Linking neurodevelopmental and synaptic theories of mental illness through DISC1

Nature Reviews Neuroscience

Volumn 12, Issue 12, 2011, Pages

  Brandon, Nicholas J ^a   Sawa, Akira ^b  

^a PFIZER INC   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DISRUPTED IN SCHIZOPHRENIA 1 PROTEIN; DISC1 PROTEIN, HUMAN; NERVE PROTEIN;

CELL MIGRATION; CELL PROLIFERATION; CHROMOSOME TRANSLOCATION; ENDOPHENOTYPE; HIPPOCAMPUS; HUMAN; MENTAL DISEASE; NERVE CELL DIFFERENTIATION; NONHUMAN; PATHOPHYSIOLOGY; PEDIGREE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SYNAPSE; ANIMAL; BIOLOGICAL MODEL; BRAIN; CYTOLOGY; GENE EXPRESSION REGULATION; GENE TRANSLOCATION; GENETIC PREDISPOSITION; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PATHOLOGY;

ANIMALS; BRAIN; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MENTAL DISORDERS; MODELS, BIOLOGICAL; NERVE TISSUE PROTEINS; SYNAPSES; TRANSLOCATION, GENETIC;

EID: 81555203199     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn3120     Document Type: Review

References (200)

1. Philip, N. S., Carpenter, L. L., Tyrka, A. R. & Price, L. H. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin. Pharmacother. 11, 709-722 (2010).
2. Carter, C. S. & Barch, D. M. Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophr. Bull. 33, 1131-1137 (2007). (Pubitemid 47347921)
3. Green, M. F. et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol. Psychiatry 56, 301-307 (2004). (Pubitemid 39164514)
4. Kern, R. S., Glynn, S. M., Horan, W. P. & Marder, S. R. Psychosocial treatments to promote functional recovery in schizophrenia. Schizophr. Bull. 35, 347-361 (2009).
5. Kirkpatrick, B., Fenton, W. S., Carpenter, W. T. Jr & Marder, S. R. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr. Bull. 32, 214-219 (2006).
6. Meyer, J. M. Antipsychotic safety and efficacy concerns. J. Clin. Psychiatry 68, 20-26 (2007).
7. Meyer, J. M. Antipsychotics and metabolics in the post-CATIE era. Curr. Top. Behav. Neurosci. 4, 23-42 (2010).
8. Gartlehner, G. et al. Comparative risk for harms of second-generation antidepressants: a systematic review and meta-analysis. Drug Saf. 31, 851-865 (2008).
9. Williams, H. J., Owen, M. J. & O'Donovan, M. C. Schizophrenia genetics: new insights from new approaches. Br. Med. Bull. 91, 61-74 (2009).
10. Arenkiel, B. R. & Ehlers, M. D. Molecular genetics and imaging technologies for circuit-based neuroanatomy. Nature 461, 900-907 (2009).
11. Tsuang, M. Schizophrenia: genes and environment. Biol. Psychiatry 47, 210-220 (2000). (Pubitemid 30077397)
12. van Os, J., Kenis, G. & Rutten, B. P. The environment and schizophrenia. Nature 468, 203-212 (2010).
13. Moffitt, T. E., Caspi, A. & Rutter, M. Strategy for investigating interactions between measured genes and measured environments. Arch. Gen. Psychiatry 62, 473-481 (2005). (Pubitemid 40637222)
14. Owen, M. J., Craddock, N. & Jablensky, A. The genetic deconstruction of psychosis. Schizophr. Bull. 33, 905-911 (2007). (Pubitemid 47216654)
15. Cuthbert, B. & Insel, T. The data of diagnosis: new approaches to psychiatric classification. Psychiatry 73, 311-314 (2010).
16. Owen, M. J., O'Donovan, M. C., Thapar, A. & Craddock, N. Neurodevelopmental hypothesis of schizophrenia. Br. J. Psychiatry 198, 173-175 (2011).
17. Marenco, S. & Weinberger, D. R. The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave. Dev. Psychopathol. 12, 501-527 (2000).
18. Cannon, M., Jones, P. B. & Murray, R. M. Obstetric complications and schizophrenia: historical and meta-analytic review. Am. J. Psychiatry 159, 1080-1092 (2002). (Pubitemid 34743246)
19. Cannon, M. & Jones, P. Schizophrenia. J. Neurol. Neurosurg. Psychiatry 60, 604-613 (1996). (Pubitemid 26237110)
20. Powell, S. B. Models of neurodevelopmental abnormalities in schizophrenia. Curr. Top. Behav. Neurosci. 4, 435-481 (2010).
21. Jaaro-Peled, H. et al. Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1-ErbB4 and DISC1. Trends Neurosci. 32, 485-495 (2009).
22. Lewis, D. A., Hashimoto, T. & Volk, D. W. Cortical inhibitory neurons and schizophrenia. Nature Rev. Neurosci. 6, 312-324 (2005). (Pubitemid 40469985)
23. Goldman-Rakic, P. S. & Selemon, L. D. Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr. Bull. 23, 437-458 (1997). (Pubitemid 27427984)
24. Tamminga, C. A., Stan, A. D. & Wagner, A. D. The hippocampal formation in schizophrenia. Am. J. Psychiatry 167, 1178-1193 (2010).
25. Insel, T. R. Rethinking schizophrenia. Nature 468, 187-193 (2010).
26. St Clair, D. et al. Association within a family of a balanced autosomal translocation with major mental illness. Lancet 336, 13-16 (1990). (Pubitemid 20207869)
27. Muir, W. J., Pickard, B. S. & Blackwood, D. H. Disrupted-in- schizophrenia-1. Curr. Psychiatry Rep. 10, 140-147 (2008).
28. Jacobs, P. et al. Studies on a family with three cytogenetic markers. Ann. Hum. Genet. 33, 325-336 (1970).
29. Millar, J. K. et al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Mol. Genet. 9, 1415-1423 (2000). (Pubitemid 30312490)
30. Blackwood, D. H. et al. Schizophrenia and affective disorders- cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family. Am. J. Hum. Genet. 69, 428-433 (2001). (Pubitemid 32695214)
31. Hennah, W. et al. Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum. Mol. Genet. 12, 3151-3159 (2003). (Pubitemid 37508886)
32. Hamshere, M. L. et al. Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch. Gen. Psychiatry 62, 1081-1088 (2005). (Pubitemid 41396933)
33. Kilpinen, H. et al. Association of DISC1 with autism and Asperger syndrome. Mol. Psychiatry 13, 187-196 (2008).
34. Callicott, J. H. et al. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc. Natl Acad. Sci. USA 102, 8627-8632 (2005). (Pubitemid 40862786)
35. Hodgkinson, C. A. et al. Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am. J. Hum. Genet. 75, 862-872 (2004). (Pubitemid 39390493)
36. Hashimoto, R. et al. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum. Mol. Genet. 15, 3024-3033 (2006). (Pubitemid 44530706)
37. Song, W. et al. Identification of high risk DISC1 structural variants with a 2% attributable risk for schizophrenia. Biochem. Biophys. Res. Commun. 367, 700-706 (2008).
38. Song, W. et al. Identification of high risk DISC1 protein structural variants in patients with bipolar spectrum disorder. Neurosci. Lett. 486, 136-140 (2010).
39. Mathieson, I., Munafo, M. R. & Flint, J. Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophrenia. Mol. Psychiatry 12 Apr 2011 (doi:10.1038/mp.2011.41).
40. O'Donovan, M. C. et al. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genet. 40, 1053-1055 (2008).
41. Purcell, S. M. et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748-752 (2009).
42. Shi, J. et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 460, 753-757 (2009).
43. Stefansson, H. et al. Common variants conferring risk of schizophrenia. Nature 460, 744-747 (2009).
44. Sprooten, E. et al. Association of white matter integrity with genetic variation in an exonic DISC1 SNP. Mol. Psychiatry 16, 688-689 (2011).
45. Raznahan, A. et al. Common functional polymorphisms of DISC1 and cortical maturation in typically developing children and adolescents. Mol. Psychiatry 16, 917-926 (2011).
46. Blackwood, D. H. & Muir, W. J. Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia. Neurotox. Res. 6, 35-41 (2004).
47. Cannon, T. D. et al. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short-and long-term memory. Arch. Gen. Psychiatry 62, 1205-1213 (2005). (Pubitemid 41586920)
48. Hennah, W. et al. A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia. Mol. Psychiatry 10, 1097-1103 (2005). (Pubitemid 43251099)
49. Di Giorgio, A. et al. Association of the SerCys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding. Eur. J. Neurosci. 28, 2129-2136 (2008).
50. Szeszko, P. R. et al. DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia. Biol. Psychol. 79, 103-110 (2008).
51. Prata, D. P. et al. Effect of disrupted-in-schizophrenia-1 on pre-frontal cortical function. Mol. Psychiatry 13, 915-917, 909 (2008).
52. Carless, M. A. et al. Impact of DISC1 variation on neuroanatomical and neurocognitive phenotypes. Mol. Psychiatry. 12 Apr 2011 (doi:10.1038/mp.2011.37) .
53. Brauns, S. et al. DISC1 is associated with cortical thickness and neural efficiency. Neuroimage. 57, 1591-1600 (2011).
54. Takahashi, T. et al. The Disrupted-in-schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia. Psychiatry Res. 172, 128-135 (2009).
55. Mata, I. et al. Additive effect of NRG1 and DISC1 genes on lateral ventricle enlargement in first episode schizophrenia. Neuroimage 53, 1016-1022 (2010).
56. Tomppo, L. et al. Association of variants in DISC1 with psychosis-related traits in a large population cohort. Arch. Gen. Psychiatry 66, 134-141 (2009).
57. Merikangas, A. K., Corvin, A. P. & Gallagher, L. Copy-number variants in neurodevelopmental disorders: promises and challenges. Trends Genet. 25, 536-544 (2009).
58. Kim, Y., Zerwas, S., Trace, S. E. & Sullivan, P. F. Schizophrenia genetics: where next? Schizophr. Bull. 37, 456-463 (2011).
59. Schurov, I. L., Handford, E. J., Brandon, N. J. & Whiting, P. J. Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment. Mol. Psychiatry 9, 1100-1110 (2004). (Pubitemid 40065455)
60. Austin, C. P., Ky, B., Ma, L., Morris, J. A. & Shughrue, P. J. Expression of disrupted-in-schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development. Neuroscience 124, 3-10 (2004). (Pubitemid 38186612)
61. Seshadri, S. et al. Disrupted-in-schizophrenia-1 expression is regulated by β-site amyloid precursor protein cleaving enzyme-1-neuregulin cascade. Proc. Natl Acad. Sci. USA 107, 5622-5627 (2010).
62. Brandon, N. J. Dissecting DISC1 function through protein-protein interactions. Biochem. Soc. Trans. 35, 1283-1286 (2007). (Pubitemid 350206479)
63. Camargo, L. M. et al. Disrupted in schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol. Psychiatry 12, 74-86 (2007). (Pubitemid 44973664)
64. Morris, J. A., Kandpal, G., Ma, L. & Austin, C. P. DISC1 (disrupted-in-schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum. Mol. Genet. 12, 1591-1608 (2003). (Pubitemid 36857306)
65. Miyoshi, K. et al. Disrupted-in-schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Mol. Psychiatry 8, 685-694 (2003). (Pubitemid 36976300)
66. Ozeki, Y. et al. Disrupted-in-schizophrenia-1 (DISC-1): mutant truncation prevents binding to nudE-like (NUDEL) and inhibits neurite outgrowth. Proc. Natl Acad. Sci. USA 100, 289-294 (2003). (Pubitemid 36078067)
67. Millar, J. K., Christie, S. & Porteous, D. J. Yeast two-hybrid screens implicate DISC1 in brain development and function. Biochem. Biophys. Res. Commun. 311, 1019-1025 (2003). (Pubitemid 37393421)
68. Sawa, A. & Snyder, S. H. Genetics. Two genes link two distinct psychoses. Science 310, 1128-1129 (2005). (Pubitemid 41681728)
69. Ishizuka, K., Paek, M., Kamiya, A. & Sawa, A. A review of disrupted-in-schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions. Biol. Psychiatry 59, 1189-1197 (2006).
70. Porteous, D. J. & Millar, J. K. Disrupted in schizophrenia 1: building brains and memories. Trends Mol. Med. 12, 255-261 (2006). (Pubitemid 43870434)
71. Chubb, J. E., Bradshaw, N. J., Soares, D. C., Porteous, D. J. & Millar, J. K. The DISC locus in psychiatric illness. Mol. Psychiatry 13, 36-64 (2008).
72. Wang, Q., Jaaro-Peled, H., Sawa, A. & Brandon, N. J. How has DISC1 enabled drug discovery? Mol. Cell. Neurosci. 37, 187-195 (2008). (Pubitemid 351173852)
73. Brandon, N. J. et al. Understanding the role of DISC1 in psychiatric disease and during normal development. J. Neurosci. 29, 12768-12775 (2009).
74. Sawamura, N. & Sawa, A. Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major mental illnesses. Ann. N. Y. Acad. Sci. 1086, 126-133 (2006). (Pubitemid 47084386)
75. Brandon, N. J. et al. Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site. Mol. Cell. Neurosci. 28, 613-624 (2005). (Pubitemid 40387877)
76. Miyoshi, K. et al. DISC1 localizes to the centrosome by binding to kendrin. Biochem. Biophys. Res. Commun. 317, 1195-1199 (2004). (Pubitemid 38496437)
77. Wang, Q. & Brandon, N. J. Regulation of the cytoskeleton by disrupted-in-schizophrenia 1 (DISC1). Mol. Cell. Neurosci. 12 Jun 2011 (doi:10.1016/j. mcn.2011.06.004).
78. Kamiya, A. et al. A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development. Nature Cell Biol. 7, 1167-1178 (2005).
79. Dobyns, W. B., Reiner, O., Carrozzo, R. & Ledbetter, D. H. Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13. JAMA 270, 2838-2842 (1993). (Pubitemid 23361648)
80. Shu, T. et al. Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning. Neuron 44, 263-277 (2004). (Pubitemid 39346251)
81. Higginbotham, H. R. & Gleeson, J. G. The centrosome in neuronal development. Trends Neurosci. 30, 276-283 (2007). (Pubitemid 46802834)
82. Kamiya, A. et al. Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses. Arch. Gen. Psychiatry 65, 996-1006 (2008).
83. Datta, S. R. et al. A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia. Mol. Psychiatry 15, 615-628 (2010).
84. Gurling, H. M. et al. Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia. Arch. Gen. Psychiatry 63, 844-854 (2006). (Pubitemid 44188477)
85. Eastwood, S. L., Walker, M., Hyde, T. M., Kleinman, J. E. & Harrison, P. J. The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain. Hum. Mol. Genet. 19, 2487-2496 (2010).
86. Eastwood, S. L., Hodgkinson, C. A. & Harrison, P. J. DISC-1 Leu607Phe alleles differentially affect centrosomal PCM1 localization and neurotransmitter release. Mol. Psychiatry 14, 556-557 (2009).
87. Mao, Y. et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling. Cell 136, 1017-1031 (2009).
88. Shen, S. et al. Schizophrenia-related neural and behavioral phenotypes in transgenic mice expressing truncated Disc1. J. Neurosci. 28, 10893-10904 (2008).
89. Fukuda, T., Sugita, S., Inatome, R. & Yanagi, S. CAMDI, a novel disrupted in schizophrenia 1 (DISC1)-binding protein, is required for radial migration. J. Biol. Chem. 285, 40554-40561 (2010).
90. Singh, K. K. et al. Dixdc1 is a critical regulator of DISC1 and embryonic cortical development. Neuron 67, 33-48 (2010).
91. Ishizuka, K. et al. DISC1-dependent switch from progenitor proliferation to migration in the developing cortex. Nature 473, 92-96 (2011).
92. Lee, F. H. et al. Disc1 point mutations in mice affect development of the cerebral cortex. J. Neurosci. 31, 3197-3206 (2011).
93. Duan, X. et al. Disrupted-in-schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130, 1146-1158 (2007). (Pubitemid 47422304)
94. Kim, J. Y. et al. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 63, 761-773 (2009).
95. Enomoto, A. et al. Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. Neuron 63, 774-787 (2009).
96. Faulkner, R. L. et al. Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc. Natl Acad. Sci. USA 105, 14157-14162 (2008).
97. Tomita, K., Kubo, K. I., Ishii, K. & Nakajima, K. Disrupted-in-schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development. Hum. Mol. Genet. 20, 2834-2845 (2011).
98. Meyer, K. D. & Morris, J. A. Disc1 regulates granule cell migration in the developing hippocampus. Hum. Mol. Genet. 18, 3286-3297 (2009).
99. Kvajo, M. et al. A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proc. Natl Acad. Sci. USA 105, 7076-7081 (2008). (Pubitemid 351754532)
100. Namba, T. et al. NMDA receptor regulates migration of newly generated neurons in the adult hippocampus via disrupted-in-schizophrenia 1 (DISC1). J. Neurochem. 118, 34-44 (2011).
101. Fournier, N. M. et al. The effect of amygdala kindling on hippocampal neurogenesis coincides with decreased reelin and DISC1 expression in the adult dentate gyrus. Hippocampus 20, 659-671 (2010).
102. Penzes, P., Cahill, M. E., Jones, K. A., Vanleeuwen, J. E. & Woolfrey, K. M. Dendritic spine pathology in neuropsychiatric disorders. Nature Neurosci. 14, 285-293 (2011).
103. Blanpied, T. A. & Ehlers, M. D. Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease. Biol. Psychiatry 55, 1121-1127 (2004). (Pubitemid 38739445)
104. Tada, T. & Sheng, M. Molecular mechanisms of dendritic spine morphogenesis. Curr. Opin. Neurobiol. 16, 95-101 (2006). (Pubitemid 43221859)
105. Kasai, H., Fukuda, M., Watanabe, S., Hayashi-Takagi, A. & Noguchi, J. Structural dynamics of dendritic spines in memory and cognition. Trends Neurosci. 33, 121-129 (2010).
106. Shepherd, J. D. & Huganir, R. L. The cell biology of synaptic plasticity: AMPA receptor trafficking. Annu. Rev. Cell Dev. Biol. 23, 613-643 (2007).
107. Sheng, M. & Hoogenraad, C. C. The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu. Rev. Biochem. 76, 823-847 (2007).
108. Scannevin, R. H. & Huganir, R. L. Postsynaptic organization and regulation of excitatory synapses. Nature Rev. Neurosci. 1, 133-141 (2000).
109. Kirkpatrick, B. et al. DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex. J. Comp. Neurol. 497, 436-450 (2006). (Pubitemid 43865795)
110. Hayashi-Takagi, A. et al. Disrupted-in-schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nature Neurosci. 13, 327-332 (2010).
111. Wang, Q. et al. The psychiatric disease risk factors DISC1 and TNIK interact to regulate synapse composition and function. Mol. Psychiatry 16, 1006-1023 (2011).
112. Ramsey, A. J. et al. Impaired NMDA receptor transmission alters striatal synapses and DISC1 protein in an age-dependent manner. Proc. Natl Acad. Sci. USA 108, 5795-5800 (2011).
113. Clapcote, S. J. et al. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron 54, 387-402 (2007). (Pubitemid 46671409)
114. Makino, H. & Malinow, R. AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis. Neuron 64, 381-390 (2009).
115. Yang, Y., Wang, X. B., Frerking, M. & Zhou, Q. Delivery of AMPA receptors to perisynaptic sites precedes the full expression of long-term potentiation. Proc. Natl Acad. Sci. USA 105, 11388-11393 (2008).
116. Mohn, A. R., Gainetdinov, R. R., Caron, M. G. & Koller, B. H. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98, 427-436 (1999). (Pubitemid 29402481)
117. Hill, J. J., Hashimoto, T. & Lewis, D. A. Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia. Mol. Psychiatry 11, 557-566 (2006).
118. Ikeda, M. et al. Genome-wide association study of schizophrenia in a Japanese population. Biol. Psychiatry 69, 472-478 (2011).
119. Kushima, I. et al. Resequencing and association analysis of the KALRN and EPHB1 genes and their contribution to schizophrenia susceptibility. Schizophr. Bull. 1 Nov 2010 (doi:10.1093/schbul/sbq118).
120. Cahill, M. E. et al. Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proc. Natl Acad. Sci. USA 106, 13058-13063 (2009).
121. Penzes, P., Cahill, M. E., Jones, K. A. & Srivastava, D. P. Convergent CaMK and RacGEF signals control dendritic structure and function. Trends Cell Biol. 18, 405-413 (2008).
122. Penzes, P. & Jones, K. A. Dendritic spine dynamics-a key role for kalirin-7. Trends Neurosci. 31, 419-427 (2008).
123. Penzes, P. et al. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37, 263-274 (2003). (Pubitemid 36143821)
124. Xie, Z. et al. Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron 56, 640-656 (2007). (Pubitemid 350102031)
125. Cahill, M. E. et al. Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition. Mol. Psychiatry 12 Apr 2011 (doi:10.1038/mp.2011.35).
126. Harrison, P. J. & Law, A. J. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology. Biol. Psychiatry 60, 132-140 (2006).
127. Chen, S. Y., Huang, P. H. & Cheng, H. J. Disrupted-in-schizophrenia 1-mediated axon guidance involves TRIO-RAC-PAK small GTPase pathway signaling. Proc. Natl Acad. Sci. USA 108, 5861-5866 (2011).
128. Dan, I., Watanabe, N. M. & Kusumi, A. The Ste20 group kinases as regulators of MAP kinase cascades. Trends Cell Biol. 11, 220-230 (2001). (Pubitemid 32367879)
129. Fu, C. A. et al. TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. J. Biol. Chem. 274, 30729-30737 (1999).
130. Peng, J. et al. Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry. J. Biol. Chem. 279, 21003-21011 (2004). (Pubitemid 38656501)
131. Collins, M. O. et al. Proteomic analysis of in vivo phosphorylated synaptic proteins. J. Biol. Chem. 280, 5972-5982 (2005). (Pubitemid 40280081)
132. Potkin, S. G. et al. A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophr. Bull. 35, 96-108 (2009).
133. Hussain, N. K., Hsin, H., Huganir, R. L. & Sheng, M. MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J. Neurosci. 30, 14786-14794 (2010).
134. Mabb, A. M. & Ehlers, M. D. Ubiquitination in postsynaptic function and plasticity. Annu. Rev. Cell Dev. Biol. 26, 179-210 (2010).
135. Colledge, M. et al. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 40, 595-607 (2003). (Pubitemid 37494707)
136. Ehlers, M. D. Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting. Neuron 28, 511-525 (2000).
137. Rotin, D. & Kumar, S. Physiological functions of the HECT family of ubiquitin ligases. Nature Rev. Mol. Cell Biol. 10, 398-409 (2009).
138. Kawabe, H. & Brose, N. The ubiquitin E3 ligase Nedd4-1 controls neurite development. Cell Cycle 9, 2477-2478 (2010).
139. Schwarz, L. A., Hall, B. J. & Patrick, G. N. Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway. J. Neurosci. 30, 16718-16729 (2010).
140. Millar, J. K. et al. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310, 1187-1191 (2005). (Pubitemid 41681745)
141. Murdoch, H. et al. Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels. J. Neurosci. 27, 9513-9524 (2007). (Pubitemid 47358203)
142. Peineau, S. et al. LTP inhibits LTD in the hippocampus via regulation of GSK3β. Neuron 53, 703-717 (2007). (Pubitemid 46283369)
143. Gamo, N. J. et al. Knock-down of disrupted in schizophrenia 1 (DISC1) in the rat prefrontal cortex lowers the threshold for stress-induced cognitive dysfunction. 40th Ann. Meeting Soc. Neurosci. Abstr. (2010).
144. Brown, S. M. et al. Synaptic modulators Nrxn1 and Nrxn3 are disregulated in a Disc1 mouse model of schizophrenia. Mol. Psychiatry 16, 585-587 (2011).
145. Jaaro-Peled, H., Ayhan, Y., Pletnikov, M. V. & Sawa, A. Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr. Bull. 36, 301-313 (2010).
146. Kellendonk, C., Simpson, E. H. & Kandel, E. R. Modeling cognitive endophenotypes of schizophrenia in mice. Trends Neurosci. 32, 347-358 (2009).
147. Johnstone, M. et al. DISC1 in schizophrenia: genetic mouse models and human genomic imaging. Schizophr Bull. 37, 14-20 (2011).
148. Kelly, M. P. & Brandon, N. J. Taking a bird's eye view on a mouse model review: a comparison of findings from mouse models targeting DISC1 or DISC1-interacting proteins. Future Neurol. 6, 661-677 (2011).
149. Pletnikov, M. V. et al. Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia. Mol. Psychiatry 13, 173-186 (2008).
150. Hikida, T. et al. Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans. Proc. Natl Acad. Sci. USA 104, 14501-14506 (2007). (Pubitemid 350003290)
151. Li, W. et al. Specific developmental disruption of disrupted-in- schizophrenia-1 function results in schizophrenia-related phenotypes in mice. Proc. Natl Acad. Sci. USA 104, 18280-18285 (2007). (Pubitemid 350210858)
152. Koike, H., Arguello, P. A., Kvajo, M., Karayiorgou, M. & Gogos, J. A. Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice. Proc. Natl Acad. Sci. USA 103, 3693-3697 (2006). (Pubitemid 43376617)
153. Niwa, M. et al. Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits. Neuron 65, 480-489 (2010).
154. Pollak, D. D., Rey, C. E. & Monje, F. J. Rodent models in depression research: classical strategies and new directions. Ann. Med. 42, 252-264 (2010).
155. Van Snellenberg, J. X. & de Candia, T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch. Gen. Psychiatry 66, 748-755 (2009).
156. Ibi, D. et al. Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. Behav. Brain Res. 206, 32-37 (2010).
157. Abazyan, B. et al. Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biol. Psychiatry 68, 1172-1181 (2010).
158. Lipina, T. V. et al. Enhanced dopamine function in DISC1-L100P mutant mice: implications for schizophrenia. Genes Brain Behav. 9, 777-789 (2010).
159. Ayhan, Y. et al. Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders. Mol. Psychiatry 16, 293-306 (2011).
160. O'Donnell, P. Adolescent maturation of cortical dopamine. Neurotox. Res. 18, 306-312 (2010).
161. Lipina, T. V., Wang, M., Liu, F. & Roder, J. C. Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice. Neuropharmacology 2 Mar 2011 (doi:10.1016/j.neuropharm.2011.02.020).
162. Carlyle, B. C., Mackie, S., Christie, S., Millar, J. K. & Porteous, D. J. Co-ordinated action of DISC1, PDE4B and GSK3β in modulation of cAMP signalling. Mol. Psychiatry 16, 693-694 (2011).
163. Nakazawa, K. et al. GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 26 Jan 2011 (doi:10.1016/j. neuropharm.2011.01.022).
164. Jones, M. W. & Wilson, M. A. Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task. PLoS Biol. 3, e402 (2005).
165. Kubo, K. et al. Migration defects by DISC1 knockdown in C57BL/6, 129X1/SvJ, and ICR strains via in utero gene transfer and virus-mediated RNAi. Biochem. Biophys. Res. Commun. 400, 631-637 (2010).
166. Wood, J. D., Bonath, F., Kumar, S., Ross, C. A. & Cunliffe, V. T. Disrupted-in-schizophrenia 1 and neuregulin 1 are required for the specification of oligodendrocytes and neurones in the zebrafish brain. Hum. Mol. Genet. 18, 391-404 (2009).
167. Ottis, P. et al. Convergence of two independent mental disease genes on the protein level: recruitment of dysbindin to cell-invasive disrupted-in-schizophrenia 1 aggresomes. Biol. Psychiatry 70, 604-610 (2011).
168. Guo, A. Y. et al. The dystrobrevin-binding protein 1 gene: features and networks. Mol. Psychiatry 14, 18-29 (2009).
169. Ito, H. et al. Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Mol. Psychiatry 15, 976-986 (2010).
170. Dickman, D. K. & Davis, G. W. The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis. Science 326, 1127-1130 (2009).
171. Leliveld, S. R. et al. Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease. J. Neurosci. 28, 3839-3845 (2008).
172. Boxall, R., Porteous, D. J. & Thomson, P. A. DISC1 and Huntington's disease-overlapping pathways of vulnerability to neurological disorder? PLoS ONE 6, e16263 (2011).
173. Zhou, X., Chen, Q., Schaukowitch, K., Kelsoe, J. R. & Geyer, M. A. Insoluble DISC1-Boymaw fusion proteins generated by DISC1 translocation. Mol. Psychiatry 15, 669-672 (2010).
174. Zhou, X., Geyer, M. A. & Kelsoe, J. R. Does disrupted-in- schizophrenia (DISC1) generate fusion transcripts? Mol. Psychiatry 13, 361-363 (2008). (Pubitemid 351399822)
175. Millar, J. K., James, R., Christie, S. & Porteous, D. J. Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria. Mol. Cell. Neurosci. 30, 477-484 (2005). (Pubitemid 41721166)
176. MacAskill, A. F., Atkin, T. A. & Kittler, J. T. Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses. Eur. J. Neurosci. 32, 231-240 (2010).
177. MacAskill, A. F. & Kittler, J. T. Control of mitochondrial transport and localization in neurons. Trends Cell Biol. 20, 102-112 (2010).
178. Atkin, T. A., Macaskill, A. F., Brandon, N. J. & Kittler, J. T. Disrupted in schizophrenia-1 regulates intracellular trafficking of mitochondria in neurons. Mol. Psychiatry 16, 122-124 (2011).
179. Ikuta, J. et al. Fasciculation and elongation protein ζ-1 (FEZ1) participates in the polarization of hippocampal neuron by controlling the mitochondrial motility. Biochem. Biophys. Res. Commun. 353, 127-132 (2007). (Pubitemid 44958350)
180. Park, Y. U. et al. Disrupted-in-schizophrenia 1 (DISC1) plays essential roles in mitochondria in collaboration with Mitofilin. Proc. Natl Acad. Sci. USA 107, 17785-17790 (2010).
181. Sawamura, N. et al. Nuclear DISC1 regulates CRE-mediated gene transcription and sleep homeostasis in the fruit fly. Mol. Psychiatry 13, 1138-1148 (2008).
182. Drerup, C. M., Wiora, H. M., Topczewski, J. & Morris, J. A. Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development 136, 2623-2632 (2009).
183. Hattori, T. et al. DISC1 regulates cell-cell adhesion, cell-matrix adhesion and neurite outgrowth. Mol. Psychiatry 15, 778, 798-809 (2010).
184. Sawamura, N., Sawamura-Yamamoto, T., Ozeki, Y., Ross, C. A. & Sawa, A. A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse. Proc. Natl Acad. Sci. USA 102, 1187-1192 (2005). (Pubitemid 40170747)
185. Kamiya, A. et al. DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Hum. Mol. Genet. 15, 3313-3323 (2006). (Pubitemid 44642623)
186. Hayashi, M. A. et al. Assessing the role of endooligopeptidase activity of Ndel1 (nuclear-distribution gene E homolog like-1) in neurite outgrowth. Mol. Cell. Neurosci. 44, 353-361 (2010).
187. Hattori, T. et al. A novel DISC1-interacting partner DISC1-binding zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Mol. Psychiatry 12, 398-407 (2007). (Pubitemid 46496834)
188. Taylor, M. S., Devon, R. S., Millar, J. K. & Porteous, D. J. Evolutionary constraints on the disrupted in schizophrenia locus. Genomics 81, 67-77 (2003). (Pubitemid 36263360)
189. Ishizuka, K. et al. Evidence that many of the DISC1 isoforms in C57BL/56J mice are also expressed in 129S6/SvEv mice. Mol. Psychiatry 12, 897-899 (2007). (Pubitemid 47482699)
190. Meyer, K. D. & Morris, J. A. Immunohistochemical analysis of Disc1 expression in the developing and adult hippocampus. Gene Expr. Patterns 8, 494-501 (2008).
191. Lipina, T. V. et al. Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse 65, 234-248 (2011).
192. Young-Pearse, T. L., Suth, S., Luth, E. S., Sawa, A. & Selkoe, D. J. Biochemical and functional interaction of disrupted-in-schizophrenia 1 and amyloid precursor protein regulates neuronal migration during mammalian cortical development. J. Neurosci. 30, 10431-10440 (2010).
193. Shinoda, T. et al. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. J. Neurosci. 27, 4-14 (2007). (Pubitemid 46089954)
194. Taya, S. et al. DISC1 regulates the transport of the NUDEL/LIS1/14-3- 3epsilon complex through kinesin-1. J. Neurosci. 27, 15-26 (2007). (Pubitemid 46089955)
195. Nakata, K. et al. DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Proc. Natl Acad. Sci. USA 106, 15873-15878 (2009).
196. Brennand, K. J. et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221-225 (2011).
197. Sachs, N. A. et al. A frameshift mutation in disrupted in schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder. Mol. Psychiatry 10, 758-764 (2005). (Pubitemid 41129048)
198. Green, E. K. et al. Evidence that a DISC1 frame-shift deletion associated with psychosis in a single family may not be a pathogenic mutation. Mol. Psychiatry 11, 798-799 (2006). (Pubitemid 44299099)
199. Chiang, C. H. et al. Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol. Psychiatry 16, 358-360 (2011).
200. Brandon, N. J. et al. Disrupted in schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol. Cell. Neurosci. 25, 42-55 (2004). (Pubitemid 38220863)