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The myelin-pathogenesis puzzle in schizophrenia: a literature review

Molecular Psychiatry volume 13, pages 245–260 (2008)Cite this article

Abstract

Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

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References

  1. Kirov G, O'Donovan MC, Owen MJ . Finding schizophrenia genes. J Clin Invest 2005; 115: 1440–1448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tsuang MT, Stone WS, Faraone SV . Genes, environment and schizophrenia. Br J Psychiatry 2001; 178(Suppl 40): s18–s24.

    Article  Google Scholar 

  3. Harrison PJ, Weinberger DR . Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005; 10: 40–68; image 45.

    Article  CAS  PubMed  Google Scholar 

  4. Sullivan PF, Kendler KS, Neale MC . Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003; 60: 1187–1192.

    Article  PubMed  Google Scholar 

  5. Harrison PJ, Owen MJ . Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 2003; 361: 417–419.

    Article  CAS  PubMed  Google Scholar 

  6. Uranova N, Orlovskaya D, Vikhreva O, Zimina I, Kolomeets N, Vostrikov V et al. Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 2001; 55: 597–610.

    Article  CAS  PubMed  Google Scholar 

  7. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 2001; 98: 4746–4751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sawa A, Snyder SH . Schizophrenia: diverse approaches to a complex disease. Science 2002; 296: 692–695.

    Article  CAS  PubMed  Google Scholar 

  9. Bunney WE, Bunney BG, Vawter MP, Tomita H, Li J, Evans SJ et al. Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders. Am J Psychiatry 2003; 160: 657–666.

    Article  PubMed  Google Scholar 

  10. Riley BP, McGuffin P . Linkage and associated studies of schizophrenia. Am J Med Genet 2000; 97: 23–44.

    Article  CAS  PubMed  Google Scholar 

  11. Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y et al. Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p. Am J Hum Genet 2005; 77: 937–944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gurling HM, Kalsi G, Brynjolfson J, Sigmundsson T, Sherrington R, Mankoo BS et al. Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21–22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3–24 and 20q12.1–11.23. Am J Hum Genet 2001; 68: 661–673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Owen MJ, Craddock N, O'Donovan MC . Schizophrenia: genes at last? Trends Genet 2005; 21: 518–525.

    Article  CAS  PubMed  Google Scholar 

  14. Norton N, Williams HJ, Owen MJ . An update on the genetics of schizophrenia. Curr Opin Psychiatry 2006; 19: 158–164.

    Article  PubMed  Google Scholar 

  15. Hennah W, Thomson P, Peltonen L, Porteous D . Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness. Schizophr Bull 2006; 32: 409–416.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ . 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 2001; 69: 428–433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kirkpatrick B, Xu L, Cascella N, Ozeki Y, Sawa A, Roberts RC . DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex. J Comp Neurol 2006; 497: 436–450.

    Article  PubMed  Google Scholar 

  18. Rizig MA, McQuillin A, Puri V, Choudhury K, Datta S, Thirumalai S et al. Failure to confirm genetic association between schizophrenia and markers on chromosome 1q23.3 in the region of the gene encoding the regulator of G-protein signaling 4 protein (RGS4). Am J Med Genet B Neuropsychiatr Genet 2006; 141: 296–300.

    Article  CAS  Google Scholar 

  19. Thaker GK, Carpenter Jr WT . Advances in schizophrenia. Nat Med 2001; 7: 667–671.

    Article  CAS  PubMed  Google Scholar 

  20. Mah S, Nelson MR, Delisi LE, Reneland RH, Markward N, James MR et al. Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. Mol Psychiatry 2006; 11: 471–478.

    Article  CAS  PubMed  Google Scholar 

  21. Zheng Y, Li H, Qin W, Chen W, Duan Y, Xiao Y et al. Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population. Biochem Biophys Res Commun 2005; 328: 809–815.

    Article  CAS  PubMed  Google Scholar 

  22. Puri V, McQuillin A, Thirumalai S, Lawrence J, Krasucki R, Choudhury K et al. Failure to confirm allelic association between markers at the CAPON gene locus and schizophrenia in a British sample. Biol Psychiatry 2006; 59: 195–197.

    Article  CAS  PubMed  Google Scholar 

  23. Wijsman EM, Rosenthal EA, Hall D, Blundell ML, Sobin C, Heath SC et al. Genome-wide scan in a large complex pedigree with predominantly male schizophrenics from the island of Kosrae: evidence for linkage to chromosome 2q. Mol Psychiatry 2003; 8: 695–705, 643.

    Article  CAS  PubMed  Google Scholar 

  24. Maziade M, Debraekeleer M, Genest P, Cliche D, Fournier JP, Garneau Y et al. A balanced 2:18 translocation and familial schizophrenia: falling short of an association. Arch Gen Psychiatry 1993; 50: 73–75.

    CAS  PubMed  Google Scholar 

  25. Addington AM, Gornick M, Duckworth J, Sporn A, Gogtay N, Bobb A et al. GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry 2005; 10: 581–588.

    Article  CAS  PubMed  Google Scholar 

  26. Bellivier F . Schizophrenia, antipsychotics and diabetes: genetic aspects. Eur Psychiatry 2005; 20(Suppl 4): S335–339.

    Article  PubMed  Google Scholar 

  27. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN . Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003; 33: 177–182.

    Article  CAS  PubMed  Google Scholar 

  28. Schosser A, Fuchs K, Leisch F, Bailer U, Meszaros K, Lenzinger E et al. Possible linkage of schizophrenia and bipolar affective disorder to chromosome 3q29; a follow-up. J Psychiatr Res 2004; 38: 357–364.

    Article  PubMed  Google Scholar 

  29. Klei L, Bacanu SA, Myles-Worsley M, Galke B, Xie W, Tiobech J et al. Linkage analysis of a completely ascertained sample of familial schizophrenics and bipolars from Palau, Micronesia. Hum Genet 2005; 117: 349–356.

    Article  CAS  PubMed  Google Scholar 

  30. Bulayeva KB, Leal SM, Pavlova TA, Kurbanov RM, Glatt SJ, Bulayev OA et al. Mapping genes of complex psychiatric diseases in Daghestan genetic isolates. Am J Med Genet B Neuropsychiatr Genet 2005; 132: 76–84.

    Article  Google Scholar 

  31. Chen QY, Chen Q, Feng GY, Lindpaintner K, Chen Y, Sun X et al. Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population. Schizophr Res 2005; 73: 269–274.

    Article  PubMed  Google Scholar 

  32. Muir WJ, Thomson ML, McKeon P, Mynett-Johnson L, Whitton C, Evans KL et al. Markers close to the dopamine D5 receptor gene (DRD5) show significant association with schizophrenia but not bipolar disorder. Am J Med Genet 2001; 105: 152–158.

    Article  CAS  PubMed  Google Scholar 

  33. Underwood SL, Christoforou A, Thomson PA, Wray NR, Tenesa A, Whittaker J et al. Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia. Mol Psychiatry 2006; 11: 384–394.

    Article  CAS  PubMed  Google Scholar 

  34. Itokawa M, Kasuga T, Yoshikawa T, Matsushita M . Identification of a male schizophrenic patient carrying a de novo balanced translocation, t(4; 13)(p16.1; q21.31). Psychiatry Clin Neurosci 2004; 58: 333–337.

    Article  PubMed  Google Scholar 

  35. Cooper-Casey K, Mesen-Fainardi A, Galke-Rollins B, Llach M, Laprade B, Rodriguez C et al. Suggestive linkage of schizophrenia to 5p13 in Costa Rica. Mol Psychiatry 2005; 10: 651–656.

    Article  CAS  PubMed  Google Scholar 

  36. Berry N, Jobanputra V, Pal H . Molecular genetics of schizophrenia: a critical review. J Psychiatry Neurosci 2003; 28: 415–429.

    PubMed  PubMed Central  Google Scholar 

  37. Pimm J, McQuillin A, Thirumalai S, Lawrence J, Quested D, Bass N et al. The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia. Am J Hum Genet 2005; 76: 902–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wasiak S, Legendre-Guillemin V, Puertollano R, Blondeau F, Girard M, de Heuvel E et al. Enthoprotin: a novel clathrin-associated protein identified through subcellular proteomics. J Cell Biol 2002; 158: 855–862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cui DH, Jiang KD, Jiang SD, Xu YF, Yao H . The tumor suppressor adenomatous polyposis coli gene is associated with susceptibility to schizophrenia. Mol Psychiatry 2005; 10: 669–677.

    Article  CAS  PubMed  Google Scholar 

  40. Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell S, Aldinger KA et al. Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. Mol Psychiatry 2005; 10: 1074–1088, 1057.

    Article  CAS  PubMed  Google Scholar 

  41. Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y et al. Association analysis of chromosome 5 GABAA receptor cluster in Japanese schizophrenia patients. Biol Psychiatry 2005; 58: 440–445.

    Article  CAS  PubMed  Google Scholar 

  42. Seal JL, Gornick MC, Gogtay N, Shaw P, Greenstein DK, Coffey M et al. Segmental uniparental isodisomy on 5q32-qter in a patient with childhood-onset schizophrenia. J Med Genet 2006; 43: 887–892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lerer B, Segman RH, Hamdan A, Kanyas K, Karni O, Kohn Y et al. Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24. Mol Psychiatry 2003; 8: 488–498.

    Article  CAS  PubMed  Google Scholar 

  44. Arolt V, Lencer R, Nolte A, Muller-Myhsok B, Purmann S, Schurmann M et al. Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. Am J Med Genet 1996; 67: 564–579.

    Article  CAS  PubMed  Google Scholar 

  45. Riley B, Kendler KS . Molecular genetic studies of schizophrenia. Eur J Hum Genet 2006; 14: 669–680.

    Article  CAS  PubMed  Google Scholar 

  46. Grady RM, Zhou H, Cunningham JM, Henry MD, Campbell KP, Sanes JR . Maturation and maintenance of the neuromuscular synapse: genetic evidence for roles of the dystrophin—glycoprotein complex. Neuron 2000; 25: 279–293.

    Article  CAS  PubMed  Google Scholar 

  47. Duan J, Martinez M, Sanders AR, Hou C, Saitou N, Kitano T et al. Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia. Am J Hum Genet 2004; 75: 624–638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kohn Y, Lerer B . Excitement and confusion on chromosome 6q: the challenges of neuropsychiatric genetics in microcosm. Mol Psychiatry 2005; 10: 1062–1073.

    Article  CAS  PubMed  Google Scholar 

  49. Abdolmaleky HM, Cheng KH, Russo A, Smith CL, Faraone SV, Wilcox M et al. Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. Am J Med Genet B Neuropsychiatr Genet 2005; 134: 60–66.

    Article  Google Scholar 

  50. Fatemi SH . Reelin glycoprotein: structure, biology and roles in health and disease. Mol Psychiatry 2005; 10: 251–257.

    Article  CAS  PubMed  Google Scholar 

  51. Goldberger C, Gourion D, Leroy S, Schurhoff F, Bourdel MC, Leboyer M et al. Population-based and family-based association study of 5'UTR polymorphism of the reelin gene and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2005; 137: 51–55.

    Article  Google Scholar 

  52. Marenco S, Steele SU, Egan MF, Goldberg TE, Straub RE, Sharrief AZ et al. Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate measures in the dorsolateral prefrontal cortex. Am J Psychiatry 2006; 163: 740–742.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Walss-Bass C, Montero AP, Armas R, Dassori A, Contreras SA, Liu W et al. Linkage disequilibrium analyses in the Costa Rican population suggests discrete gene loci for schizophrenia at 8p23*1 and 8q13*3. Psychiatr Genet 2006; 16: 159–168.

    Article  PubMed  Google Scholar 

  54. Duan J, Martinez M, Sanders AR, Hou C, Krasner AJ, Schwartz DB et al. Neuregulin 1 (NRG1) and schizophrenia: analysis of a US family sample and the evidence in the balance. Psychol Med 2005; 35: 1599–1610.

    Article  PubMed  Google Scholar 

  55. Miyamoto S, LaMantia AS, Duncan GE, Sullivan P, Gilmore JH, Lieberman JA . Recent advances in the neurobiology of schizophrenia. Mol Interv 2003; 3: 27–39.

    Article  PubMed  Google Scholar 

  56. Tosato S, Dazzan P, Collier D . Association between the neuregulin 1 gene and schizophrenia: a systematic review. Schizophr Bull 2005; 31: 613–617.

    Article  PubMed  Google Scholar 

  57. Vartanian T, Corfas G, Li Y, Fischbach GD, Stefansson K . A role for the acetylcholine receptor-inducing protein ARIA in oligodendrocyte development. Proc Natl Acad Sci USA 1994; 91: 11626–11630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Liu CM, Hwu HG, Fann CS, Lin CY, Liu YL, Ou-Yang WC et al. Linkage evidence of schizophrenia to loci near neuregulin 1 gene on chromosome 8p21 in Taiwanese families. Am J Med Genet B Neuropsychiatr Genet 2005; 134: 79–83.

    Article  Google Scholar 

  59. Nanko S, Kunugi H, Sasaki T, Fukuda R, Kawate T, Kazamatsuri H . Pericentric region of chromosome 9 is a possible candidate region for linkage study of schizophrenia. Biol Psychiatry 1993; 33: 655–658.

    Article  CAS  PubMed  Google Scholar 

  60. Demirhan O, Tastemir D . Chromosome aberrations in a schizophrenia population. Schizophr Res 2003; 65: 1–7.

    Article  PubMed  Google Scholar 

  61. Pickard BS, Malloy MP, Porteous DJ, Blackwood DH, Muir WJ . Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability. Am J Med Genet B Neuropsychiatr Genet 2005; 136: 26–32.

    Article  Google Scholar 

  62. Freedman R, Leonard S, Olincy A, Kaufmann CA, Malaspina D, Cloninger CR et al. Evidence for the multigenic inheritance of schizophrenia. Am J Med Genet 2001; 105: 794–800.

    Article  CAS  PubMed  Google Scholar 

  63. Fallin MD, Lasseter VK, Wolyniec PS, McGrath JA, Nestadt G, Valle D et al. Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22. Am J Hum Genet 2003; 73: 601–611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Perlman WR, Weickert CS, Akil M, Kleinman JE . Postmortem investigations of the pathophysiology of schizophrenia: the role of susceptibility genes. J Psychiatry Neurosci 2004; 29: 287–293.

    PubMed  PubMed Central  Google Scholar 

  65. Wassink TH, Nelson JJ, Crowe RR, Andreasen NC . Heritability of BDNF alleles and their effect on brain morphology in schizophrenia. Am J Med Genet 1999; 88: 724–728.

    Article  CAS  PubMed  Google Scholar 

  66. Egan MF, Weinberger DR, Lu B . Schizophrenia, III: brain-derived neurotropic factor and genetic risk. Am J Psychiatry 2003; 160: 1242.

    Article  PubMed  Google Scholar 

  67. Hashimoto T, Bergen SE, Nguyen QL, Xu B, Monteggia LM, Pierri JN et al. Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci 2005; 25: 372–383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Yamada K, Iwayama-Shigeno Y, Yoshida Y, Toyota T, Itokawa M, Hattori E et al. Family-based association study of schizophrenia with 444 markers and analysis of a new susceptibility locus mapped to 11q13.3. Am J Med Genet B Neuropsychiatr Genet 2004; 127: 11–19.

    Article  Google Scholar 

  69. Ma J, Qin W, Wang XY, Guo TW, Bian L, Duan SW et al. Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations. Mol Psychiatry 2006; 11: 479–487.

    Article  CAS  PubMed  Google Scholar 

  70. Zhang H, Ju G, Wei J, Hu Y, Liu L, Xu Q et al. A combined effect of the KPNA3 and KPNB3 genes on susceptibility to schizophrenia. Neurosci Lett 2006; 402: 173–175.

    Article  CAS  PubMed  Google Scholar 

  71. Li D, Duan Y, He L . Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis. Biochem Biophys Res Commun 2006; 340: 1006–1015.

    Article  CAS  PubMed  Google Scholar 

  72. Kamnasaran D, Muir WJ, Ferguson-Smith MA, Cox DW . Disruption of the neuronal PAS3 gene in a family affected with schizophrenia. J Med Genet 2003; 40: 325–332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997; 94: 587–592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Martin LF, Kem WR, Freedman R . Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia. Psychopharmacology (Berl) 2004; 174: 54–64.

    Article  CAS  Google Scholar 

  75. De Luca V, Wang H, Squassina A, Wong GW, Yeomans J, Kennedy JL . Linkage of M5 muscarinic and alpha7-nicotinic receptor genes on 15q13 to schizophrenia. Neuropsychobiology 2004; 50: 124–127.

    Article  CAS  PubMed  Google Scholar 

  76. Walss-Bass C, Escamilla MA, Raventos H, Montero AP, Armas R, Dassori A et al. Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population. Am J Med Genet B Neuropsychiatr Genet 2005; 139: 54–60.

    Article  CAS  Google Scholar 

  77. Faraone SV, Skol AD, Tsuang DW, Young KA, Haverstock SL, Prabhudesai S et al. Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14. Am J Med Genet B Neuropsychiatr Genet 2005; 139: 91–100.

    Article  Google Scholar 

  78. Corradi JP, Ravyn V, Robbins AK, Hagan KW, Peters MF, Bostwick R et al. Alternative transcripts and evidence of imprinting of GNAL on 18p11.2. Mol Psychiatry 2005; 10: 1017–1025.

    Article  CAS  PubMed  Google Scholar 

  79. Washizuka S, Kametani M, Sasaki T, Tochigi M, Umekage T, Kohda K et al. Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population. Am J Med Genet B Neuropsychiatr Genet 2006; 141: 301–304.

    Article  CAS  Google Scholar 

  80. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL et al. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 2004; 9: 684–697, 643.

    Article  CAS  PubMed  Google Scholar 

  81. Iwamoto K, Bundo M, Kato T . Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet 2005; 14: 241–253.

    Article  CAS  PubMed  Google Scholar 

  82. Murphy KC, Jones LA, Owen MJ . High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry 1999; 56: 940–945.

    Article  CAS  PubMed  Google Scholar 

  83. Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS, Lipska BK et al. Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 2001; 50: 825–844.

    Article  CAS  PubMed  Google Scholar 

  84. Liu H, Heath SC, Sobin C, Roos JL, Galke BL, Blundell ML et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci USA 2002; 99: 3717–3722.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Williams HJ, Williams N, Spurlock G, Norton N, Zammit S, Kirov G et al. Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2003; 120: 42–46.

    Article  Google Scholar 

  86. Leung A, Chue P . Sex differences in schizophrenia, a review of the literature. Acta Psychiatrica Scandinavica 2000; 101: 3–38.

    Article  Google Scholar 

  87. Crow TJ . Is schizophrenia the price that Homo sapiens pays for language? Schizophr Res 1997; 28: 127–141.

    Article  CAS  PubMed  Google Scholar 

  88. DeLisi LE, Sakuma M, Kushner M, Finer DL, Hoff AL, Crow TJ . Anomalous cerebral asymmetry and language processing in schizophrenia. Schizophr Bull 1997; 23: 255–271.

    Article  CAS  PubMed  Google Scholar 

  89. Crow TJ . Schizophrenia as the price that Homo sapiens pays for language: a resolution of the central paradox in the origin of the species. Brain Res Brain Res Rev 2000; 31: 118–129.

    Article  CAS  PubMed  Google Scholar 

  90. Nicholson TR, Yang J, DeLisi LE, Crow TJ . Allele sharing for schizophrenia and schizo-affective disorder within a region of Homo sapiens specific XY homology. Am J Med Genet 2002; 114: 637–640.

    Article  PubMed  Google Scholar 

  91. Giouzeli M, Williams NA, Lonie LJ, DeLisi LE, Crow TJ . ProtocadherinX/Y, a candidate gene-pair for schizophrenia and schizoaffective disorder: a DHPLC investigation of genomic sequence. Am J Med Genet B Neuropsychiatr Genet 2004; 129: 1–9.

    Article  Google Scholar 

  92. Stefansson H, Steinthorsdottir V, Thorgeirsson TE, Gulcher JR, Stefansson K . Neuregulin 1 and schizophrenia. Ann Med 2004; 36: 62–71.

    Article  CAS  PubMed  Google Scholar 

  93. Callicott JH, Straub RE, Pezawas L, Egan MF, Mattay VS, Hariri AR et al. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci USA 2005; 102: 8627–8632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Glatt SJ, Faraone SV, Tsuang MT . Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatry 2003; 160: 469–476.

    Article  PubMed  Google Scholar 

  95. Maier W, Zobel A, Rietschel M . Genetics of schizophrenia and affective disorders. Pharmacopsychiatry 2003; 36(Suppl 3): S195–202.

    CAS  PubMed  Google Scholar 

  96. Badner JA, Gershon ES . Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002; 7: 405–411.

    Article  CAS  PubMed  Google Scholar 

  97. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet 2003; 73: 34–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Williams NM, Norton N, Williams H, Ekholm B, Hamshere ML, Lindblom Y et al. A systematic genomewide linkage study in 353 sib pairs with schizophrenia. Am J Hum Genet 2003; 73: 1355–1367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Deb-Rinker P, O'Reilly RL, Torrey EF, Singh SM . Molecular characterization of a 2.7-kb, 12q13-specific, retroviral-related sequence isolated by RDA from monozygotic twin pairs discordant for schizophrenia. Genome 2002; 45: 381–390.

    Article  CAS  PubMed  Google Scholar 

  100. Frith C . Neuropsychology of schizophrenia, what are the implications of intellectual and experiential abnormalities for the neurobiology of schizophrenia? Br Med Bull 1996; 52: 618–626.

    Article  CAS  PubMed  Google Scholar 

  101. Davis KL, Stewart DG, Friedman JI, Buchsbaum M, Harvey PD, Hof PR et al. White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry 2003; 60: 443–456.

    Article  PubMed  Google Scholar 

  102. Aston C, Jiang L, Sokolov BP . Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res 2004; 77: 858–866.

    Article  CAS  PubMed  Google Scholar 

  103. Bunney WE, Bunney BG . Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia. Brain Res Brain Res Rev 2000; 31: 138–146.

    Article  CAS  PubMed  Google Scholar 

  104. Steiner H, Blum M, Kitai ST, Fedi P . Differential expression of ErbB3 and ErbB4 neuregulin receptors in dopamine neurons and forebrain areas of the adult rat. Exp Neurol 1999; 159: 494–503.

    Article  CAS  PubMed  Google Scholar 

  105. Yau HJ, Wang HF, Lai C, Liu FC . Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: preferential expression by interneurons tangentially migrating from the ganglionic eminences. Cereb Cortex 2003; 13: 252–264.

    Article  PubMed  Google Scholar 

  106. Okada M, Corfas G . Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse. Hippocampus 2004; 14: 337–344.

    Article  CAS  PubMed  Google Scholar 

  107. Esper RM, Pankonin MS, Loeb JA . Neuregulins: versatile growth and differentiation factors in nervous system development and human disease. Brain Res Rev 2006; 51: 161–175.

    Article  CAS  PubMed  Google Scholar 

  108. Bozzali M, Wrabetz L . Axonal signals and oligodendrocyte differentiation. Neurochem Res 2004; 29: 979–988.

    Article  CAS  PubMed  Google Scholar 

  109. Vartanian T, Fischbach G, Miller R . Failure of spinal cord oligodendrocyte development in mice lacking neuregulin. Proc Natl Acad Sci USA 1999; 96: 731–735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Corfas G, Roy K, Buxbaum JD . Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat Neurosci 2004; 7: 575–580.

    Article  CAS  PubMed  Google Scholar 

  111. Stewart DG, Davis KL . Possible contributions of myelin and oligodendrocyte dysfunction to schizophrenia. Int Rev Neurobiol 2004; 59: 381–424.

    Article  CAS  PubMed  Google Scholar 

  112. Li S, Liu BP, Budel S, Li M, Ji B, Walus L et al. lockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury. J Neurosci 2004; 24: 10511–10520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Flynn SW, Lang DJ, Mackay AL, Goghari V, Vavasour IM, Whittall KP et al. Abnormalities of myelination in schizophrenia detected in vivo with MRI, and post-mortem with analysis of oligodendrocyte proteins. Mol Psychiatry 2003; 8: 811–820.

    Article  CAS  PubMed  Google Scholar 

  114. Hao Y, Liu Z, Jiang T, Gong G, Liu H, Tan L et al. White matter integrity of the whole brain is disrupted in first-episode schizophrenia. Neuroreport 2006; 17: 23–26.

    Article  PubMed  Google Scholar 

  115. Schaeren-Wiemers N, Bonnet A, Erb M, Erne B, Bartsch U, Kern F et al. The raft-associated protein MAL is required for maintenance of proper axon—glia interactions in the central nervous system. J Cell Biol 2004; 166: 731–742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Minami T, Nobuhara K, Okugawa G, Takase K, Yoshida T, Sawada S et al. Diffusion tensor magnetic resonance imaging of disruption of regional white matter in schizophrenia. Neuropsychobiology 2003; 47: 141–145.

    Article  CAS  PubMed  Google Scholar 

  117. Peirce TR, Bray NJ, Williams NM, Norton N, Moskvina V, Preece A et al. Convergent evidence for 2′,3′-cyclic nucleotide 3′-phosphodiesterase as a possible susceptibility gene for schizophrenia. Arch Gen Psychiatry 2006; 63: 18–24.

    Article  CAS  PubMed  Google Scholar 

  118. Tkachev D, Mimmack ML, Ryan MM, Wayland M, Freeman T, Jones PB et al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 2003; 362: 798–805.

    Article  CAS  PubMed  Google Scholar 

  119. Yang YF, Qin W, Shugart YY, He G, Liu XM, Zhou J et al. Possible association of the MAG locus with schizophrenia in a Chinese Han cohort of family trios. Schizophr Res 2005; 75: 11–19.

    Article  CAS  PubMed  Google Scholar 

  120. Wan C, Yang Y, Feng G, Gu N, Liu H, Zhu S et al. Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population. Neurosci Lett 2005; 388: 126–131.

    Article  CAS  PubMed  Google Scholar 

  121. Sugai T, Kawamura M, Iritani S, Araki K, Makifuchi T, Imai C et al. Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression. Ann NY Acad Sci 2004; 1025: 84–91.

    Article  CAS  PubMed  Google Scholar 

  122. Galiano MR, Andrieux A, Deloulme JC, Bosc C, Schweitzer A, Job D et al. Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes. J Neurosci Res 2006; 84: 534–541.

    Article  CAS  PubMed  Google Scholar 

  123. Chambers JS, Perrone-Bizzozero NI . Altered myelination of the hippocampal formation in subjects with schizophrenia and bipolar disorder. Neurochem Res 2004; 29: 2293–2302.

    Article  CAS  PubMed  Google Scholar 

  124. Comings DE, Pekkula-Flagan A . Two-dimensional gel electrophoresis of human brain proteins. V. Non-equilibrium gel electrophoresis, with detection of a myelin basic protein mutation—MBL-Duarte. Clin Chem 1982; 28(4 Part 2): 813–818.

    CAS  PubMed  Google Scholar 

  125. Qin W, Gao J, Xing Q, Yang J, Qian X, Li X et al. A family-based association study of PLP1 and schizophrenia. Neurosci Lett 2005; 375: 207–210.

    Article  CAS  PubMed  Google Scholar 

  126. Liu X, Qin W, He G, Yang Y, Chen Q, Zhou J et al. A family-based association study of the MOG gene with schizophrenia in the Chinese population. Schizophr Res 2005; 73: 275–280.

    Article  PubMed  Google Scholar 

  127. Zai G, King N, Wigg K, Couto J, Wong GW, Honer WG et al. Genetic study of the myelin oligodendrocyte glycoprotein (MOG) gene in schizophrenia. Genes Brain Behav 2005; 4: 2–9.

    Article  CAS  PubMed  Google Scholar 

  128. Pongrac J, Middleton FA, Lewis DA, Levitt P, Mirnics K . Gene expression profiling with DNA microarrays: advancing our understanding of psychiatric disorders. Neurochem Res 2002; 27: 1049–1063.

    Article  CAS  PubMed  Google Scholar 

  129. Aberg K, Saetre P, Jareborg N, Jazin E . Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia. Proc Natl Acad Sci USA 2006; 103: 7482–7487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dracheva S, Davis KL, Chin B, Woo DA, Schmeidler J, Haroutunian V . Myelin-associated mRNA and protein expression deficits in the anterior cingulate cortex and hippocampus in elderly schizophrenia patients. Neurobiol Dis 2006; 21: 531–540.

    Article  CAS  PubMed  Google Scholar 

  131. Davis KL, Haroutunian V . Global expression-profiling studies and oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 2003; 362: 758.

    Article  PubMed  Google Scholar 

  132. Katsel P, Davis KL, Haroutunian V . Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: a gene ontology study. Schizophr Res 2005; 79: 157–173.

    Article  PubMed  Google Scholar 

  133. Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 2000; 403: 434–439.

    Article  CAS  PubMed  Google Scholar 

  134. Josephson A, Widenfalk J, Widmer HW, Olson L, Spenger C . NOGO mRNA expression in adult and fetal human and rat nervous tissue and in weight drop injury. Exp Neurol 2001; 169: 319–328.

    Article  CAS  PubMed  Google Scholar 

  135. Novak G, Kim D, Seeman P, Tallerico T . Schizophrenia and Nogo: elevated mRNA in cortex, and high prevalence of a homozygous CAA insert. Brain Res Mol Brain Res 2002; 107: 183–189.

    Article  CAS  PubMed  Google Scholar 

  136. Gregorio SP, Mury FB, Ojopi EB, Sallet PC, Moreno DH, Yacubian J et al. Nogo CAA 3′UTR Insertion polymorphism is not associated with Schizophrenia nor with bipolar disorder. Schizophr Res 2005; 75: 5–9.

    Article  PubMed  Google Scholar 

  137. Xiong L, Rouleau GA, Delisi LE, St-Onge J, Najafee R, Riviere JB et al. CAA insertion polymorphism in the 3′UTR of Nogo gene on 2p14 is not associated with schizophrenia. Brain Res Mol Brain Res 2005; 133: 153–156.

    Article  CAS  PubMed  Google Scholar 

  138. Tan EC, Chong SA, Wang H, Chew-Ping Lim E, Teo YY . Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. Brain Res Mol Brain Res 2005; 139: 212–216.

    Article  CAS  PubMed  Google Scholar 

  139. Covault J, Lee J, Jensen K, Kranzler H . Nogo 3′-untranslated region CAA insertion: failure to replicate association with schizophrenia and demonstration of marked population difference in frequency of the insertion. Brain Res Mol Brain Res 2004; 120: 197–200.

    Article  CAS  PubMed  Google Scholar 

  140. Novak G, Tallerico T . Nogo A, B and C expression in schizophrenia, depression and bipolar frontal cortex, and correlation of Nogo expression with CAA/TATC polymorphism in 3′-UTR. Brain Res 2006; 1120: 161–171.

    Article  CAS  PubMed  Google Scholar 

  141. Sinibaldi L, De Luca A, Bellacchio E, Conti E, Pasini A, Paloscia C et al. Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia. Hum Mutat 2004; 24: 534–535.

    Article  PubMed  CAS  Google Scholar 

  142. Aberg K, Saetre P, Lindholm E, Ekholm B, Pettersson U, Adolfsson R et al. Human QKI, a new candidate gene for schizophrenia involved in myelination. Am J Med Genet B Neuropsychiatr Genet 2006; 141: 84–90.

    Article  CAS  Google Scholar 

  143. Li ZZ, Kondo T, Murata T, Ebersole TA, Nishi T, Tada K et al. Expression of Hqk encoding a KH RNA binding protein is altered in human glioma. Jpn J Cancer Res 2002; 93: 167–177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Lindholm E, Ekholm B, Shaw S, Jalonen P, Johansson G, Pettersson U et al. A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees. Am J Hum Genet 2001; 69: 96–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ekelund J, Lichtermann D, Hovatta I, Ellonen P, Suvisaari J, Terwilliger JD et al. Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22. Hum Mol Genet 2000; 9: 1049–1057.

    Article  CAS  PubMed  Google Scholar 

  146. Faraone SV, Matise T, Svrakic D, Pepple J, Malaspina D, Suarez B et al. Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium. Am J Med Genet 1998; 81: 290–295.

    Article  CAS  PubMed  Google Scholar 

  147. Levinson DF, Mahtani MM, Nancarrow DJ, Brown DM, Kruglyak L, Kirby A et al. Genome scan of schizophrenia. Am J Psychiatry 1998; 155: 741–750.

    CAS  PubMed  Google Scholar 

  148. Stober G, Saar K, Ruschendorf F, Meyer J, Nurnberg G, Jatzke S et al. Splitting schizophrenia: periodic catatonia-susceptibility locus on chromosome 15q15. Am J Hum Genet 2000; 67: 1201–1207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Barnea-Goraly N, Menon V, Krasnow B, Ko A, Reiss A, Eliez S . Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study. Am J Psychiatry 2003; 160: 1863–1869.

    Article  PubMed  Google Scholar 

  150. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET . Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000; 157: 16–25.

    Article  CAS  PubMed  Google Scholar 

  151. Shenton ME, Dickey CC, Frumin M, McCarley RW . A review of MRI findings in schizophrenia. Schizophr Res 2001; 49: 1–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kubicki M, McCarley R, Westin CF, Park HJ, Maier S, Kikinis R et al. A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res 2007; 41: 15–30.

    Article  PubMed  Google Scholar 

  153. Foong J, Maier M, Clark CA, Barker GJ, Miller DH, Ron MA . Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 2000; 68: 242–244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Agartz I, Andersson JL, Skare S . Abnormal brain white matter in schizophrenia: a diffusion tensor imaging study. Neuroreport 2001; 12: 2251–2254.

    Article  CAS  PubMed  Google Scholar 

  155. Buchsbaum MS, Tang CY, Peled S, Gudbjartsson H, Lu D, Hazlett EA et al. MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia. Neuroreport 1998; 9: 425–430.

    Article  CAS  PubMed  Google Scholar 

  156. Okugawa G, Nobuhara K, Minami T, Tamagaki C, Takase K, Sugimoto T et al. Subtle disruption of the middle cerebellar peduncles in patients with schizophrenia. Neuropsychobiology 2004; 50: 119–123.

    Article  PubMed  Google Scholar 

  157. Lim KO, Hedehus M, Moseley M, de Crespigny A, Sullivan EV, Pfefferbaum A . Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging. Arch Gen Psychiatry 1999; 56: 367–374.

    Article  CAS  PubMed  Google Scholar 

  158. Iwamoto K, Bundo M, Yamada K, Takao H, Iwayama-Shigeno Y, Yoshikawa T et al. DNA methylation status of SOX10 correlates with its downregulation and oligodendrocyte dysfunction in schizophrenia. J Neurosci 2005; 25: 5376–5381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Stolt CC, Rehberg S, Ader M, Lommes P, Riethmacher D, Schachner M et al. Terminal differentiation of myelin-forming oligodendrocytes depends on the transcription factor Sox10. Genes Dev 2002; 16: 165–170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Iwamoto K, Bundo M, Yamada K, Takao H, Iwayama Y, Yoshikawa T et al. A family-based and case-control association study of SOX10 in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2006; 141: 477–481.

    Article  CAS  Google Scholar 

  161. Murphy BC, O'Reilly RL, Singh SM . Site-specific cytosine methylation in S-COMT promoter in 31 brain regions with implications for studies involving schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2005; 133: 37–42.

    Article  Google Scholar 

  162. Costa E, Grayson DR, Guidotti A . Epigenetic downregulation of GABAergic function in schizophrenia: potential for pharmacological intervention? Mol Interv 2003; 3: 220–229.

    Article  CAS  PubMed  Google Scholar 

  163. Petronis A . The genes for major psychosis: aberrant sequence or regulation? Neuropsychopharmacology 2000; 23: 1–12.

    Article  CAS  PubMed  Google Scholar 

  164. Petronis A . Human morbid genetics revisited: relevance of epigenetics. Trends Genet 2001; 17: 142–146.

    Article  CAS  PubMed  Google Scholar 

  165. Abdolmaleky HM, Smith CL, Faraone SV, Shafa R, Stone W, Glatt SJ et al. Methylomics in psychiatry: modulation of gene-environment interactions may be through DNA methylation. Am J Med Genet B Neuropsychiatr Genet 2004; 127: 51–59.

    Article  Google Scholar 

  166. Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M, Assadzadeh A, Schumacher A et al. Intra- and interindividual epigenetic variation in human germ cells. Am J Hum Genet 2006; 79: 67–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Petronis A . The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis. Biol Psychiatry 2004; 55: 965–970.

    Article  CAS  PubMed  Google Scholar 

  168. Singh SM, Murphy B, O'Reilly RL . Involvement of gene-diet/drug interaction in DNA methylation and its contribution to complex diseases: from cancer to schizophrenia. Clin Genet 2003; 64: 451–460.

    Article  CAS  PubMed  Google Scholar 

  169. Popendikyte V, Laurinavicius A, Paterson AD, Macciardi F, Kennedy JL, Petronis A . DNA methylation at the putative promoter region of the human dopamine D2 receptor gene. Neuroreport 1999; 10: 1249–1255.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Alwin Prem Anand A, Dr Kerstin Schwabe and Prof Thomas Huber for their helpful discussions in revising the manuscript. Special thanks to the reviewers for their critical and most helpful suggestions.

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  1. Department of Clinical Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany

    G Karoutzou, H M Emrich & D E Dietrich

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Karoutzou, G., Emrich, H. & Dietrich, D. The myelin-pathogenesis puzzle in schizophrenia: a literature review. Mol Psychiatry 13, 245–260 (2008). https://doi.org/10.1038/sj.mp.4002096

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