 2008, 40:1056-1058.
10. Fitzsimmons J., Kubicki M., Shenton M.E. Review of functional and anatomical brain connectivity findings in schizophrenia. Curr. Opin. Psychiatry 2013, 26:172-187.
11. Green E.K., Grozeva D., Jones I., Jones L., Kirov G., Caesar S., Gordon-Smith K., Fraser C., Forty L., Russell E., Hamshere M.L., Moskvina V., Nikolov I., Farmer A., McGuffin P., Holmans P.A., Owen M.J., O'Donovan M.C., Craddock N., Consortium, W.T.C.C. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol. Psychiatry 2010, 15:1016-1022.
12. Helmstaedter C., Lendt M., Lux S. Verbaler Lern- und Merkfähigkeitstest (VLMT) 2001, Hogrefe, Göttingen.
13. Hill S.K., Harris M.S., Herbener E.S., Pavuluri M., Sweeney J.A. Neurocognitive allied phenotypes for schizophrenia and bipolar disorder. Schizophr. Bull. 2008, 34:743-759.
14. Hori H., Yamamoto N., Fujii T., Teraishi T., Sasayama D., Matsuo J., Kawamoto Y., Kinoshita Y., Ota M., Hattori K., Tatsumi M., Arima K., Kunugi H. Effects of the CACNA1C risk allele on neurocognition in patients with schizophrenia and healthy individuals. Sci. Rep. 2012, 2:634.
15. Jogia J., Ruberto G., Lelli-Chiesa G., Vassos E., Maierú M., Tatarelli R., Girardi P., Collier D., Frangou S. The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Mol. Psychiatry 2011, 16:1070-1071.
16. Kempton M.J., Ruberto G., Vassos E., Tatarelli R., Girardi P., Collier D., Frangou S. Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals. Am. J. Psychiatry 2009, 166:1413-1414.
17. Konrad A., Vucurevic G., Musso F., Stoeter P., Dahmen N., Winterer G. ErbB4 genotype predicts left frontotemporal structural connectivity in human brain. Neuropsychopharmacology 2009, 34:641-650.
18. Krug A., Nieratschker V., Markov V., Krach S., Jansen A., Zerres K., Eggermann T., Stöcker T., Shah N.J., Treutlein J., Mühleisen T.W., Kircher T. Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage 2010, 49:1831-1836.
19. Krug A., Witt S.H., Backes H., Dietsche B., Nieratschker V., Shah N.J., Nöthen M.M., Rietschel M., Kircher T. A genome-wide supported variant in CACNA1C influences hippocampal activation during episodic memory encoding and retrieval. Eur. Arch. Psychiatry Clin. Neurosci. 2013, (Epub ahead of print). 10.1016/00406-013-0428-x.
20. Lacinova L., Moosmang S., Langwieser N., Hofmann F., Kleppisch T. Cav1.2 calcium channels modulate the spiking pattern of hippocampal pyramidal cells. Life Sci. 2008, 82:41-49.
21. Lee R.S., Hermens D.F., Porter M.A., Redoblado-Hodge M.A. A meta-analysis of cognitive deficits in first-episode major depressive disorder. J. Affect. Disord. 2012, 140:113-124.
22. Lehrl S., Triebig G., Fischer B. Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurol. Scand. 1995, 91:335-345.
23. Leitch B., Szostek A., Lin R., Shevtsova O. Subcellular distribution of L-type calcium channel subtypes in rat hippocampal neurons. Neuroscience 2009, 164:641-657.
24. Levinson D.F. The genetics of depression: a review. Biol. Psychiatry 2006, 60:84-92.
25. Liu Y., Blackwood D.H., Caesar S., de Geus E.J., Farmer A., Ferreira M.A., Ferrier I.N., Fraser C., Gordon-Smith K., Green E.K., Grozeva D., Gurling H.M., Hamshere M.L., Heutink P., Holmans P.A., Hoogendijk W.J., Hottenga J.J., Jones L., Jones I.R., Kirov G., Lin D., McGuffin P., Moskvina V., Nolen W.A., Perlis R.H., Posthuma D., Scolnick E.M., Smit A.B., Smit J.H., Smoller J.W., St Clair D., van Dyck R., Verhage M., Willemsen G., Young A.H., Zandbelt T., Boomsma D.I., Craddock N., O'Donovan M.C., Owen M.J., Penninx B.W., Purcell S., Sklar P., Sullivan P.F., Consortium, W.T.C.-C. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol. Psychiatry 2011, 16:2-4.
26. Matute C. Calcium dyshomeostasis in white matter pathology. Cell Calcium 2010, 47:150-157.
27. 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.
28. McIntosh A.M., Moorhead T.W., Job D., Lymer G.K., Muñoz Maniega S., McKirdy J., Sussmann J.E., Baig B.J., Bastin M.E., Porteous D., Evans K.L., Johnstone E.C., Lawrie S.M., Hall J. The effects of a neuregulin 1 variant on white matter density and integrity. Mol. Psychiatry 2008, 13:1054-1059.
29. Meyer-Lindenberg A., Weinberger D.R. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat. Rev. Neurosci. 2006, 7:818-827.
30. Moosmang S., Haider N., Klugbauer N., Adelsberger H., Langwieser N., Müller J., Stiess M., Marais E., Schulla V., Lacinova L., Goebbels S., Nave K.A., Storm D.R., Hofmann F., Kleppisch T. Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J. Neurosci. 2005, 25:9883-9892.
31. Moosmang S., Lenhardt P., Haider N., Hofmann F., Wegener J.W. Mouse models to study L-type calcium channel function. Pharmacol. Ther. 2005, 106:347-355.
32. Mori S. Introduction to Diffusion Tensor Imaging 2007, Elsevier BV, Amsterdam.
33. Moskvina V., Craddock N., Holmans P., Nikolov I., Pahwa J.S., Green E., Owen M.J., O'Donovan M.C., Consortium, W.T.C.C. Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. Mol. Psychiatry 2009, 14:252-260.
34. Nickl-Jockschat T., Stöcker T., Markov V., Krug A., Huang R., Schneider F., Habel U., Zerres K., Nöthen M.M., Treutlein J., Rietschel M., Shah N.J., Kircher T. The impact of a Dysbindin schizophrenia susceptibility variant on fiber tract integrity in healthy individuals: a TBSS-based diffusion tensor imaging study. Neuroimage 2012, 60:847-853.
35. Nyegaard M., Demontis D., Foldager L., Hedemand A., Flint T.J., Sørensen K.M., Andersen P.S., Nordentoft M., Werge T., Pedersen C.B., Hougaard D.M., Mortensen P.B., Mors O., Børglum A.D. CACNA1C (rs1006737) is associated with schizophrenia. Mol. Psychiatry 2010, 15:119-121.
36. Paulus F.M., Bedenbender J., Krach S., Pyka M., Krug A., Sommer J., Mette M., Nöthen M.M., Witt S.H., Rietschel M., Kircher T., Jansen A. Association of rs1006737 in CACNA1C with alterations in prefrontal activation and fronto-hippocampal connectivity. Hum. Brain Mapp 2013, (Epub ahead of print). 10.1002/hbm.22244.
37. Perrier E., Pompei F., Ruberto G., Vassos E., Collier D., Frangou S. Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder. Eur. Psychiatry 2011, 26:135-137.
38. Pettersson-Yeo W., Allen P., Benetti S., McGuire P., Mechelli A. Dysconnectivity in schizophrenia: where are we now?. Neurosci. Biobehav. Rev. 2011, 35:1110-1124.
39. Quraishi S., Walshe M., McDonald C., Schulze K., Kravariti E., Bramon E., Morris R.G., Murray R.M., Toulopoulou T. Memory functioning in familial bipolar I disorder patients and their relatives. Bipolar Disord. 2009, 11:209-214.
40. Radua J., Surguladze S.A., Marshall N., Walshe M., Bramon E., Collier D.A., Prata D.P., Murray R.M., McDonald C. The impact of CACNA1C allelic variation on effective connectivity during emotional processing in bipolar disorder. Mol. Psychiatry 2013, 18:526-527.
41. Ripke S., Sanders A.R., Kendler K.S., Levinson D.F., Sklar P., Holmans P.A., Lin D.Y., Duan J., Ophoff R.A., Andreassen O.A., Scolnick E., Cichon S., St Clair D., Corvin A., Gurling H., Werge T., Rujescu D., Blackwood D.H., Pato C.N., Malhotra A.K., Purcell S., Dudbridge F., Neale B.M., Rossin L., Visscher P.M., Posthuma D., Ruderfer D.M., Fanous A., Stefansson H., Steinberg S., Mowry B.J., Golimbet V., De Hert M., Jonsson E.G., Bitter I., Pietilainen O.P., Collier D.A., Tosato S., Agartz I., Albus M., Alexander M., Amdur R.L., Amin F., Bass N., Bergen S.E., Black D.W., Borglum A.D., Brown M.A., Bruggeman R., Buccola N.G., Byerley W.F., Cahn W., Cantor R.M., Carr V.J., Catts S.V., Choudhury K., Cloninger C.R., Cormican P., Craddock N., Danoy P.A., Datta S., de Haan L., Demontis D., Dikeos D., Djurovic S., Donnelly P., Donohoe G., Duong L., Dwyer S., Fink-Jensen A., Freedman R., Freimer N.B., Friedl M., Georgieva L., Giegling I., Gill M., Glenthoj B., Godard S., Hamshere M., Hansen M., Hansen T., Hartmann A.M., Henskens F.A., Hougaard D.M., Hultman C.M., Ingason A., Jablensky A.V., Jakobsen K.D., Jay M., Jurgens G., Kahn R.S., Keller M.C., Kenis G., Kenny E., Kim Y., Kirov G.K., Konnerth H., Konte B., Krabbendam L., Krasucki R., Lasseter V.K., Laurent C., Lawrence J., Lencz T., Lerer F.B., Liang K.Y., Lichtenstein P., Lieberman J.A., Linszen D.H., Lonnqvist J., Loughland C.M., Maclean A.W., Maher B.S., Maier W., Mallet J., Malloy P., Mattheisen M., Mattingsdal M., McGhee K.A., McGrath J.J., McIntosh A., McLean D.E., McQuillin A., Melle I., Michie P.T., Milanova V., Morris D.W., Mors O., Mortensen P.B., Moskvina V., Muglia P., Myin-Germeys I., Nertney D.A., Nestadt G., Nielsen J., Nikolov I., Nordentoft M., Norton N., Nothen M.M., O'Dushlaine C.T., Olincy A., Olsen L., O'Neill F.A., Orntoft T.F., Owen M.J., Pantelis C., Papadimitriou G., Pato M.T., Peltonen L., Petursson H., Pickard B., Pimm J., Pulver A.E., Puri V., Quested D., Quinn E.M., Rasmussen H.B., Rethelyi J.M., Ribble R., Rietschel M., Riley B.P., Ruggeri M., Schall U., Schulze T.G., Schwab S.G., Scott R.J., Shi J., Sigurdsson E., Silverman J.M., Spencer C.C., Stefansson K., Strange A., Strengman E., Stroup T.S., Suvisaari J., Terenius L., Thirumalai S., Thygesen J.H., Timm S., Toncheva D., van den Oord E., van Os J., van Winkel R., Veldink J., Walsh D., Wang A.G., Wiersma D., Wildenauer D.B., Williams H.J., Williams N.M., Wormley B., Zammit S., Sullivan P.F., O'Donovan M.C., Daly M.J., Gejman P.V., Schizophrenia Psychiatric Genome-Wide Association Study, C. Genome-wide association study identifies five new schizophrenia loci. Nat. Genet. 2011, 43:969-976.
42. Seidman L.J., Giuliano A.J., Meyer E.C., Addington J., Cadenhead K.S., Cannon T.D., McGlashan T.H., Perkins D.O., Tsuang M.T., Walker E.F., Woods S.W., Bearden C.E., Christensen B.K., Hawkins K., Heaton R., Keefe R.S., Heinssen R., Cornblatt B.A., Group, N.A.P.L.S.N. Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch. Gen. Psychiatry 2010, 67:578-588.
43. Sexton C.E., Mackay C.E., Ebmeier K.P. A systematic review of diffusion tensor imaging studies in affective disorders. Biol. Psychiatry 2009, 66:814-823.
44. Shi J., Potash J.B., Knowles J.A., Weissman M.M., Coryell W., Scheftner W.A., Lawson W.B., DePaulo J.R., Gejman P.V., Sanders A.R., Johnson J.K., Adams P., Chaudhury S., Jancic D., Evgrafov O., Zvinyatskovskiy A., Ertman N., Gladis M., Neimanas K., Goodell M., Hale N., Ney N., Verma R., Mirel D., Holmans P., Levinson D.F. Genome-wide association study of recurrent early-onset major depressive disorder. Mol. Psychiatry 2011, 16:193-201.
45. Sklar P., Smoller J.W., Fan J., Ferreira M.A., Perlis R.H., Chambert K., Nimgaonkar V.L., McQueen M.B., Faraone S.V., Kirby A., de Bakker P.I., Ogdie M.N., Thase M.E., Sachs G.S., Todd-Brown K., Gabriel S.B., Sougnez C., Gates C., Blumenstiel B., Defelice M., Ardlie K.G., Franklin J., Muir W.J., McGhee K.A., MacIntyre D.J., McLean A., VanBeck M., McQuillin A., Bass N.J., Robinson M., Lawrence J., Anjorin A., Curtis D., Scolnick E.M., Daly M.J., Blackwood D.H., Gurling H.M., Purcell S.M. Whole-genome association study of bipolar disorder. Mol. Psychiatry 2008, 13:558-569.
46. Smith S.M., Nichols T.E. Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 2009, 44:83-98.
47. Smith S.M., Jenkinson M., Johansen-Berg H., Rueckert D., Nichols T.E., Mackay C.E., Watkins K.E., Ciccarelli O., Cader M.Z., Matthews P.M., Behrens T.E. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006, 31:1487-1505.
48. Sprooten E., Sussmann J.E., Clugston A., Peel A., McKirdy J., Moorhead T.W., Anderson S., Shand A.J., Giles S., Bastin M.E., Hall J., Johnstone E.C., Lawrie S.M., McIntosh A.M. White matter integrity in individuals at high genetic risk of bipolar disorder. Biol. Psychiatry 2011, 70:350-356.
49. Sprooten E., Fleming K.M., Thomson P.A., Bastin M.E., Whalley H.C., Hall J., Sussmann J.E., McKirdy J., Blackwood D., Lawrie S.M., McIntosh A.M. White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiatry Res. 2013, 206:223-231.
50. Striessnig J., Koschak A., Sinnegger-Brauns M.J., Hetzenauer A., Nguyen N.K., Busquet P., Pelster G., Singewald N. Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem. Soc. Trans. 2006, 34:903-909.
51. Thimm M., Kircher T., Kellermann T., Markov V., Krach S., Jansen A., Zerres K., Eggermann T., Stöcker T., Shah N.J., Nöthen M.M., Rietschel M., Witt S.H., Mathiak K., Krug A. Effects of a CACNA1C genotype on attention networks in healthy individuals. Psychol. Med. 2011, 41:1551-1561.
52. Wang F., McIntosh A.M., He Y., Gelernter J., Blumberg H.P. The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord. 2011, 13:696-700.
53. Wang R., Ma Z., Wang J., Xie J. L-type Cav1.2 calcium channel is involved in 6-hydroxydopamine-induced neurotoxicity in rats. Neurotox. Res. 2012, 21:266-270.
54. Wessa M., Linke J., Witt S.H., Nieratschker V., Esslinger C., Kirsch P., Grimm O., Hennerici M.G., Gass A., King A.V., Rietschel M. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol. Psychiatry 2010, 15:1126-1127.
55. West A.E., Chen W.G., Dalva M.B., Dolmetsch R.E., Kornhauser J.M., Shaywitz A.J., Takasu M.A., Tao X., Greenberg M.E. Calcium regulation of neuronal gene expression. Proc. Natl. Acad. Sci. 2001, 98:11024-11031.
56. Wheeler D.G., Barrett C.F., Groth R.D., Safa P., Tsien R.W. CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling. J. Cell Biol. 2008, 183:849-863.
57. White J.A., McKinney B.C., John M.C., Powers P.A., Kamp T.J., Murphy G.G. Conditional forebrain deletion of the L-type calcium channel Ca V 1.2 disrupts remote spatial memories in mice. Learn. Mem. 2008, 15:1-5.
58. Whyte M.C., McIntosh A.M., Johnstone E.C., Lawrie S.M. Declarative memory in unaffected adult relatives of patients with schizophrenia: a systematic review and meta-analysis. Schizophr. Res. 2005, 78:13-26.
59. Winterer G., Konrad A., Vucurevic G., Musso F., Stoeter P., Dahmen N. Association of 5' end neuregulin-1 (NRG1) gene variation with subcortical medial frontal microstructure in humans. Neuroimage 2008, 40:712-718.
60. Wittchen H.-U., Wunderlich U., Gruschwitz S., Zaudig M. SKID-I. Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. Interviewheft 1997, Hogrefe, Göttingen.
61. Woodside B.L., Borroni A.M., Hammonds M.D., Teyler T.J. NMDA receptors and voltage-dependent calcium channels mediate different aspects of acquisition and retention of a spatial memory task. Neurobiol. Learn. Mem. 2004, 81:105-114.
62. Zhang Q., Shen Q., Xu Z., Chen M., Cheng L., Zhai J., Gu H., Bao X., Chen X., Wang K., Deng X., Ji F., Liu C., Li J., Dong Q., Chen C. The effects of CACNA1C gene polymorphism on spatial working memory in both healthy controls and patients with schizophrenia or bipolar disorder. Neuropsychopharmacology 2012, 37:677-684.