What is the impact of genome-wide supported risk variants for schizophrenia and bipolar disorder on brain structure and function? A systematic review

Psychological Medicine

Volumn 45, Issue 12, 2015, Pages 2461-2480

  Gurung, R ^a   Prata, D P ^a,b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

Author keywords

ANK3; bipolar disorder; CACNA1C; DGKH; DTI; genome wide association; imaging genetics; intermediate phenotypes; MRI; NCAN; neuroimaging; NRGN; psychosis; review; schizophrenia; TCF4; ZNF804A

Indexed keywords

ANK3 PROTEIN, HUMAN; ANKYRIN; BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; CACNA1C PROTEIN, HUMAN; CALCIUM CHANNEL L TYPE; KRUPPEL LIKE FACTOR; LECTIN; NCAN PROTEIN, HUMAN; NERVE PROTEIN; NEUROGRANIN; NRGN PROTEIN, HUMAN; PROTEOCHONDROITIN SULFATE; TCF4 PROTEIN, HUMAN; TRANSCRIPTION FACTOR; ZNF804A PROTEIN, HUMAN;

BIPOLAR DISORDER; BRAIN; FEMALE; FUNCTIONAL NEUROIMAGING; GENE; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETICS; GENOME; GENOME-WIDE ASSOCIATION STUDY; HUMAN; MALE; MUTATION; PATHOPHYSIOLOGY; PHENOTYPE; PSYCHOLOGY; PSYCHOSIS; RISK FACTOR; SCHIZOPHRENIA;

ANKYRINS; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; BIPOLAR DISORDER; BRAIN; CALCIUM CHANNELS, L-TYPE; CHONDROITIN SULFATE PROTEOGLYCANS; FEMALE; FUNCTIONAL NEUROIMAGING; GENES; GENETIC PREDISPOSITION TO DISEASE; GENOME; GENOME-WIDE ASSOCIATION STUDY; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; LECTINS, C-TYPE; MALE; MUTATION; NERVE TISSUE PROTEINS; NEUROGRANIN; PHENOTYPE; POLYMORPHISM, GENETIC; PSYCHOTIC DISORDERS; RISK FACTORS; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; TRANSCRIPTION FACTORS;

EID: 84938744414     PISSN: 00332917     EISSN: 14698978     Source Type: Journal    
DOI: 10.1017/S0033291715000537     Document Type: Review

References (130)

1. Andreasen NC, Calarge CA, O'Leary DS. (2008). Theory of mind and schizophrenia: a positron emission tomography study of medication-free patients. Schizophrenia Bulletin 34, 708-719
2. Ansorge WJ. (2009). Next-generation DNA sequencing techniques. New Biotechnology 25, 195-203
3. Arseneault L, Cannon M, Witton J, Murray RM. (2004). Causal association between cannabis and psychosis: examination of the evidence. British Journal of Psychiatry 184, 110-117
4. Athanasiu L, Mattingsdal M, Kahler AK, Brown A, Gustafsson O, Agartz I, Giegling I, Muglia P, Cichon S, Rietschel M, Pietilainen OP, Peltonen L, Bramon E, Collier D, Clair DS, Sigurdsson E, Petursson H, Rujescu D, Melle I, Steen VM, Djurovic S, Andreassen OA. (2010). Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. Journal of Psychiatric Research 44, 748-753
5. Avissar S, Schreiber G. (2002). Toward molecular diagnostics of mood disorders in psychiatry. Trends in Molecular Medicine 8, 294-300
6. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels 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. Molecular Psychiatry 13, 197-107
7. Bebbington PE, Bhugra D, Brugha T, Singleton N, Farrell M, Jenkins R, Lewis G, Meltzer H. (2004). Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity. British Journal of Psychiatry 185, 220-226
8. Bergmann ø, Haukvik UK, Brown AA, Rimol LM, Hartberg CB, Athanasiu L, Melle I, Djurovic S, Andreassen OA, Dale AM, Agartz I. (2013). ZNF804A and cortical thickness in schizophrenia and bipolar disorder. Psychiatry Research: Neuroimaging 212, 154-157
9. Berridge MJ. (1989). The Albert Lasker Medical Awards. Inositol trisphosphate, calcium, lithium, and cell signaling. Journal of the American Medical Association 262, 1834-1841
10. 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. Archives of General Psychiatry 67, 939-945
11. Bora E, Yucel M, Pantelis C. (2009). Theory of mind impairment in schizophrenia: meta-Analysis. Schizophrenia Research 109, 1-9
12. Braff DL, Geyer MA, Swerdlow NR. (2001). Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 156, 234-258
13. Brennand KJ, Gage FH. (2011). Concise review: the promise of human induced pluripotent stem cell-based studies of schizophrenia. Stem Cells 29, 1915-1922
14. Brunet E, Sarfati Y, Hardy-Bayle MC, Decety J. (2003). Abnormalities of brain function during a nonverbal theory of mind task in schizophrenia. Neuropsychologia 41, 1574-1582
15. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafo MR. (2013). Power failure: why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience 14, 365-376
16. Calkins ME, Iacono WG. (2000). Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. American Journal of Medical Genetics 97, 72-76
17. Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR. (2000). Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cerebral Cortex 10, 1078-1092
18. Canals S, Beyerlein M, Merkle H, Logothetis NK. (2009). Functional MRI evidence for LTP-induced neural network reorganization. Current Biology 19, 398-403
19. Cannon M, Jones P. (1996). Schizophrenia. Journal of Neurology Neurosurgery and Psychiatry 60, 604-613
20. Canuso CM, Bossie CA, Zhu Y, Youssef E, Dunner DL. (2008). Psychotic symptoms in patients with bipolar mania. Journal of Affective Disorders 111, 164-169
21. Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM. (1999). Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Archives of General Psychiatry 56, 162-168
22. Carp J. (2012). The secret lives of experiments: methods reporting in the fMRI literature. Neuroimage 63, 289-300
23. Cichon S, Muhleisen TW, Degenhardt FA, Mattheisen M, Miro X, Strohmaier J, Steffens M, Meesters C, Herms S, Weingarten M, Priebe L, Haenisch B, Alexander M, Vollmer J, Breuer R, Schmal C, Tessmann P, Moebus S, Wichmann HE, Schreiber S, Muller-Myhsok B, Lucae S, Jamain S, Leboyer M, Bellivier F, Etain B, Henry C, Kahn JP, Heath S, Hamshere M, O'Donovan MC, Owen MJ, Craddock N, Schwarz M, Vedder H, Kammerer-Ciernioch J, Reif A, Sasse J, Bauer M, Hautzinger M, Wright A, Mitchell PB, Schofield PR, Montgomery GW, Medland SE, Gordon SD, Martin NG, Gustafsson O, Andreassen O, Djurovic S, Sigurdsson E, Steinberg S, Stefansson H, Stefansson K, Kapur-Pojskic L, Oruc L, Rivas F, Mayoral F, Chuchalin A, Babadjanova G, Tiganov AS, Pantelejeva G, Abramova LI, Grigoroiu-Serbanescu M, Diaconu CC, Czerski PM, Hauser J, Zimmer A, Lathrop M, Schulze TG, Wienker TF, Schumacher J, Maier W, Propping P, Rietschel M, Nothen MM. (2011). Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. American Journal of Human Genetics 88, 372-381
24. Cousijn H, Rijpkema M, Harteveld A, Harrison PJ, Fernandez G, Franke B, Arias-Vasquez A. (2012). Schizophrenia risk gene ZNF804A does not influence macroscopic brain structure: an MRI study in 892 volunteers. Molecular Psychiatry 17, 1155-1157
25. Cumming G. (2014). The new statistics: why and how. Psychological Science 25, 7-29
26. Curtis D, Vine AE, McQuillin A, Bass NJ, Pereira A, Kandaswamy R, Lawrence J, Anjorin A, Choudhury K, Datta SR, Puri V, Krasucki R, Pimm J, Thirumalai S, Quested D, Gurling HM. (2011). Case-case genome-wide association analysis shows markers differentially associated with schizophrenia and bipolar disorder and implicates calcium channel genes. Psychiatric Genetics 21, 1-4
27. Donohoe G, Rose E, Frodl T, Morris D, Spoletini I, Adriano F, Bernardini S, Caltagirone C, Bossu P, Gill M, Corvin AP, Spalletta G. (2011). ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia. Neuroimage 54, 2132-2137
28. Dudbridge F. (2013). Power and predictive accuracy of polygenic risk scores. PLoS Genetics 9, e1003348
29. Dudbridge F, Gusnanto A. (2008). Estimation of significance thresholds for genomewide association scans. Genetic Epidemiology 32, 227-234
30. 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, Nothen MM, Rietschel M, Walter H. (2010). Brain function in carriers of a genome-wide supported bipolar disorder variant. Archives of General Psychiatry 67, 803-811
31. Esslinger C, Kirsch P, Haddad L, Mier D, Sauer C, Erk S, Schnell K, Arnold C, Witt SH, Rietschel M, Cichon S, Walter H, Meyer-Lindenberg A. (2011). Cognitive state and connectivity effects of the genome-wide significant psychosis variant in ZNF804A. Neuroimage 54, 2514-2523
32. Esslinger C, Walter H, Kirsch P, Erk S, Schnell K, Arnold C, Haddad L, Mier D, Opitz von Boberfeld C, Raab K, Witt SH, Rietschel M, Cichon S, Meyer-Lindenberg A. (2009). Neural mechanisms of a genome-wide supported psychosis variant. Science 324, 605
33. Faravelli C, Guerrini Degl'Innocenti B, Aiazzi L, Incerpi G, Pallanti S. (1990). Epidemiology of mood disorders: a community survey in Florence. Journal of Affective Disorders 20, 135-141
34. Ferreira MA, 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, Hamshere ML, Nimgaonkar VL, Moskvina V, Thase ME, Caesar S, Sachs GS, Franklin J, Gordon-Smith K, Ardlie KG, Gabriel SB, Fraser C, Blumenstiel B, Defelice M, Breen G, Gill M, Morris DW, Elkin A, Muir WJ, McGhee KA, Williamson R, MacIntyre DJ, MacLean AW, St CD, Robinson M, Van Beck M, Pereira AC, Kandaswamy R, McQuillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Ferrier IN, Anjorin A, Farmer A, Curtis D, Scolnick EM, McGuffin P, Daly MJ, Corvin AP, Holmans PA, Blackwood DH, Gurling HM, Owen MJ, Purcell SM, Sklar P, Craddock N. (2008). Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nature Genetics 40, 1056-1058
35. Franke B, Vasquez AA, Veltman JA, Brunner HG, Rijpkema M, Fernandez G. (2010). Genetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals. Biological Psychiatry 68, 586-588
36. Friston K. (2012). Ten ironic rules for non-statistical reviewers. Neuroimage 61, 1300-1310
37. Girgenti MJ, LoTurco JJ, Maher BJ. (2012). ZNF804a regulates expression of the schizophrenia-Associated genes PRSS16, COMT, PDE4B, and DRD2. PLoS ONE 7, e32404
38. Gomez-Ospina N, Tsuruta F, Barreto-Chang O, Hu L, Dolmetsch R. (2006). The C terminus of the L-Type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor. Cell 127, 591-606
39. Gottesman II, Gould TD. (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636-645
40. Gottesman II, Laursen TM, Bertelsen A, Mortensen PB. (2010). Severe mental disorders in offspring with 2 psychiatrically ill parents. Archives of General Psychiatry 67, 252-257
41. Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Holmans PA, Owen MJ, O'Donovan MC, Craddock N. (2010). The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Molecular Psychiatry 15, 1016-1022
42. Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P, Wellcome Trust Case Control C, Holmans PA, Owen MJ, O'Donovan MC, Craddock N. (2010). The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Molecular Psychiatry 15, 1016-1022
43. Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR. (2002). The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage 17, 317-323
44. Haukvik UK, Saetre P, McNeil T, Bjerkan PS, Andreassen OA, Werge T, Jonsson EG, Agartz I. (2010). An exploratory model for G' E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 1259-1265
45. Hill MJ, Jeffries AR, Dobson RJ, Price J, Bray NJ. (2012). Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion. Human Molecular Genetics 21, 1018-1024
46. Hirschhorn JN, Daly MJ. (2005). Genome-wide association studies for common diseases and complex traits. Nature Reviews Genetics 6, 95-108
47. Hulshoff Pol HE, Schnack HG, Mandl RC, Brans RG, van Haren NE, Baare WF, van Oel CJ, Collins DL, Evans AC, Kahn RS. (2006). Gray and white matter density changes in monozygotic and same-sex dizygotic twins discordant for schizophrenia using voxel-based morphometry. Neuroimage 31, 482-488
48. Ioannidis JP. (2005). Why most published research findings are false. PLoS Medicine 2, e124
49. Jamison KR. (2000). Suicide and bipolar disorder. Journal of Clinical Psychiatry 61 (Suppl. 9), 47-51
50. Jogia J, Ruberto G, Lelli-Chiesa G, Vassos E, Maieru M, Tatarelli R, Girardi P, Collier D, Frangou S. (2011). The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Molecular Psychiatry 16, 1070-1071
51. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB. (2002). The long-Term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry 59, 530-537
52. Kempton MJ, Ruberto G, Vassos E, Tatarelli R, Girardi P, Collier D, Frangou S. (2009). Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals. American Journal of Psychiatry 166, 1413-1414
53. Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J. (2004). High concordance of bipolar I disorder in a nationwide sample of twins. American Journal of Psychiatry 161, 1814-1821
54. Kirkbride JB, Errazuriz A, Croudace TJ, Morgan C, Jackson D, Boydell J, Murray RM, Jones PB. (2012). Incidence of schizophrenia and other psychoses in England, 1950-2009: a systematic review and meta-Analyses. PloS One 7, e31660
55. Knapp M, Mangalore R, Simon J. (2004). The global costs of schizophrenia. Schizophrenia Bulletin 30, 279-293
56. Knight HM, Pickard BS, Maclean A, Malloy MP, Soares DC, McRae AF, Condie A, White A, Hawkins W, McGhee K, van Beck M, MacIntyre DJ, Starr JM, Deary IJ, Visscher PM, Porteous DJ, Cannon RE, St Clair D, Muir WJ, Blackwood DH. (2009). A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression. American Journal of Human Genetics 85, 833-846
57. Krug A, Krach S, Jansen A, Nieratschker V, Witt SH, Shah NJ, Nothen MM, Rietschel M, Kircher T. (2013). The effect of neurogranin on neural correlates of episodic memory encoding and retrieval. Schizophrenia Bulletin 39, 141-150
58. Krug A, Nieratschker V, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, Stocker T, Shah NJ, Treutlein J, Muhleisen TW, Kircher T. (2010). Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage 49, 1831-1836
59. Kurian SM, Le-Niculescu H, Patel SD, Bertram D, Davis J, Dike C, Yehyawi N, Lysaker P, Dustin J, Caligiuri M, Lohr J, Lahiri DK, Nurnberger JI Jr., Faraone SV, Geyer MA, Tsuang MT, Schork NJ, Salomon DR, Niculescu AB. (2011). Identification of blood biomarkers for psychosis using convergent functional genomics. Molecular Psychiatry 16, 37-58
60. Kuswanto CN, Woon PS, Zheng XB, Qiu A, Sitoh YY, Chan YH, Liu J, Williams H, Ong WY, Sim K. (2012). Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico-limbic WM integrity in schizophrenia. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 159B, 255-262
61. Lee KW, Woon PS, Teo YY, Sim K. (2012). Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt? Neuroscience & Biobehavioral Reviews 36, 556-571
62. Lencz T, Szeszko PR, DeRosse P, Burdick KE, Bromet EJ, Bilder RM, Malhotra AK. (2010). A schizophrenia risk gene, ZNF804A, influences neuroanatomical and neurocognitive phenotypes. Neuropsychopharmacology 35, 2284-2291
63. Li X, Branch CA, DeLisi LE. (2009). Language pathway abnormalities in schizophrenia: a review of fMRI and other imaging studies. Current Opinion in Psychiatry 22, 131-139
64. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234-239
65. Linden DE, Lancaster TM, Wolf C, Baird A, Jackson MC, Johnston SJ, Donev R, Thome J. (2013). ZNF804A genotype modulates neural activity during working memory for faces. Neuropsychobiology 67, 84-92
66. Linke J, Witt SH, King AV, Nieratschker V, Poupon C, Gass A, Hennerici MG, Rietschel M, Wessa M. (2012). Genome-wide supported risk variant for bipolar disorder alters anatomical connectivity in the human brain. Neuroimage 59, 3288-3296
67. Liu Y, Ray SK, Yang XQ, Luntz-Leybman V, Chiu IM. (1998). A splice variant of E2-2 basic helix-loop-helix protein represses the brain-specific fibroblast growth factor 1 promoter through the binding to an imperfect E-box. Journal of Biological Chemistry 273, 19269-19276
68. MacDonald AW III, Thermenos HW, Barch DM, Seidman LJ. (2009). Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives. Schizophrenia Bulletin 35, 1142-1162
69. Marwick K, Hall J. (2008). Social cognition in schizophrenia: a review of face processing. British Medical Bulletin 88, 43-58
70. McIntosh AM, Gow A, Luciano M, Davies G, Liewald DC, Harris SE, Corley J, Hall J, Starr JM, Porteous DJ, Tenesa A, Visscher PM, Deary IJ. (2013). Polygenic risk for schizophrenia is associated with cognitive change between childhood and old age. Biological Psychiatry 73, 938-943
71. Meyer-Lindenberg AS, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberger DR, Berman KF. (2005). Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Archives of General Psychiatry 62, 379-386
72. Miller GA, Chapman JP. (2001). Misunderstanding analysis of covariance. Journal of Abnormal Psychology 110, 40-48
73. Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370, 319-328
74. Mudge J, Miller NA, Khrebtukova I, Lindquist IE, May GD, Huntley JJ, Luo S, Zhang L, van Velkinburgh JC, Farmer AD, Lewis S, Beavis WD, Schilkey FD, Virk SM, Black CF, Myers MK, Mader LC, Langley RJ, Utsey JP, Kim RW, Roberts RC, Khalsa SK, Garcia M, Ambriz-Griffith V, Harlan R, Czika W, Martin S, Wolfinger RD, Perrone-Bizzozero NI, Schroth GP, Kingsmore SF. (2008). Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum. PLoS ONE 3, e3625
75. Murray CJ, Lopez AD. (1997). Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349, 1436-1442
76. Must A, Janka Z, Horvath S. (2011). Schizophrenia, environment and epigenetics [in Hungarian]. Neuropsychopharmacologia Hungarica 13, 211-217
77. Nelson MD, Saykin AJ, Flashman LA, Riordan HJ. (1998). Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-Analytic study. Archives of General Psychiatry 55, 433-440
78. Nicodemus KK, Callicott JH, Higier RG, Luna A, Nixon DC, Lipska BK, Vakkalanka R, Giegling I, Rujescu D, St Clair D, Muglia P, Shugart YY, Weinberger DR. (2010). Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging. Human Genetics 127, 441-452
79. Nicodemus KK, Law AJ, Radulescu E, Luna A, Kolachana B, Vakkalanka R, Rujescu D, Giegling I, Straub RE, McGee K, Gold B, Dean M, Muglia P, Callicott JH, Tan HY, Weinberger DR. (2010). Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls. Archives of General Psychiatry 67, 991-1001
80. Nyegaard M, Overgaard MT, Su YQ, Hamilton AE, Kwintkiewicz J, Hsieh M, Nayak NR, Conti M, Conover CA, Giudice LC. (2010). Lack of functional pregnancy-Associated plasma protein-A (PAPPA) compromises mouse ovarian steroidogenesis and female fertility. Biology of Reproduction 82, 1129-1138
81. O'Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, Dwyer S, Holmans P, Marchini JL, Spencer CC, Howie B, Leung HT, Hartmann AM, Moller HJ, Morris DW, Shi Y, Feng G, Hoffmann P, Propping P, Vasilescu C, Maier W, Rietschel M, Zammit S, Schumacher J, Quinn EM, Schulze TG, Williams NM, Giegling I, Iwata N, Ikeda M, Darvasi A, Shifman S, He L, Duan J, Sanders AR, Levinson DF, Gejman PV, Cichon S, Nothen MM, Gill M, Corvin A, Rujescu D, Kirov G, Owen MJ, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Cloninger CR. (2008). Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics 40, 1053-1055
82. Ogilvie AD, Morant N, Goodwin GM. (2005). The burden on informal caregivers of people with bipolar disorder. Bipolar Disorder 7 (Suppl. 1), 25-32
83. Ohi K, Hashimoto R, Yasuda Y, Nemoto K, Ohnishi T, Fukumoto M, Yamamori H, Umeda-Yano S, Okada T, Iwase M, Kazui H, TakedaM(2012). Impact of the genome wide supported NRGN gene on anterior cingulate morphology in schizophrenia. PLoS ONE 7, e29780
84. Paulus FM, Bedenbender J, Krach S, Pyka M, Krug A, Sommer J, Mette M, Nothen MM, Witt SH, Rietschel M, Kircher T, Jansen A. (2014). Association of rs1006737 in CACNA1C with alterations in prefrontal activation and fronto-hippocampal connectivity. Human Brain Mapping 35, 1190-1200
85. Paulus FM, Krach S, Bedenbender J, Pyka M, Sommer J, Krug A, Knake S, Nothen MM, Witt SH, Rietschel M, Kircher T, Jansen A. (2013). Partial support for ZNF804A genotype-dependent alterations in prefrontal connectivity. Human Brain Mapping 34, 304-313
86. Pelayo-Teran JM, Suarez-Pinilla P, Chadi N, Crespo-Facorro B. (2012). Gene-environment interactions underlying the effect of cannabis in first episode psychosis. Current Pharmaceutical Design 18, 5024-5035
87. Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E, Pirkola S, Partonen T, Tuulio-Henriksson A, Hintikka J, Kieseppa T. (2007). Lifetime prevalence of psychotic and bipolar I disorders in a general population. Archives of General Psychiatry 64, 19
88. Perrier E, Pompei F, Ruberto G, Vassos E, Collier D, Frangou S. (2011). Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder. European Psychiatry 26, 135-137
89. Petronis A, Gottesman II, Crow TJ, DeLisi LE, Klar AJ, Macciardi F, McInnis MG, McMahon FJ, Paterson AD, Skuse D, Sutherland GR. (2000). Psychiatric epigenetics: a new focus for the new century. Molecular Psychiatry 5, 342-346
90. Pohlack ST, Nees F, Ruttorf M, Witt SH, Nieratschker V, Rietschel M, Flor H. (2011). Risk variant for schizophrenia in the neurogranin gene impacts on hippocampus activation during contextual fear conditioning. Molecular Psychiatry 16, 1072-1073
91. Prata D, Mechelli A, Kapur S. (2014). Clinically meaningful biomarkers for psychosis: a systematic and quantitative review. Neuroscience and Biobehavioral Reviews 45, 134-141
92. Prata DP, Mechelli A, Fu CH, Picchioni M, Toulopoulou T, Bramon E, Walshe M, Murray RM, Collier DA, McGuire P. (2009). Epistasis between the DAT 3' UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia. Proceedings of the National Academy of Sciences USA 106, 13600-13605
93. Rasetti R, Mattay VS, Wiedholz LM, Kolachana BS, Hariri AR, Callicott JH, Meyer-Lindenberg A, Weinberger DR. (2009). Evidence that altered amygdala activity in schizophrenia is related to clinical state and not genetic risk. American Journal of Psychiatry 166, 216-225
94. Rasetti R, Sambataro F, Chen Q, Callicott JH, Mattay VS, Weinberger DR. (2011). Altered cortical network dynamics: a potential intermediate phenotype for schizophrenia and association with ZNF804A. Archives of General Psychiatry 68, 1207-1217
95. Rasetti R, Weinberger DR. (2011). Intermediate phenotypes in psychiatric disorders. Current Opinion in Genetics and Development 21, 340-348
96. Rose EJ, Morris DW, Fahey C, Robertson IH, Greene C, O'Doherty J, Newell FN, Garavan H, McGrath J, Bokde A, Tropea D, Gill M, Corvin AP, Donohoe G. (2012). The effect of the neurogranin schizophrenia risk variant rs12807809 on brain structure and function. Twin Research and Human Genetics 15, 296-303
97. Roussos P, Katsel P, Davis KL, Bitsios P, Giakoumaki SG, Jogia J, Rozsnyai K, Collier D, Frangou S, Siever LJ, Haroutunian V. (2012). Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia. Archives of General Psychiatry 69, 7-15
98. Russell TA, Rubia K, Bullmore ET, Soni W, Suckling J, Brammer MJ, Simmons A, Williams SC, Sharma T. (2000). Exploring the social brain in schizophrenia: left prefrontal underactivation during mental state attribution. American Journal of Psychiatry 157, 2040-2042
99. Schultz CC, Muhleisen TW, Nenadic I, Koch K, Wagner G, Schachtzabel C, Siedek F, Nothen MM, Rietschel M, Deufel T, Kiehntopf M, Cichon S, Reichenbach JR, Sauer H, Schlosser RG. (2014). Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia. Psychological Medicine 44, 811-820
100. Sims R, Hollingworth P, Moskvina V, Dowzell K, O'Donovan MC, Powell J, Lovestone S, Brayne C, Rubinsztein D, Owen MJ, Williams J, Abraham R. (2009). Evidence that variation in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene is associated with psychosis in Alzheimer's disease. Neuroscience Letters 461, 54-59
101. Soeiro-de-Souza MG, Otaduy MC, Dias CZ, Bio DS, Machado-Vieira R, Moreno RA. (2012). The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls. Journal of Affective Disorders 141, 94-101
102. Sprong M, Schothorst P, Vos E, Hox J, van Engeland H. (2007). Theory of mind in schizophrenia: meta-Analysis. British Journal of Psychiatry 191, 5-13
103. Sprooten E, McIntosh AM, Lawrie SM, Hall J, Sussmann JE, Dahmen N, Konrad A, Bastin ME, Winterer G. (2012). An investigation of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain. Magnetic Resonance Imaging 30, 1373-1380
104. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, Werge T, Pietilainen OP, Mors O, Mortensen PB, Sigurdsson E, Gustafsson O, Nyegaard M, Tuulio-Henriksson A, Ingason A, Hansen T, Suvisaari J, Lonnqvist J, Paunio T, Borglum AD, Hartmann A, Fink-Jensen A, Nordentoft M, Hougaard D, Norgaard-Pedersen B, Bottcher Y, Olesen J, Breuer R, Moller HJ, Giegling I, Rasmussen HB, Timm S, Mattheisen M, Bitter I, Rethelyi JM, Magnusdottir BB, Sigmundsson T, Olason P, Masson G, Gulcher JR, Haraldsson M, Fossdal R, Thorgeirsson TE, Thorsteinsdottir U, Ruggeri M, Tosato S, Franke B, Strengman E, Kiemeney LA, Melle I, Djurovic S, Abramova L, Kaleda V, Sanjuan J, de Frutos R, Bramon E, Vassos E, Fraser G, Ettinger U, Picchioni M, Walker N, Toulopoulou T, Need AC, Ge D, Yoon JL, Shianna KV, Freimer NB, Cantor RM, Murray R, Kong A, Golimbet V, Carracedo A, Arango C, Costas J, Jonsson EG, Terenius L, Agartz I, Petursson H, Nothen MM, Rietschel M, Matthews PM, Muglia P, Peltonen L, St Clair D, Goldstein DB, Stefansson K, Collier DA. (2009). Common variants conferring risk of schizophrenia. Nature 460, 744-747
105. Steinberg S, de Jong S, Irish Schizophrenia Genomics C, Andreassen OA, Werge T, Borglum AD, Mors O, Mortensen PB, Gustafsson O, Costas J, Pietilainen OP, Demontis D, Papiol S, Huttenlocher J, Mattheisen M, Breuer R, Vassos E, Giegling I, Fraser G, Walker N, Tuulio-Henriksson A, Suvisaari J, Lonnqvist J, Paunio T, Agartz I, Melle I, Djurovic S, Strengman E, Group, Jurgens G, Glenthoj B, Terenius L, Hougaard DM, Orntoft T, Wiuf C, Didriksen M, Hollegaard MV, Nordentoft M, van Winkel R, Kenis G, Abramova L, Kaleda V, Arrojo M, Sanjuan J, Arango C, Sperling S, Rossner M, Ribolsi M, Magni V, Siracusano A, Christiansen C, Kiemeney LA, Veldink J, van den Berg L, Ingason A, Muglia P, Murray R, Nothen MM, Sigurdsson E, Petursson H, Thorsteinsdottir U, Kong A, Rubino IA, De Hert M, Rethelyi JM, Bitter I, Jonsson EG, Golimbet V, Carracedo A, Ehrenreich H, Craddock N, Owen MJ, O'Donovan MC, Wellcome Trust Case Control C, Ruggeri M, Tosato S, Peltonen L, Ophoff RA, Collier DA, St Clair D, Rietschel M, Cichon S, Stefansson H, Rujescu D, Stefansson K. (2011). Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics 20, 4076-4081
106. Steinberg S, de Jong S, Mattheisen M, Costas J, Demontis D, Jamain S, Pietilainen OP, Lin K, Papiol S, Huttenlocher J, Sigurdsson E, Vassos E, Giegling I, Breuer R, Fraser G, Walker N, Melle I, Djurovic S, Agartz I, Tuulio-Henriksson A, Suvisaari J, Lonnqvist J, Paunio T, Olsen L, Hansen T, Ingason A, Pirinen M, Strengman E, Hougaard DM, Orntoft T, Didriksen M, Hollegaard MV, Nordentoft M, Abramova L, Kaleda V, Arrojo M, Sanjuan J, Arango C, Etain B, Bellivier F, Meary A, Schurhoff F, Szoke A, Ribolsi M, Magni V, Siracusano A, Sperling S, Rossner M, Christiansen C, Kiemeney LA, Franke B, van den Berg LH, Veldink J, Curran S, Bolton P, Poot M, Staal W, Rehnstrom K, Kilpinen H, Freitag CM, Meyer J, Magnusson P, Saemundsen E, Martsenkovsky I, Bikshaieva I, Martsenkovska I, Vashchenko O, Raleva M, Paketchieva K, Stefanovski B, Durmishi N, Pejovic Milovancevic M, Lecic Tosevski D, Silagadze T, Naneishvili N, Mikeladze N, Surguladze S, Vincent JB, Farmer A, Mitchell PB, Wright A, Schofield PR, Fullerton JM, Montgomery GW, Martin NG, Rubino IA, van Winkel R, Kenis G, De Hert M, Rethelyi JM, Bitter I, Terenius L, Jonsson EG, Bakker S, van Os J, Jablensky A, Leboyer M, Bramon E, Powell J, Murray R, Corvin A, Gill M, Morris D, O'Neill FA, Kendler K. (2014). Common variant at 16p11.2 conferring risk of psychosis. Molecular Psychiatry 19, 108-114
107. Stephan KE, Baldeweg T, Friston KJ. (2006). Synaptic plasticity and dysconnection in schizophrenia. Biological Psychiatry 59, 929-939
108. Szadoczky E, Papp Z, Vitrai J, Rihmer Z, Furedi J. (1998). The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey. Journal of Affective Disorders 50, 153-162
109. ten Have M, Vollebergh W, Bijl R, Nolen WA. (2002). Bipolar disorder in the general population in The Netherlands (prevalence, consequences and care utilisation): results from The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Journal of Affective Disorders 68, 203-213
110. Tesli M, Egeland R, Sonderby IE, Haukvik UK, Bettella F, Hibar DP, Thompson PM, Rimol LM, Melle I, Agartz I, Djurovic S, Andreassen OA. (2013). No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes. Journal of Affective Disorders 151, 291-297
111. Tesli M, Skatun KC, Ousdal OT, Brown AA, Thoresen C, Agartz I, Melle I, Djurovic S, Jensen J, Andreassen OA. (2013). CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls. PLoS ONE 8, e56970
112. Thimm M, Kircher T, Kellermann T, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, Stocker T, Shah NJ, Nothen MM, Rietschel M, Witt SH, Mathiak K, Krug A. (2011). Effects of a CACNA1C genotype on attention networks in healthy individuals. Psychological Medicine 41, 1551-1561
113. Thirion B, Pinel P, Meriaux S, Roche A, Dehaene S, Poline JB. (2007). Analysis of a large fMRI cohort: statistical and methodological issues for group analyses. Neuroimage 35, 105-120
114. Tohen M, Waternaux CM, Tsuang MT. (1990). Outcome in Mania. A 4-year prospective follow-up of 75 patients utilizing survival analysis. Archives of General Psychiatry 47, 1106-1111
115. Voineskos AN, Lerch JP, Felsky D, Tiwari A, Rajji TK, Miranda D, Lobaugh NJ, Pollock BG, Mulsant BH, Kennedy JL. (2011). The ZNF804A gene: characterization of a novel neural risk mechanism for the major psychoses. Neuropsychopharmacology 36, 1871-1878
116. Walter H, Schnell K, Erk S, Arnold C, Kirsch P, Esslinger C, Mier D, Schmitgen MM, Rietschel M, Witt SH, Nothen MM, Cichon S, Meyer-Lindenberg A. (2011). Effects of a genome-wide supported psychosis risk variant on neural activation during a theory-of-mind task. Molecular Psychiatry 16, 462-470
117. Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP. (2011). The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disorder 13, 696-700
118. Wassink TH, Epping EA, Rudd D, Axelsen M, Ziebell S, Fleming FW, Monson E, Ho BC, Andreasen NC. (2012). Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia. Archives of General Psychiatry 69, 885-892
119. Wei Q, Kang Z, Diao F, Guidon A, Wu X, Zheng L, Li L, Guo X, Hu M, Zhang J, Liu C, Zhao J. (2013). No association of ZNF804A rs1344706 with white matter integrity in schizophrenia: a tract-based spatial statistics study. Neuroscience Letters 532, 64-69
120. Wei Q, Kang Z, Diao F, Shan B, Li L, Zheng L, Guo X, Liu C, Zhang J, Zhao J. (2012). Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 36, 122-127
121. Weinberger DR. (1999). Cell biology of the hippocampal formation in schizophrenia. Biological Psychiatry 45, 395-402
122. Wessa M, Linke J, Witt SH, Nieratschker V, Esslinger C, Kirsch P, Grimm O, Hennerici MG, Gass A, King AV, Rietschel M. (2010). The CACNA1C risk variant for bipolar disorder influences limbic activity. Molecular Psychiatry 15, 1126-1127
123. Whalley HC, McKirdy J, Romaniuk L, Sussmann J, Johnstone EC, Wan HI, McIntosh AM, Lawrie SM, Hall J. (2009). Functional imaging of emotional memory in bipolar disorder and schizophrenia. Bipolar Disorder 11, 840-856
124. Whalley HC, Papmeyer M, Romaniuk L, Johnstone EC, Hall J, Lawrie SM, Sussmann JE, McIntosh AM. (2012). Effect of variation in diacylglycerol kinase eta (DGKH) gene on brain function in a cohort at familial risk of bipolar disorder. Neuropsychopharmacology 37, 919-928
125. Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S, Smith RL, Green E, Grozeva D, Holmans P, Owen MJ, O'Donovan MC. (2011). Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-Traditional diagnostic boundaries. Human Molecular Genetics 20, 387-391
126. Williams HJ, Norton N, Dwyer S, Moskvina V, Nikolov I, Carroll L, Georgieva L, Williams NM, Morris DW, Quinn EM, Giegling I, Ikeda M, Wood J, Lencz T, Hultman C, Lichtenstein P, Thiselton D, Maher BS, Malhotra AK, Riley B, Kendler KS, Gill M, Sullivan P, Sklar P, Purcell S, Nimgaonkar VL, Kirov G, Holmans P, Corvin A, Rujescu D, Craddock N, Owen MJ, O'Donovan MC. (2011). Fine mapping of ZNF804A and genomewide significant evidence for its involvement in schizophrenia and bipolar disorder. Molecular Psychiatry 16, 429-441
127. Wirgenes KV, Sonderby IE, Haukvik UK, Mattingsdal M, Tesli M, Athanasiu L, Sundet K, Rossberg JI, Dale AM, Brown AA, Agartz I, Melle I, Djurovic S, Andreassen OA. (2012). TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders. Transl Psychiatry 2, e112
128. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET. (2000). Meta-Analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16-25
129. Yang J, Lee SH, Goddard ME, Visscher PM. (2011) GCTA: a tool for genome-wide complex trait analysis. The American Journal of Human Genetics 88, 76-82
130. Yurgelun-Todd DA, Gruber SA, Kanayama G, Killgore WD, Baird AA, Young AD. (2000). fMRI during affect discrimination in bipolar affective disorder. Bipolar Disord 2, 237-248