Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2016 (2016), Article ID 2173748, 23 pages
http://dx.doi.org/10.1155/2016/2173748
Review Article

Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models

1School of Psychology, University of Nottingham, Nottingham NG7 2RD, UK
2School of Medicine, University College Cork, Brookfield Health Sciences Complex, College Road, Cork, Ireland
3School of Life Sciences, University of Glasgow, Room 220, Bower Building, Glasgow G12 8QQ, UK
4Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland
5Jiangsu Key Laboratory of Translational Research & Therapy for Neuropsychiatric Disorders and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China

Received 27 March 2016; Revised 20 July 2016; Accepted 21 August 2016

Academic Editor: Joram Feldon

Copyright © 2016 Paula Moran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. S. Brown, “Prenatal infection as a risk factor for schizophrenia,” Schizophrenia Bulletin, vol. 32, no. 2, pp. 200–202, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. A. S. Brown, “The environment and susceptibility to schizophrenia,” Progress in Neurobiology, vol. 93, no. 1, pp. 23–58, 2011. View at Publisher · View at Google Scholar · View at Scopus
  3. P. D. Harvey, A. P. Wingo, K. E. Burdick, and R. J. Baldessarini, “Cognition and disability in bipolar disorder: lessons from schizophrenia research,” Bipolar Disorders, vol. 12, no. 4, pp. 364–375, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. J. L. Waddington, R. J. Hennessy, C. M. P. O'Tuathaigh et al., “Schizophrenia and the lifetime trajectory of psychotic illness: developmental neuroscience and pathobiology, redux,” in The Origins of Schizophrenia, A. S. Brown and P. H. Patterson, Eds., pp. 3–21, Columbia University Press, New York, NY, USA, 2012. View at Google Scholar
  5. M. J. Owen, A. Sawa, and P. B. Mortensen, “Schizophrenia,” The Lancet, vol. 388, no. 10039, pp. 86–97, 2016. View at Publisher · View at Google Scholar
  6. A. Gustavsson, M. Svensson, F. Jacobi et al., “Cost of disorders of the brain in Europe 2010,” European Neuropsychopharmacology, vol. 21, no. 10, pp. 718–779, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. H. U. Wittchen, F. Jacobi, J. Rehm et al., “The size and burden of mental disorders and other disorders of the brain in Europe 2010,” European Neuropsychopharmacology, vol. 21, no. 9, pp. 655–679, 2011. View at Publisher · View at Google Scholar
  8. S. Leucht and S. Heres, “Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia,” Journal of Clinical Psychiatry, vol. 67, no. 5, pp. 3–8, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. P. J. Harrison, “Recent genetic findings in schizophrenia and their therapeutic relevance,” Journal of Psychopharmacology, vol. 29, no. 2, pp. 85–96, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. J. L. Rapoport, J. N. Giedd, and N. Gogtay, “Neurodevelopmental model of schizophrenia: update 2012,” Molecular Psychiatry, vol. 17, no. 12, pp. 1228–1238, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Gratten, N. R. Wray, M. C. Keller, and P. M. Visscher, “Large-scale genomics unveils the genetic architecture of psychiatric disorders,” Nature Neuroscience, vol. 17, no. 6, pp. 782–790, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Burmeister, “Basic concepts in the study of diseases with complex genetics,” Biological Psychiatry, vol. 45, no. 5, pp. 522–532, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Burmeister, M. G. McInnis, and S. Zöllner, “Psychiatric genetics: progress amid controversy,” Nature Reviews Genetics, vol. 9, no. 7, pp. 527–540, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Zammit, M. J. Owen, and G. Lewis, “Misconceptions about gene-environment interactions in psychiatry,” Evidence-Based Mental Health, vol. 13, no. 3, pp. 65–68, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. M. R. Munafò, S. Zammit, and J. Flint, “Practitioner Review: a critical perspective on gene-environment interaction models—what impact should they have on clinical perceptions and practice?” Journal of Child Psychology and Psychiatry and Allied Disciplines, vol. 55, no. 10, pp. 1092–1101, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. R. A. Shih, P. L. Belmonte, and P. P. Zandi, “A review of the evidence from family, twin and adoption studies for a genetic contribution to adult psychiatric disorders,” International Review of Psychiatry, vol. 16, no. 4, pp. 260–283, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. C. A. Prescott and I. I. Gottesman, “Genetically mediated vulnerability to schizophrenia,” Psychiatric Clinics of North America, vol. 16, no. 2, pp. 245–267, 1993. View at Google Scholar · View at Scopus
  18. M. S. Keshavan, “Development, disease and degeneration in schizophrenia: a unitary pathophysiological model,” Journal of Psychiatric Research, vol. 33, no. 6, pp. 513–521, 1999. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Tosato, P. Dazzan, and D. Collier, “Association between the neuregulin 1 gene and schizophrenia: a systematic review,” Schizophrenia Bulletin, vol. 31, no. 3, pp. 613–617, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. M. J. Owen, “Implications of genetic findings for understanding schizophrenia,” Schizophrenia Bulletin, vol. 38, no. 5, pp. 904–907, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. C. A. Ross, R. L. Margolis, S. A. J. Reading, M. Pletnikov, and J. T. Coyle, “Neurobiology of schizophrenia,” Neuron, vol. 52, no. 1, pp. 139–153, 2006. View at Publisher · View at Google Scholar · View at Scopus
  22. M. C. O'Donovan, N. J. Craddock, and M. J. Owen, “Genetics of psychosis; insights from views across the genome,” Human Genetics, vol. 126, no. 1, pp. 3–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. D. S. Rudd, M. Axelsen, E. A. Epping, N. C. Andreasen, and T. H. Wassink, “A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model,” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, vol. 165, no. 8, pp. 619–626, 2014. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Karl, “Neuregulin 1: a prime candidate for research into gene-environment interactions in schizophrenia? Insights from genetic rodent models,” Frontiers in Behavioral Neuroscience, vol. 7, article 106, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Kannan, A. Sawa, and M. V. Pletnikov, “Mouse models of gene-environment interactions in schizophrenia,” Neurobiology of Disease, vol. 57, pp. 5–11, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. C. M. O'Tuathaigh and J. L. Waddington, “Closing the translational gap between mutant mouse models and the clinical reality of psychotic illness,” Neuroscience and Biobehavioral Reviews, vol. 58, pp. 19–35, 2015. View at Publisher · View at Google Scholar · View at Scopus
  27. V. Labrie, S. Pai, and A. Petronis, “Epigenetics of major psychosis: progress, problems and perspectives,” Trends in Genetics, vol. 28, no. 9, pp. 427–435, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. Y. Ayhan, R. McFarland, and M. V. Pletnikov, “Animal models of gene-environment interaction in schizophrenia: a dimensional perspective,” Progress in Neurobiology, vol. 136, pp. 1–27, 2016. View at Publisher · View at Google Scholar · View at Scopus
  29. D. Malaspina, “Paternal factors and schizophrenia risk: de novo mutations and imprinting,” Schizophrenia Bulletin, vol. 27, no. 3, pp. 379–393, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Reichenberg, R. Gross, S. Sandin, and E. S. Susser, “Advancing paternal and maternal age are both important for autism risk,” American Journal of Public Health, vol. 100, no. 5, pp. 772–773, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Kong, M. L. Frigge, G. Masson et al., “Rate of de novo mutations and the importance of father’s age to disease risk,” Nature, vol. 488, no. 7412, pp. 471–475, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. M. C. Perrin, A. S. Brown, and D. Malaspina, “Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia,” Schizophrenia Bulletin, vol. 33, no. 6, pp. 1270–1273, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. R. G. Smith, A. Reichenberg, R. L. Kember et al., “Advanced paternal age is associated with altered DNA methylation at brain-expressed imprinted loci in inbred mice: implications for neuropsychiatric disease,” Molecular Psychiatry, vol. 18, no. 6, pp. 635–636, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. P. F. Sullivan, K. S. Kendler, and M. C. Neale, “Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies,” Archives of General Psychiatry, vol. 60, no. 12, pp. 1187–1192, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. International Schizophrenia Consortium, “Rare chromosomal deletions and duplications increase risk of schizophrenia,” Nature, vol. 455, pp. 237–241, 2008. View at Publisher · View at Google Scholar
  36. H. Stefansson, D. Rujescu, S. Cichon et al., “Large recurrent microdeletions associated with schizophrenia,” Nature, vol. 455, pp. 232–236, 2008. View at Publisher · View at Google Scholar
  37. G. Kirov, D. Rujescu, A. Ingason, D. A. Collier, M. C. O'Donovan, and M. J. Owen, “Neurexin 1 (NRXN1) deletions in schizophrenia,” Schizophrenia Bulletin, vol. 35, no. 5, pp. 851–854, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. P. V. Gejman, A. R. Sanders, and K. S. Kendler, “Genetics of schizophrenia: new findings and challenges,” Annual Review of Genomics and Human Genetics, vol. 12, pp. 121–144, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. Schizophrenia Working Group of the Psychiatric Genomics Consortium, “Biological insights from 108 schizophrenia-associated genetic loci,” Nature, vol. 511, pp. 421–427, 2014. View at Publisher · View at Google Scholar
  40. C. L. Winchester, J. A. Pratt, and B. J. Morris, “Risk genes for schizophrenia: translational opportunities for drug discovery,” Pharmacology and Therapeutics, vol. 143, no. 1, pp. 34–50, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. S. M. Purcell, J. L. Moran, M. Fromer et al., “A polygenic burden of rare disruptive mutations in schizophrenia,” Nature, vol. 506, no. 7487, pp. 185–190, 2014. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Hall, S. Trent, K. L. Thomas, M. C. O'Donovan, and M. J. Owen, “Genetic risk for schizophrenia: convergence on synaptic pathways involved in plasticity,” Biological Psychiatry, vol. 77, no. 1, pp. 52–58, 2015. View at Publisher · View at Google Scholar · View at Scopus
  43. Cross-Disorder Group of the Psychiatric Genomics Consortium, “Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs,” Nature Genetics, vol. 45, pp. 984–994, 2013. View at Google Scholar
  44. D. M. Ruderfer, A. H. Fanous, S. Ripke et al., “Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia,” Molecular Psychiatry, vol. 19, no. 9, pp. 1017–1024, 2014. View at Publisher · View at Google Scholar · View at Scopus
  45. S. A. McCarroll, G. Feng, and S. E. Hyman, “Genome-scale neurogenetics: methodology and meaning,” Nature Neuroscience, vol. 17, no. 6, pp. 756–763, 2014. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Cirulli, N. Francia, A. Berry, L. Aloe, E. Alleva, and S. J. Suomi, “Early life stress as a risk factor for mental health: role of neurotrophins from rodents to non-human primates,” Neuroscience and Biobehavioral Reviews, vol. 33, no. 4, pp. 573–585, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. E. J. Nestler and S. E. Hyman, “Animal models of neuropsychiatric disorders,” Nature Neuroscience, vol. 13, no. 10, pp. 1161–1169, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. J. van Os, G. Kenis, and B. P. F. Rutten, “The environment and schizophrenia,” Nature, vol. 468, no. 7321, pp. 203–212, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Gray and A. J. Hannan, “Dissecting cause and effect in the pathogenesis of psychiatric disorders: genes, environment and behaviour,” Current Molecular Medicine, vol. 7, no. 5, pp. 470–478, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. B. Abazyan, J. Nomura, G. Kannan et al., “Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology,” Biological Psychiatry, vol. 68, no. 12, pp. 1172–1181, 2010. View at Publisher · View at Google Scholar
  51. M. Niwa, R. S. Lee, T. Tanaka, K. Okada, S. Kano, and A. Sawa, “A critical period of vulnerability to adolescent stress: epigenetic mediators in mesocortical dopaminergic neurons,” Human Molecular Genetics, vol. 25, no. 7, pp. 1370–1381, 2016. View at Publisher · View at Google Scholar
  52. T. D. Cannon, T. G. M. Van Erp, C. E. Bearden et al., “Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions,” Schizophrenia Bulletin, vol. 29, no. 4, pp. 653–669, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. C. M. O'Tuathaigh, L. Desbonnet, P. M. Moran, and J. L. Waddington, “Susceptibility genes for schizophrenia: mutant models, endophenotypes and psychobiology,” Current Topics in Behavioural Neuroscience, vol. 12, pp. 209–250, 2012. View at Publisher · View at Google Scholar
  54. D. Braff, N. J. Schork, and I. I. Gottesman, “Endophenotyping schizophrenia,” American Journal of Psychiatry, vol. 164, no. 5, pp. 705–707, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. B. N. Cuthbert and T. R. Insel, “Toward the future of psychiatric diagnosis: the seven pillars of RDoC,” BMC Medicine, vol. 11, article 126, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. B. D. Kelly, E. O'Callaghan, J. L. Waddington et al., “Schizophrenia and the city: a review of literature and prospective study of psychosis and urbanicity in Ireland,” Schizophrenia Research, vol. 116, no. 1, pp. 75–89, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. P. Casadio, C. Fernandes, R. M. Murray, and M. Di Forti, “Cannabis use in young people: the risk for schizophrenia,” Neuroscience and Biobehavioral Reviews, vol. 35, no. 8, pp. 1779–1787, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. J. J. McGrath, M. R. Pemberton, J. L. Welham, and R. M. Murray, “Schizophrenia and the influenza epidemics of 1954, 1957 and 1959: a southern hemisphere study,” Schizophrenia Research, vol. 14, no. 1, pp. 1–8, 1994. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Cannon, D. Cotter, V. P. Coffey et al., “Prenatal exposure to the 1957 influenza epidemic and adult schizophrenia: a follow-up study,” British Journal of Psychiatry, vol. 168, pp. 368–371, 1996. View at Publisher · View at Google Scholar · View at Scopus
  60. P. B. Mortensen, C. B. Pedersen, T. Westergaard et al., “Effects of family history and place and season of birth on the risk of schizophrenia,” The New England Journal of Medicine, vol. 340, no. 8, pp. 603–608, 1999. View at Publisher · View at Google Scholar · View at Scopus
  61. S. L. Buka, T. D. Cannon, E. F. Torrey, and R. H. Yolken, “Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring,” Biological Psychiatry, vol. 63, no. 8, pp. 809–815, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. A. S. Brown and E. J. Derkits, “Prenatal infection and schizophrenia: a review of epidemiologic and translational studies,” The American Journal of Psychiatry, vol. 167, no. 3, pp. 261–280, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. U. Meyer, J. Feldon, M. Schedlowski, and B. K. Yee, “Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia,” Neuroscience and Biobehavioral Reviews, vol. 29, no. 6, pp. 913–947, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. U. Meyer, J. Feldon, M. Schedlowski, and B. K. Yee, “Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology,” Brain, Behavior, and Immunity, vol. 20, no. 4, pp. 378–388, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. U. Meyer, P. J. Murray, A. Urwyler, B. K. Yee, M. Schedlowski, and J. Feldon, “Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling,” Molecular Psychiatry, vol. 13, no. 2, pp. 208–221, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. B. K. Bitanihirwe, D. Peleg-Raibstein, F. Mouttet, J. Feldon, and U. Meyer, “Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia,” Neuropsychopharmacology, vol. 35, no. 12, pp. 2462–2478, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Shi, S. H. Fatemi, R. W. Sidwell, and P. H. Patterson, “Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring,” The Journal of Neuroscience, vol. 23, no. 1, pp. 297–302, 2003. View at Google Scholar · View at Scopus
  68. U. Meyer, M. Nyffeler, A. Engler et al., “The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology,” The Journal of Neuroscience, vol. 26, no. 18, pp. 4752–4762, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. L. Zuckerman, M. Rehavi, R. Nachman, and I. Weiner, “Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia,” Neuropsychopharmacology, vol. 28, no. 10, pp. 1778–1789, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. S. E. P. Smith, J. Li, K. Garbett, K. Mirnics, and P. H. Patterson, “Maternal immune activation alters fetal brain development through interleukin-6,” The Journal of Neuroscience, vol. 27, no. 40, pp. 10695–10702, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. N. V. Malkova, C. Z. Yu, E. Y. Hsiao, M. J. Moore, and P. H. Patterson, “Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism,” Brain, Behavior, and Immunity, vol. 26, no. 4, pp. 607–616, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. L. Zuckerman and I. Weiner, “Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation,” Psychopharmacology, vol. 169, no. 3-4, pp. 308–313, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Zavitsanou, C. K. Lim, T. Purves-Tyson et al., “Effect of maternal immune activation on the kynurenine pathway in preadolescent rat offspring and on MK801-induced hyperlocomotion in adulthood: amelioration by COX-2 inhibition,” Brain, Behavior, and Immunity, vol. 41, no. 1, pp. 173–181, 2014. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Piontkewitz, M. Arad, and I. Weiner, “Abnormal trajectories of neurodevelopment and behavior following in utero insult in the rat,” Biological Psychiatry, vol. 70, no. 9, pp. 842–851, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. S. Reisinger, D. Khan, E. Kong, A. Berger, A. Pollak, and D. D. Pollak, “The Poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery,” Pharmacology and Therapeutics, vol. 149, pp. 213–226, 2015. View at Publisher · View at Google Scholar · View at Scopus
  76. H. Stefansson, E. Sigurdsson, V. Steinthorsdottir et al., “Neuregulin 1 and susceptibility to schizophrenia,” American Journal of Human Genetics, vol. 71, no. 4, pp. 877–892, 2002. View at Publisher · View at Google Scholar · View at Scopus
  77. Y. G. Gong, C. N. Wu, Q. H. Xing, X. Z. Zhao, J. Zhu, and L. He, “A two-method meta-analysis of Neuregulin 1(NRG1) association and heterogeneity in schizophrenia,” Schizophrenia Research, vol. 111, no. 1–3, pp. 109–114, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. H. C. Loh, P. Y. Tang, S. F. Tee et al., “Neuregulin-1 (NRG-1) and its susceptibility to schizophrenia: a case-control study and meta-analysis,” Psychiatry Research, vol. 208, no. 2, pp. 186–188, 2013. View at Publisher · View at Google Scholar · View at Scopus
  79. P. J. Harrison and A. J. Law, “Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology,” Biological Psychiatry, vol. 60, no. 2, pp. 132–140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Mei and W.-C. Xiong, “Neuregulin 1 in neural development, synaptic plasticity and schizophrenia,” Nature Reviews Neuroscience, vol. 9, no. 6, pp. 437–452, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. K. Hänninen, H. Katila, M. Saarela et al., “Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia,” European Archives of Psychiatry and Clinical Neuroscience, vol. 258, no. 1, pp. 10–15, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. K. Marballi, M. P. Quinones, F. Jimenez et al., “In vivo and in vitro genetic evidence of involvement of neuregulin 1 in immune system dysregulation,” Journal of Molecular Medicine, vol. 88, no. 11, pp. 1133–1141, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. T. Kato, A. Kasai, M. Mizuno et al., “Phenotypic characterization of transgenic mice overexpressing neuregulin-1,” PLoS ONE, vol. 5, no. 12, Article ID e14185, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Karl, L. Duffy, A. Scimone, R. P. Harvey, and P. R. Schofield, “Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia,” Genes, Brain and Behavior, vol. 6, no. 7, pp. 677–687, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. C. M. P. O'Tuathaigh, D. Babovic, G. J. O'Sullivan et al., “Phenotypic characterization of spatial cognition and social behavior in mice with ‘knockout’ of the schizophrenia risk gene neuregulin 1,” Neuroscience, vol. 147, no. 1, pp. 18–27, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. L. Desbonnet, C. O'Tuathaigh, G. Clarke et al., “Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: a putative model of gene × environment interaction,” Brain, Behavior, and Immunity, vol. 26, no. 4, pp. 660–671, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. M. van den Buuse, L. Wischhof, R. X. Lee, S. Martin, and T. Karl, “Neuregulin 1 hypomorphic mutant mice: enhanced baseline locomotor activity but normal psychotropic drug-induced hyperlocomotion and prepulse inhibition regulation,” International Journal of Neuropsychopharmacology, vol. 12, no. 10, pp. 1383–1393, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. T. Karl, T. H. J. Burne, M. Van den Buuse, and R. Chesworth, “Do transmembrane domain neuregulin 1 mutant mice exhibit a reliable sensorimotor gating deficit?” Behavioural Brain Research, vol. 223, no. 2, pp. 336–341, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. M. Rimer, D. W. Barrett, M. A. Maldonado, V. M. Vock, and F. Gonzalez-Lima, “Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition,” NeuroReport, vol. 16, no. 3, pp. 271–275, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. Y.-J. J. Chen, M. A. Johnson, M. D. Lieberman et al., “Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components,” The Journal of Neuroscience, vol. 28, no. 27, pp. 6872–6883, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. J.-C. Pei, C.-M. Liu, and W.-S. Lai, “Distinct phenotypes of new transmembrane-domain neuregulin 1 mutant mice and the rescue effects of valproate on the observed schizophrenia-related cognitive deficits,” Frontiers in Behavioral Neuroscience, vol. 8, article 126, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. C. O'Leary, L. Desbonnet, N. Clarke et al., “Phenotypic effects of maternal immune activation and early postnatal milieu in mice mutant for the schizophrenia risk gene neuregulin-1,” Neuroscience, vol. 277, pp. 294–305, 2014. View at Publisher · View at Google Scholar · View at Scopus
  93. D. H. R. Blackwood, A. Fordyce, M. T. Walker, D. M. St. Clair, D. J. Porteous, and W. J. Muir, “Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family,” American Journal of Human Genetics, vol. 69, no. 2, pp. 428–433, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. N. A. Sachs, A. Sawa, S. E. Holmes, C. A. Ross, L. E. DeLisi, and R. L. Margolis, “A frameshift mutation in disrupted in schizophrenia 1 in an American family with schizophrenia and schizoaffective disorder,” Molecular Psychiatry, vol. 10, no. 8, pp. 758–764, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. N. J. Bradshaw and D. J. Porteous, “DISC1-binding proteins in neural development, signalling and schizophrenia,” Neuropharmacology, vol. 62, no. 3, pp. 1230–1241, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. N. J. Brandon and A. Sawa, “Linking neurodevelopmental and synaptic theories of mental illness through DISC1,” Nature Reviews Neuroscience, vol. 12, no. 12, pp. 707–722, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. S. J. Clapcote, T. V. Lipina, J. K. Millar et al., “Behavioral phenotypes of Disc1 missense mutations in mice,” Neuron, vol. 54, no. 3, pp. 387–402, 2007. View at Publisher · View at Google Scholar · View at Scopus
  98. T. Hikida, H. Jaaro-Peled, S. Seshadri et al., “Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 36, pp. 14501–14506, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. W. Li, Y. Zhou, J. D. Jentsch et al., “Specific developmental disruption of disrupted-in-schizophrenia-1 function results in schizophrenia-related phenotypes in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 46, pp. 18280–18285, 2007. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Kvajo, H. McKellar, P. A. Arguello et al., “A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 19, pp. 7076–7081, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. M. V. Pletnikov, Y. Ayhan, O. Nikolskaia et al., “Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia,” Molecular Psychiatry, vol. 13, no. 2, pp. 173–186, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. S. Shen, B. Lang, C. Nakamoto et al., “Schizophrenia-related neural and behavioral phenotypes in transgenic mice expressing truncated DISC1,” The Journal of Neuroscience, vol. 28, no. 43, pp. 10893–10904, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. Y. Mao, X. Ge, C. L. Frank et al., “Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling,” Cell, vol. 136, no. 6, pp. 1017–1031, 2009. View at Publisher · View at Google Scholar · View at Scopus
  104. T. V. Lipina, C. Zai, D. Hlousek, J. C. Roder, and A. H. C. Wong, “Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice,” The Journal of Neuroscience, vol. 33, no. 18, pp. 7654–7666, 2013. View at Publisher · View at Google Scholar · View at Scopus
  105. D. Ibi, T. Nagai, Y. Kitahara et al., “Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood,” Neuroscience Research, vol. 64, no. 3, pp. 297–305, 2009. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Nagai, Y. Kitahara, D. Ibi, T. Nabeshima, A. Sawa, and K. Yamada, “Effects of antipsychotics on the behavioral deficits in human dominant-negative DISC1 transgenic mice with neonatal polyI:C treatment,” Behavioural Brain Research, vol. 225, no. 1, pp. 305–310, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. B. Abazyan, J. Dziedzic, K. Hua et al., “Chronic exposure of mutant DISC1 mice to lead produces sex-dependent abnormalities consistent with schizophrenia and related mental disorders: a gene-environment interaction study,” Schizophrenia Bulletin, vol. 40, no. 3, pp. 575–584, 2014. View at Publisher · View at Google Scholar · View at Scopus
  108. B. Kadkhodaei, T. Ito, E. Joodmardi et al., “Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons,” The Journal of Neuroscience, vol. 29, no. 50, pp. 15923–15932, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. P. Rojas, E. Joodmardi, Y. Hong, T. Perlmann, and S. O. Ögren, “Adult mice with reduced Nurr1 expression: an animal model for schizophrenia,” Molecular Psychiatry, vol. 12, no. 8, pp. 756–766, 2007. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Vuillermot, E. Joodmardi, T. Perlmann, S. O. Ögren, J. Feldon, and U. Meyer, “Prenatal immune activation interacts with genetic Nurr1 deficiency in the development of attentional impairments,” The Journal of Neuroscience, vol. 32, no. 2, pp. 436–451, 2012. View at Publisher · View at Google Scholar · View at Scopus
  111. B. Hibell, U. Guttormsson, S. Ahlström et al., The 2011 ESPAD Report. Substance Use Among Students in 36 European Countries, The Swedish Council for Information on Alcohol and Other Drugs (CAN), Stockholm, Sweden, 2012.
  112. L. D. Johnston, P. M. O'Malley, J. G. Bachman et al., Monitoring the Future National Survey Results on Drug Use, 1975–2013: Volume I, Secondary School Students, Institute for Social Research, The University of Michigan, Ann Arbor, Mich, USA, 2014.
  113. D. Linszen and T. van Amelsvoort, “Cannabis and psychosis: an update on course and biological plausible mechanisms,” Current Opinion in Psychiatry, vol. 20, no. 2, pp. 116–120, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. T. H. Moore, S. Zammit, A. Lingford-Hughes et al., “Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review,” The Lancet, vol. 370, no. 9584, pp. 319–328, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. D. M. Fergusson, L. J. Horwood, and N. R. Swain-Campbell, “Cannabis dependence and psychotic symptoms in young people,” Psychological Medicine, vol. 33, no. 1, pp. 15–21, 2003. View at Publisher · View at Google Scholar · View at Scopus
  116. L. Arseneault, M. Cannon, R. Poulton, R. Murray, A. Caspi, and T. E. Moffitt, “Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study,” British Medical Journal, vol. 325, no. 7374, pp. 1212–1213, 2002. View at Publisher · View at Google Scholar · View at Scopus
  117. L. Arseneault, M. Cannon, J. Witton, and R. M. Murray, “Causal association between cannabis and psychosis: examination of the evidence,” British Journal of Psychiatry, vol. 184, pp. 110–117, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. J. McGrath, J. Welham, J. Scott et al., “Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults,” Archives of General Psychiatry, vol. 67, no. 5, pp. 440–447, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. J. Decoster, J. van Os, I. Myin-Germeys, M. De Hert, and R. van Winkel, “Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions,” Current Pharmaceutical Design, vol. 18, no. 32, pp. 5015–5023, 2012. View at Publisher · View at Google Scholar · View at Scopus
  120. R. Van Winkel, G. Esquivel, G. Kenis et al., “Genome-wide findings in schizophrenia and the role of gene-environment interplay,” CNS Neuroscience and Therapeutics, vol. 16, no. 5, pp. e185–e192, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. L. French, C. Gray, G. Leonard et al., “Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence,” JAMA Psychiatry, vol. 72, no. 10, pp. 1002–1011, 2015. View at Publisher · View at Google Scholar · View at Scopus
  122. D. Goldman, “America's cannabis experiment,” JAMA Psychiatry, vol. 72, no. 10, pp. 969–970, 2015. View at Publisher · View at Google Scholar · View at Scopus
  123. C. M. P. O'Tuathaigh, M. Hryniewiecka, A. Behan et al., “Chronic adolescent exposure to δ-9-tetrahydrocannabinol in COMT mutant mice: impact on psychosis-related and other phenotypes,” Neuropsychopharmacology, vol. 35, no. 11, pp. 2262–2273, 2010. View at Publisher · View at Google Scholar · View at Scopus
  124. M. Schneider and M. Koch, “Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats,” Neuropsychopharmacology, vol. 28, no. 10, pp. 1760–1769, 2003. View at Publisher · View at Google Scholar · View at Scopus
  125. J. Renard, L. G. Rosen, M. Loureiro et al., “Adolescent cannabinoid exposure induces a persistent sub-cortical hyper-dopaminergic state and associated molecular adaptations in the prefrontal cortex,” Cerebral Cortex, 2016. View at Publisher · View at Google Scholar
  126. P. D. Morrison and R. M. Murray, “From real-world events to psychosis: the emerging neuropharmacology of delusions,” Schizophrenia Bulletin, vol. 35, no. 4, pp. 668–674, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. S. Han, B.-Z. Yang, H. R. Kranzler et al., “Linkage analysis followed by association show NRG1 associated with cannabis dependence in African Americans,” Biological Psychiatry, vol. 72, no. 8, pp. 637–644, 2012. View at Publisher · View at Google Scholar · View at Scopus
  128. A. A. Boucher, G. E. Hunt, T. Karl, J. Micheau, I. S. McGregor, and J. C. Arnold, “Heterozygous neuregulin 1 mice display greater baseline and Δ9-tetrahydrocannabinol-induced c-Fos expression,” Neuroscience, vol. 149, no. 4, pp. 861–870, 2007. View at Publisher · View at Google Scholar · View at Scopus
  129. A. A. Boucher, J. C. Arnold, L. Duffy, P. R. Schofield, J. Micheau, and T. Karl, “Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ9-tetrahydrocannabinol,” Psychopharmacology, vol. 192, no. 3, pp. 325–336, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. L. E. Long, R. Chesworth, J. C. Arnold, and T. Karl, “A follow-up study: acute behavioural effects of Δ9-THC in female heterozygous neuregulin 1 transmembrane domain mutant mice,” Psychopharmacology, vol. 211, no. 3, pp. 277–289, 2010. View at Publisher · View at Google Scholar · View at Scopus
  131. A. A. Boucher, G. E. Hunt, J. Micheau et al., “The schizophrenia susceptibility gene neuregulin 1 modulates tolerance to the effects of cannabinoids,” International Journal of Neuropsychopharmacology, vol. 14, no. 5, pp. 631–643, 2011. View at Publisher · View at Google Scholar · View at Scopus
  132. L. E. Long, R. Chesworth, X.-F. Huang, I. S. McGregor, J. C. Arnold, and T. Karl, “Transmembrane domain Nrg1 mutant mice show altered susceptibility to the neurobehavioural actions of repeated THC exposure in adolescence,” International Journal of Neuropsychopharmacology, vol. 16, no. 1, pp. 163–175, 2013. View at Publisher · View at Google Scholar · View at Scopus
  133. J. R. Spencer, K. M. E. Darbyshire, A. A. Boucher et al., “Novel molecular changes induced by Nrg1 hypomorphism and Nrg1-cannabinoid interaction in adolescence: a hippocampal proteomic study in mice,” Frontiers in Cellular Neuroscience, vol. 7, article 15, 2013. View at Publisher · View at Google Scholar · View at Scopus
  134. J. A. S. Crippa, G. N. Derenusson, T. B. Ferrari et al., “Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report,” Journal of Psychopharmacology, vol. 25, no. 1, pp. 121–130, 2011. View at Publisher · View at Google Scholar · View at Scopus
  135. F. M. Leweke, J. K. Mueller, B. Lange et al., “Therapeutic potential of cannabinoids in psychosis,” Biological Psychiatry, vol. 79, no. 7, pp. 604–612, 2015. View at Publisher · View at Google Scholar
  136. L. E. Long, R. Chesworth, X.-F. Huang et al., “Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice,” PLoS ONE, vol. 7, no. 4, Article ID e34129, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. M. D. Ballinger, A. Saito, B. Abazyan et al., “Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory,” Neurobiology of Disease, vol. 82, pp. 176–184, 2015. View at Publisher · View at Google Scholar · View at Scopus
  138. E. M. Tunbridge, D. R. Weinberger, and P. J. Harrison, “A novel protein isoform of catechol O-methyltransferase (COMT): brain expression analysis in schizophrenia and bipolar disorder and effect of Val158Met genotype,” Molecular Psychiatry, vol. 11, no. 2, pp. 116–117, 2006. View at Publisher · View at Google Scholar · View at Scopus
  139. D. Collip, R. Van Winkel, O. Peerbooms et al., “COMT Val158Met-stress interaction in psychosis: role of background psychosis risk,” CNS Neuroscience and Therapeutics, vol. 17, no. 6, pp. 612–619, 2011. View at Publisher · View at Google Scholar · View at Scopus
  140. X. Goldberg, M. Fatjó-Vilas, S. Alemany, I. Nenadic, C. Gastó, and L. Fañanás, “Gene-environment interaction on cognition: a twin study of childhood maltreatment and COMT variability,” Journal of Psychiatric Research, vol. 47, no. 7, pp. 989–994, 2013. View at Publisher · View at Google Scholar · View at Scopus
  141. S. Alemany, B. Arias, M. Fatjó-Vilas et al., “Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes,” Acta Psychiatrica Scandinavica, vol. 129, no. 1, pp. 54–62, 2014. View at Publisher · View at Google Scholar · View at Scopus
  142. A. Caspi, T. E. Moffitt, M. Cannon et al., “Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction,” Biological Psychiatry, vol. 57, no. 10, pp. 1117–1127, 2005. View at Publisher · View at Google Scholar · View at Scopus
  143. C. M. P. O'Tuathaigh, G. Clarke, J. Walsh et al., “Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes,” International Journal of Neuropsychopharmacology, vol. 15, no. 9, pp. 1331–1342, 2012. View at Publisher · View at Google Scholar · View at Scopus
  144. Á. T. Behan, M. Hryniewiecka, C. M. P. O'Tuathaigh et al., “Chronic adolescent exposure to delta-9-tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways,” Neuropsychopharmacology, vol. 37, no. 7, pp. 1773–1783, 2012. View at Publisher · View at Google Scholar · View at Scopus
  145. L. J. Phillips, P. D. McGorry, B. Garner et al., “Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications for the development of psychotic disorders,” Australian and New Zealand Journal of Psychiatry, vol. 40, no. 9, pp. 725–741, 2006. View at Publisher · View at Google Scholar · View at Scopus
  146. K. D. Tessner, V. Mittal, and E. F. Walker, “Longitudinal study of stressful life events and daily stressors among adolescents at high risk for psychotic disorders,” Schizophrenia Bulletin, vol. 37, no. 2, pp. 432–441, 2011. View at Publisher · View at Google Scholar · View at Scopus
  147. F. Varese, E. Barkus, and R. P. Bentall, “Dissociation mediates the relationship between childhood trauma and hallucination-proneness,” Psychological Medicine, vol. 42, no. 5, pp. 1025–1036, 2012. View at Publisher · View at Google Scholar · View at Scopus
  148. J.-P. Selten and E. Cantor-Graae, “Hypothesis: social defeat is a risk factor for schizophrenia?” The British Journal of Psychiatry, vol. 191, no. 51, pp. s9–s12, 2007. View at Publisher · View at Google Scholar
  149. J.-P. Selten, E. van der Ven, B. P. F. Rutten, and E. Cantor-Graae, “The social defeat hypothesis of schizophrenia: an update,” Schizophrenia Bulletin, vol. 39, no. 6, pp. 1180–1186, 2013. View at Publisher · View at Google Scholar · View at Scopus
  150. C. Hammels, E. Pishva, J. De Vry et al., “Defeat stress in rodents: from behavior to molecules,” Neuroscience and Biobehavioral Reviews, vol. 59, pp. 111–140, 2015. View at Publisher · View at Google Scholar · View at Scopus
  151. O. Berton, C. A. McClung, R. J. DiLeone et al., “Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress,” Science, vol. 311, no. 5762, pp. 864–868, 2006. View at Publisher · View at Google Scholar · View at Scopus
  152. V. Krishnan, M. Han, D. L. Graham et al., “Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions,” Cell, vol. 131, no. 2, pp. 391–404, 2007. View at Publisher · View at Google Scholar
  153. T. W. Chohan, A. A. Boucher, J. R. Spencer et al., “Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice,” Schizophrenia Bulletin, vol. 40, no. 6, pp. 1272–1284, 2014. View at Publisher · View at Google Scholar · View at Scopus
  154. F. N. Haque, T. V. Lipina, J. C. Roder, and A. H. C. Wong, “Social defeat interacts with Disc1 mutations in the mouse to affect behavior,” Behavioural Brain Research, vol. 233, no. 2, pp. 337–344, 2012. View at Publisher · View at Google Scholar · View at Scopus
  155. M. Niwa, H. Jaaro-Peled, S. Tankou et al., “Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids,” Science, vol. 339, no. 6117, pp. 335–339, 2013. View at Publisher · View at Google Scholar · View at Scopus
  156. R. E. Straub, Y. Jiang, C. J. MacLean et al., “Genetic variation in the 6p22.3 Gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia,” American Journal of Human Genetics, vol. 71, no. 2, pp. 337–348, 2002. View at Publisher · View at Google Scholar · View at Scopus
  157. B. Riley, P.-H. Kuo, B. S. Maher et al., “The dystrobrevin binding protein 1 (DTNBP1) gene is associated with schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS) sample,” Schizophrenia Research, vol. 115, no. 2-3, pp. 245–253, 2009. View at Publisher · View at Google Scholar · View at Scopus
  158. M. Ayalew, H. Le-Niculescu, D. F. Levey et al., “Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction,” Molecular Psychiatry, vol. 17, no. 9, pp. 887–905, 2012. View at Publisher · View at Google Scholar · View at Scopus
  159. K. E. Burdick, T. E. Goldberg, B. Funke et al., “DTNBP1 genotype influences cognitive decline in schizophrenia,” Schizophrenia Research, vol. 89, no. 1–3, pp. 169–172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  160. A. J. Fallgatter, A.-C. Ehlis, M. J. Herrmann et al., “DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in schizophrenic patients—support for the glutamate hypothesis of schizophrenias,” Genes, Brain and Behavior, vol. 9, no. 5, pp. 489–497, 2010. View at Publisher · View at Google Scholar · View at Scopus
  161. J.-P. Zhang, K. E. Burdick, T. Lencz, and A. K. Malhotra, “Meta-analysis of genetic variation in DTNBP1 and general cognitive ability,” Biological Psychiatry, vol. 68, no. 12, pp. 1126–1133, 2010. View at Publisher · View at Google Scholar · View at Scopus
  162. C. S. Weickert, D. A. Rothmond, T. M. Hyde, J. E. Kleinman, and R. E. Straub, “Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients,” Schizophrenia Research, vol. 98, no. 1–3, pp. 105–110, 2008. View at Publisher · View at Google Scholar · View at Scopus
  163. J. Tang, R. P. LeGros, N. Louneva et al., “Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression,” Human Molecular Genetics, vol. 18, no. 20, pp. 3851–3863, 2009. View at Publisher · View at Google Scholar · View at Scopus
  164. C. Fu, D. Chen, R. Chen, Q. Hu, G. Wang, and K.-L. Lim, “The schizophrenia-related protein dysbindin-1A is degraded and facilitates NF-Kappa B activity in the nucleus,” PLoS ONE, vol. 10, no. 7, Article ID e0132639, 2015. View at Publisher · View at Google Scholar · View at Scopus
  165. R. T. Swank, H. O. Sweet, M. T. Davisson, M. Reddington, and E. K. Novak, “Sandy: a new mouse model for platelet storage pool deficiency,” Genetical Research, vol. 58, no. 1, pp. 51–62, 1991. View at Publisher · View at Google Scholar · View at Scopus
  166. K. Takao, K. Toyama, K. Nakanishi et al., “Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia,” Molecular brain, vol. 1, article 11, 2008. View at Publisher · View at Google Scholar · View at Scopus
  167. J. D. Jentsch, H. Trantham-Davidson, C. Jairl, M. Tinsley, T. D. Cannon, and A. Lavin, “Dysbindin modulates prefrontal cortical glutamatergic circuits and working memory function in mice,” Neuropsychopharmacology, vol. 34, no. 12, pp. 2601–2608, 2009. View at Publisher · View at Google Scholar · View at Scopus
  168. K. H. Karlsgodt, K. Robleto, H. Trantham-Davidson et al., “Reduced dysbindin expression mediates N-methyl-D-aspartate receptor hypofunction and impaired working memory performance,” Biological Psychiatry, vol. 69, no. 1, pp. 28–34, 2011. View at Publisher · View at Google Scholar · View at Scopus
  169. F. Papaleo, F. Yang, S. Garcia et al., “Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways,” Molecular Psychiatry, vol. 17, no. 1, pp. 85–98, 2012. View at Publisher · View at Google Scholar · View at Scopus
  170. W. B. Glen Jr., B. Horowitz, G. C. Carlson et al., “Dysbindin-1 loss compromises NMDAR-dependent synaptic plasticity and contextual fear conditioning,” Hippocampus, vol. 24, no. 2, pp. 204–213, 2014. View at Publisher · View at Google Scholar · View at Scopus
  171. S. K. Bhardwaj, R. T. Ryan, T. P. Wong, and L. K. Srivastava, “Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1 metabotropic glutamate receptor function in mice,” Frontiers in Behavioral Neuroscience, vol. 9, article 72, 2015. View at Publisher · View at Google Scholar · View at Scopus
  172. F. Papaleo and D. R. Weinberger, “Dysbindin and Schizophrenia: it's dopamine and glutamate all over again,” Biological Psychiatry, vol. 69, no. 1, pp. 2–4, 2011. View at Publisher · View at Google Scholar · View at Scopus
  173. M. M. Cox, A. M. Tucker, J. Tang et al., “Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background,” Genes, Brain and Behavior, vol. 8, no. 4, pp. 390–397, 2009. View at Publisher · View at Google Scholar · View at Scopus
  174. K. K. Nicodemus, S. Marenco, A. J. Batten et al., “Serious obstetric complications interact with hypoxia-regulated/vascular- expression genes to influence schizophrenia risk,” Molecular Psychiatry, vol. 13, no. 9, pp. 873–877, 2008. View at Publisher · View at Google Scholar · View at Scopus
  175. J. Voisey, C. D. Swagell, I. P. Hughes et al., “A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia,” Behavioral and Brain Functions, vol. 6, article 41, 2010. View at Publisher · View at Google Scholar · View at Scopus
  176. S. Hattori, T. Murotani, S. Matsuzaki et al., “Behavioral abnormalities and dopamine reductions in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia,” Biochemical and Biophysical Research Communications, vol. 373, no. 2, pp. 298–302, 2008. View at Publisher · View at Google Scholar · View at Scopus
  177. C. A. Ghiani, M. Starcevic, I. A. Rodriguez-Fernandez et al., “The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth,” Molecular Psychiatry, vol. 15, no. 2, pp. 204–215, 2010. View at Publisher · View at Google Scholar · View at Scopus
  178. T. C. Südhof and J. E. Rothman, “Membrane fusion: grappling with SNARE and SM proteins,” Science, vol. 323, no. 5913, pp. 474–477, 2009. View at Publisher · View at Google Scholar · View at Scopus
  179. C. M. Lewis, D. F. Levinson, L. H. Wise et al., “Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia,” American Journal of Human Genetics, vol. 73, no. 1, pp. 34–48, 2003. View at Publisher · View at Google Scholar
  180. J. Lochman, V. J. Balcar, F. Šťastný, and O. Šerý, “Preliminary evidence for association between schizophrenia and polymorphisms in the regulatory regions of the ADRA2A, DRD3 and SNAP-25 genes,” Psychiatry Research, vol. 205, no. 1-2, pp. 7–12, 2013. View at Publisher · View at Google Scholar · View at Scopus
  181. X. Fan and E. J. Hess, “D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD,” Neurobiology of Disease, vol. 26, no. 1, pp. 201–211, 2007. View at Publisher · View at Google Scholar · View at Scopus
  182. X. Fan, M. Xu, and E. J. Hess, “D2 dopamine receptor subtype-mediated hyperactivity and amphetamine responses in a model of ADHD,” Neurobiology of Disease, vol. 37, no. 1, pp. 228–236, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. P. L. Oliver and K. E. Davies, “Interaction between environmental and genetic factors modulates schizophrenic endophenotypes in the Snap-25 mouse mutant blind-drunk,” Human Molecular Genetics, vol. 18, no. 23, pp. 4576–4589, 2009. View at Publisher · View at Google Scholar · View at Scopus
  184. M. Baca, A. M. Allan, L. D. Partridge, and M. C. Wilson, “Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice,” Brain Research, vol. 1532, pp. 85–98, 2013. View at Publisher · View at Google Scholar · View at Scopus
  185. T. Niitsu, T. Ishima, T. Yoshida et al., “A positive correlation between serum levels of mature brain-derived neurotrophic factor and negative symptoms in schizophrenia,” Psychiatry Research, vol. 215, no. 2, pp. 268–273, 2014. View at Publisher · View at Google Scholar · View at Scopus
  186. C. Theleritis, H. L. Fisher, I. Shäfer et al., “Brain derived neurotropic factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis,” Schizophrenia Research, vol. 159, no. 1, pp. 56–61, 2014. View at Publisher · View at Google Scholar · View at Scopus
  187. E. Dong, P. Tueting, F. Matrisciano, D. R. Grayson, and A. Guidotti, “Behavioral and molecular neuroepigenetic alterations in prenatally stressed mice: relevance for the study of chromatin remodeling properties of antipsychotic drugs,” Translational Psychiatry, vol. 6, article e711, 2016. View at Publisher · View at Google Scholar
  188. E. E. Manning, A. L. Halberstadt, and M. van den Buuse, “BDNF-deficient mice show reduced psychosis-related behaviors following chronic methamphetamine,” International Journal of Neuropsychopharmacology, vol. 19, no. 4, 2016. View at Publisher · View at Google Scholar
  189. E. E. Manning and M. van den Buuse, “BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation,” Frontiers in Cellular Neuroscience, vol. 7, article 92, 2013. View at Publisher · View at Google Scholar · View at Scopus
  190. S. H. Fatemi, J. A. Earle, and T. McMenomy, “Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression,” Molecular Psychiatry, vol. 5, no. 6, pp. 654–663, 2000. View at Publisher · View at Google Scholar · View at Scopus
  191. I. Knuesel, “Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases,” Progress in Neurobiology, vol. 91, no. 4, pp. 257–274, 2010. View at Publisher · View at Google Scholar · View at Scopus
  192. G. Laviola, E. Ognibene, E. Romano, W. Adriani, and F. Keller, “Gene-environment interaction during early development in the heterozygous reeler mouse: clues for modelling of major neurobehavioral syndromes,” Neuroscience and Biobehavioral Reviews, vol. 33, no. 4, pp. 560–572, 2009. View at Publisher · View at Google Scholar · View at Scopus
  193. E. Ognibene, W. Adriani, S. Macrì, and G. Laviola, “Neurobehavioural disorders in the infant reeler mouse model: interaction of genetic vulnerability and consequences of maternal separation,” Behavioural Brain Research, vol. 177, no. 1, pp. 142–149, 2007. View at Publisher · View at Google Scholar · View at Scopus
  194. K. R. Howell and A. Pillai, “Effects of prenatal hypoxia on schizophrenia-related phenotypes in heterozygous reeler mice: a gene × environment interaction study,” European Neuropsychopharmacology, vol. 24, no. 8, pp. 1324–1336, 2014. View at Publisher · View at Google Scholar · View at Scopus
  195. Y. Ayhan, A. Sawa, C. A. Ross, and M. V. Pletnikov, “Animal models of gene-environment interactions in schizophrenia,” Behavioural Brain Research, vol. 204, no. 2, pp. 274–281, 2009. View at Publisher · View at Google Scholar · View at Scopus
  196. E. L. Burrows, C. E. McOmish, and A. J. Hannan, “Gene-environment interactions and construct validity in preclinical models of psychiatric disorders,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 35, no. 6, pp. 1376–1382, 2011. View at Publisher · View at Google Scholar · View at Scopus
  197. I. Myin-Germeys, P. Delespaul, and J. van Os, “Behavioural sensitization to daily life stress in psychosis,” Psychological Medicine, vol. 35, no. 5, pp. 733–741, 2005. View at Publisher · View at Google Scholar · View at Scopus
  198. R. D. Goodwin, X. F. Amador, D. Malaspina, S. A. Yale, R. R. Goetz, and J. M. Gorman, “Anxiety and substance use comorbidity among inpatients with schizophrenia,” Schizophrenia Research, vol. 61, no. 1, pp. 89–95, 2003. View at Publisher · View at Google Scholar · View at Scopus
  199. I. Myin-Germeys, M. Oorschot, D. Collip, J. Lataster, p. delespaul, and J. van Os, “Experience sampling research in psychopathology: opening the black box of daily life,” Psychological Medicine, vol. 39, no. 9, pp. 1533–1547, 2009. View at Publisher · View at Google Scholar · View at Scopus
  200. J. M. Goldstein, L. J. Seidman, J. M. Goodman et al., “Are there sex differences in neuropsychological functions among patients with schizophrenia?” American Journal of Psychiatry, vol. 155, no. 10, pp. 1358–1364, 1998. View at Publisher · View at Google Scholar
  201. M. Han, X.-F. Huang, D. C. Chen et al., “Gender differences in cognitive function of patients with chronic schizophrenia,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 39, no. 2, pp. 358–363, 2012. View at Publisher · View at Google Scholar · View at Scopus
  202. D. A. Lewis, A. A. Curley, J. R. Glausier, and D. W. Volk, “Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia,” Trends in Neurosciences, vol. 35, no. 1, pp. 57–67, 2012. View at Publisher · View at Google Scholar · View at Scopus
  203. S. Canetta, S. Bolkan, N. Padilla-Coreano et al., “Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons,” Molecular Psychiatry, vol. 21, no. 7, pp. 956–968, 2016. View at Publisher · View at Google Scholar
  204. J. van Os and S. Kapur, “Schizophrenia,” The Lancet, vol. 374, no. 9690, pp. 635–645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  205. R. M. Murray, L. Sideli, C. La Cascia, and D. La Barbera, “Bridging the gap between research into biological and psychosocial models of psychosis,” Shanghai Archives of Psychiatry, vol. 27, no. 3, pp. 139–143, 2015. View at Publisher · View at Google Scholar · View at Scopus
  206. O. D. Howes, C. McDonald, M. Cannon, L. Arseneault, J. Boydell, and R. M. Murray, “Pathways to schizophrenia: the impact of environmental factors,” International Journal of Neuropsychopharmacology, vol. 7, no. 1, pp. S7–S13, 2004. View at Publisher · View at Google Scholar · View at Scopus
  207. P. J. Harrison and D. R. Weinberger, “Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence,” Molecular Psychiatry, vol. 10, no. 1, pp. 40–68, 2005. View at Publisher · View at Google Scholar · View at Scopus