Der Nervenarzt

, Volume 80, Issue 1, pp 40–53

Korrelation zwischen Risikogenvarianten für Schizophrenie und Hirnstrukturanomalien

Übersichten

Zusammenfassung

Die genauen Ätiologien der Schizophrenie sind noch weitgehend unklar. Genetische Faktoren stellen wichtige – wenngleich nicht alleinige – Risikofaktoren für die Entwicklung einer Schizophrenie dar. In den letzten Jahren konnten erstmals zahlreiche replizierbare Kandidatengene identifiziert werden. Magnetresonanztomographische Studien konnten strukturelle Gehirnveränderungen charakterisieren, so etwa Ventrikelerweiterungen oder Volumenminderungen der medialen temporalen Strukturen und des Gyrus temporalis superior. Mehrere Studien haben Korrelationen zwischen Genvarianten und hirnstrukturellen Veränderungen bei Gesunden und Schizophrenen nachgewiesen. In dieser Übersicht werden die bisher publizierten Arbeiten zur Korrelation von Varianten in Schizophreniesuszeptibilitätsgenen und Hirnstrukturanomalien bei Patienten und Gesunden referiert. Ziel ist es, eine Übersicht über den momentanen Stand dieser Forschungsrichtung zu geben und diese kritisch zu reflektieren. Durch die Ergebnisse der genomweiten Untersuchungen wird in Bälde eine Vielzahl weiterer Suszeptibilitätsgene für Schizophrenie bekannt werden. Ob und in welchem Ausmaß diese Gene einen Einfluss auf die Hirnstruktur bei Gesunden und Erkrankten haben, kann durch die Untersuchung von Gen-Struktur-Korrelationen geklärt werden. In Anbetracht der vielfältigen möglichen Gen-Gen- und Gen-Umwelt-Interaktionen ist allerdings bei den meisten Varianten davon auszugehen, dass keine einfachen Korrelationen mit großen Effekten gefunden werden können.

Schlüsselwörter

Endophänotyp Schizophrenie Strukturbildgebung Gen Polymorphismus 

Correlations between risk gene variants for schizophrenia and brain structure anomalies

Summary

The specific etiologies of schizophrenia are largely unknown. Genetic predisposition constitutes an important, however, not exclusive risk factor for the development of schizophrenia. In recent years, a number of candidate genes were identified and have been consistently replicated. Magnetic resonance imaging studies have characterized structural changes in brain morphology, such as ventricular enlargement or volume reduction of the medial temporal structures and the superior temporal gyrus. Several studies have found correlations between gene variants and changes of brain morphology in schizophrenia patients and healthy controls. In this review, publications examining correlations of schizophrenia susceptibility gene polymorphisms and structural brain anomalies in patients and healthy controls are described. An overview and a critical reflection of the current research are outlined. The results of genome-wide studies will soon provide a multitude of additional schizophrenia susceptibility genes. If and to what extent these genes exert an influence on the brain structure in the healthy and the diseased, can be clarified by gene structure correlations. Given the many possible gene-gene and gene-environment interactions, most variants will probably not show simple interactions with sizable effects.

Keywords

Endophenotype Schizophrenia Structural imaging Gene Polymorphism 

Literatur

  1. 1.
    Addington AM, Gornick MC, Shaw P et al. (2007) Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories. Mol Psychiatry 12: 195–205PubMedCrossRefGoogle Scholar
  2. 2.
    Altshuler LL, Bartzokis G, Grieder T et al. (1998) Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry 55(7): 663–664PubMedCrossRefGoogle Scholar
  3. 3.
    Badner JA, Gershon ES (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7(4): 405–411PubMedCrossRefGoogle Scholar
  4. 4.
    Becker T, Elmer K, Mechela B et al. (1990) MRI findings in medial temporal lobe structures in schizophrenia. Eur Neuropsychopharmacol 1(1): 83–86PubMedCrossRefGoogle Scholar
  5. 5.
    Bernstein HG, Lendeckel U, Bertram I et al. (2006) Localization of neuregulin-1alpha (heregulin-alpha) and one of its receptors, ErbB-4 tyrosine kinase, in developing and adult human brain. Brain Res Bull 69(5): 546–559PubMedCrossRefGoogle Scholar
  6. 6.
    Bilder RM, Wu H, Chakos MH et al. (1994) Cerebral morphometry and clozapine treatment in schizophrenia. J Clin Psychiatry 55 [Suppl B]: 53–56Google Scholar
  7. 7.
    Bogerts B, Ashtari M, Degreef G et al. (1990) Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Res 35(1): 1–13PubMedCrossRefGoogle Scholar
  8. 8.
    Boos HB, Aleman A, Cahn W et al. (2007) Brain volumes in relatives of patients with schizophrenia: a meta-analysis. Arch Gen Psychiatry 64(3): 297–304PubMedCrossRefGoogle Scholar
  9. 9.
    Brown AS (2006) Prenatal infection as a risk factor for schizophrenia. Schizophr Bull 32(2): 200–202PubMedCrossRefGoogle Scholar
  10. 10.
    Buonanno A, Fischbach GD (2006) Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 11: 287–296CrossRefGoogle Scholar
  11. 11.
    Callicott JH, Straub RE, Pezawas L et al. (2005) Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci U S A 102(24): 8627–8632PubMedCrossRefGoogle Scholar
  12. 12.
    Camargo LM, Collura V, Rain JC et al. (2007) Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Mol Psychiatry 12(1): 74–86PubMedCrossRefGoogle Scholar
  13. 13.
    Cannon TD, Rosso IM, Hollister JM et al. (2000) A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia. Schizophr Bull 26(2): 351–366PubMedGoogle Scholar
  14. 14.
    Cardno AG, Gottesman II (2000) Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 97(1): 12–17PubMedCrossRefGoogle Scholar
  15. 15.
    Chakos MH, Lieberman JA, Bilder RM et al. (1994) Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 151(10): 1430–1436PubMedGoogle Scholar
  16. 16.
    Chen X, Wang X, O’Neill AF et al. (2004) Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. Mol Psychiatry 9(10): 962–967PubMedCrossRefGoogle Scholar
  17. 17.
    Chumakov I, Blumenfeld M, Guerassimenko O et al. (2001) Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci U S A 99(21): 13675–13680CrossRefGoogle Scholar
  18. 18.
    Copolov D, Velakoulis D, McGorry P et al. (2000) Neurobiological findings in early phase schizophrenia. Brain Res Brain Res Rev 31(2–3): 157–165Google Scholar
  19. 19.
    Craddock N, Owen MJ, O’Donovan MC (2006) The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry 11(5): 446–458PubMedCrossRefGoogle Scholar
  20. 20.
    Crespo-Facorro B, Roiz-Santiáñez R, Pelayo-Terán JM et al. (2007) Low-activity allele of catechol-O-methyltransferase (COMTL) is associated with increased lateral ventricles in patients with first episode non-affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry 31(7): 1514–1518PubMedCrossRefGoogle Scholar
  21. 21.
    Detera-Wadleigh SD, McMahon FJ (2006) G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol Psychiatry 60(2): 106–114PubMedCrossRefGoogle Scholar
  22. 22.
    Dranovsky A, Hen R (2007) DISC1 puts the brakes on neurogenesis. Cell 130(6): 981–983PubMedCrossRefGoogle Scholar
  23. 23.
    Duan J, Martinez M, Sanders AR et al. (2007) DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3’ end of the gene. Hum Hered 64(2): 97–106PubMedCrossRefGoogle Scholar
  24. 24.
    Egan MF, Goldberg TE, Kolachana BS et al. (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 98(12): 6917–6922PubMedCrossRefGoogle Scholar
  25. 25.
    Falkai P, Honer WG, Kamer T et al. (2007) Disturbed frontal gyrification within families affected with schizophrenia. J Psychiatr Res 41(10): 805–813PubMedCrossRefGoogle Scholar
  26. 26.
    Fan JB, Zhang CS, Gu NF et al. (2005) Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol Psychiatry 57(2): 139–144PubMedCrossRefGoogle Scholar
  27. 27.
    Flaum M, O’Leary DS, Swayze VW 2nd et al. (1995) Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders. J Psychiatr Res 29(4): 261–276PubMedCrossRefGoogle Scholar
  28. 28.
    Fukuzako H, Yamada K, Kodama S et al. (1997) Hippocampal volume asymmetry and age at illness onset in males with schizophrenia. Eur Arch Psychiatry Clin Neurosci 247(5): 248–251PubMedCrossRefGoogle Scholar
  29. 29.
    Goghari VM, Sponheim SR (2008) Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder. Schizophren Res 103(1–3): 186–191Google Scholar
  30. 30.
    Goldberg TE, Egan MF, Gscheidle T et al. (2003) Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 60(9): 889–896PubMedCrossRefGoogle Scholar
  31. 31.
    Gratacòs M, González JR, Mercader JM et al. (2007) Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirms association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 61(7): 911–922PubMedCrossRefGoogle Scholar
  32. 32.
    Gur RE, Turetsky BI, Cowell PE et al. (2000) Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiatry 57(8): 769–775PubMedCrossRefGoogle Scholar
  33. 33.
    Hänninen K, Katila H, Saarela M et al. (2008) Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci 258(1): 10–15PubMedCrossRefGoogle Scholar
  34. 34.
    Haren NE van, Pol HE, Schnack HG et al. (2008) Progressive brain volume loss in schizophrenia over the course of the illness: evidence of maturational abnormalities in early adulthood. Biol Psychiatry 63(1): 106–113PubMedCrossRefGoogle Scholar
  35. 35.
    Harrison PJ, Weinberger DR (2005) Schizophrenia: genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10: 40–68PubMedCrossRefGoogle Scholar
  36. 36.
    Hennah W, Varilo T, Kestilä M et al. (2003) Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum Mol Genet 12: 3151–3159PubMedCrossRefGoogle Scholar
  37. 37.
    Henquet C, Murray R, Linszen D, Os J van (2005) The environment and schizophrenia: the role of cannabis use. Schizophr Bull 31(3): 608–612PubMedCrossRefGoogle Scholar
  38. 38.
    Ho BC, Andreasen NC, Nopoulos P et al. (2003) Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia. Arch Gen Psychiatry 60(6): 585–594PubMedCrossRefGoogle Scholar
  39. 39.
    Ho BC, Wassink TH, O’Leary DS et al. (2005) Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow. Mol Psychiatry10(3): 229: 287–298Google Scholar
  40. 40.
    Hodgkinson CA, Goldman D, Jaeger J et al. (2004) Disrupted in Schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet 75: 862–872PubMedCrossRefGoogle Scholar
  41. 41.
    Hong J, Shu-Leong H, Tao X, Lap-Ping Y (1998) Distribution of catechyl-O-methyltransferase expression in human central nervous system. Neuroreport 9(12): 2861–2864PubMedCrossRefGoogle Scholar
  42. 42.
    Kanazawa T, Glatt SJ, Kia-Keating B et al. (2007) Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder. Psychiatr Genet 17(3): 165–170PubMedCrossRefGoogle Scholar
  43. 43.
    Katila H, Appelberg B, Hurme M, Rimón R (1994) Plasma levels of interleukin-1 beta and interleukin-6 in schizophrenia, other psychoses, and affective disorders. Schizophr Res 12(1): 29–34PubMedCrossRefGoogle Scholar
  44. 44.
    Katila H, Hänninen K, Hurme M (1999) Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry 4: 179–181PubMedCrossRefGoogle Scholar
  45. 45.
    Keshavan MS, Bagwell WW, Haas GL et al. (1994) Changes in caudate volume with neuroleptic treatment. Lancet 344(8934): 1434PubMedCrossRefGoogle Scholar
  46. 46.
    Kim SJ, Lee HJ, Koo HG et al. (2004) Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder. Psychiatr Genet 14: 165–167PubMedCrossRefGoogle Scholar
  47. 47.
    Kircher T, Gauggel S (2007) Neuropsychologie der Schizophrenie. Springer, Berlin Heidelberg New York TokioGoogle Scholar
  48. 48.
    Kirov G, Murphy KC, Arranz MJ et al. (1998) Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder. Mol Psychiatry 3(4): 342–345PubMedCrossRefGoogle Scholar
  49. 49.
    Laurent C, Thibaut F, Ravassard P et al. (1997) Detection of two new polymorphic sites in the human interleukin-1 beta gene: lack of association with schizophrenia in a French population. Psychiatr Genet 7(3): 103–105PubMedCrossRefGoogle Scholar
  50. 50.
    Law AJ, Weickert CS, Hyde TM et al. (2004) Neuregulin-1 (NRG1) messenger RNA and protein in the human brain: hippocampal formation, prefrontal cortex, cerebellum and brainstem. Neuroscience 127: 125–136PubMedCrossRefGoogle Scholar
  51. 51.
    Lawrie SM, Whalley HC, Abukmeil SS et al. (2001) Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia. Biol Psychiatry 49(10): 811–823PubMedCrossRefGoogle Scholar
  52. 52.
    Leube DT, Rapp A, Buchkremer G et al. (2003) Hippocampal dysfunction during episodic memory encoding in patients with schizophrenia – an fMRI study. Schizophr Res 64(1): 83–85PubMedCrossRefGoogle Scholar
  53. 53.
    Lewis CM, Levinson DF, Wise LH et al. (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet 73(1): 34–48PubMedCrossRefGoogle Scholar
  54. 54.
    Li D, Collier DA, He L (2006) Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.Hum Mol Genet 15(12): 1995–2002PubMedCrossRefGoogle Scholar
  55. 55.
    Li T, Zhang F, Liu X et al. (2005) Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. Mol Psychiatry 10(11): 1037–1044PubMedCrossRefGoogle Scholar
  56. 56.
    Liu D, Diorio J, Day JC et al. (2000) Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci 3(8): 799–806PubMedCrossRefGoogle Scholar
  57. 57.
    López-Bendito G, Cautinat A, Sánchez JA et al. (2006) Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell 125(1): 127–142PubMedCrossRefGoogle Scholar
  58. 58.
    Lotta T, Vidgren J, Tilgmann C et al. (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34(13): 4202–4210PubMedCrossRefGoogle Scholar
  59. 59.
    Mannistö PT, Kaakkola S (1999) Catechyl-O-methyltransferase: biochemistry, molecular biology, pharmacology, and clinical efficacy of the new COMT inhibitors. Pharmacol Rev 51(4): 593–628PubMedGoogle Scholar
  60. 60.
    Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A (2001) Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 58(2): 148–157PubMedCrossRefGoogle Scholar
  61. 61.
    Matsumoto M, Weickert CS, Akil M et al. (2003) Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience 116(1): 127–137PubMedCrossRefGoogle Scholar
  62. 62.
    McIntosh AM, Baig BJ, Hall J et al. (2007) Relationship of catechol-O-methyltransferase variants to brain structure and function in a population at high risk of psychosis. Biol Psychiatry 61(10): 1127–1134PubMedCrossRefGoogle Scholar
  63. 63.
    McIntosh AM, Moorhead TW, Job D et al. (2007) The effects of a neuregulin 1 variant on white matter density and integrity. Mol Psychiatry 2007 Oct 9 [Epub ahead of print]Google Scholar
  64. 64.
    Meisenzahl EM, Rujescu D, Kirner A et al. (2001) Association of an interleukin-1beta genetic polymorphism with altered brain structure in patients with schizophrenia. Am J Psychiatry 158(8): 1316–1319PubMedCrossRefGoogle Scholar
  65. 65.
    Melle I, Larsen TK, Haahr U et al. (2008) Prevention of negative symptom psychopathologies in first-episode schizophrenia: two-year effects of reducing the duration of untreated psychosis. Arch Gen Psychiatry 65(6): 634–640PubMedCrossRefGoogle Scholar
  66. 66.
    Meyer-Lindenberg A, Nicodemus KK, Egan MF et al. (2008) False positives in imaging genetics. Neuroimage 40(2): 655–661PubMedCrossRefGoogle Scholar
  67. 67.
    Millar JK, Wilson-Annan JC, Anderson S et al. (2000) Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 9(9): 1415–1423PubMedCrossRefGoogle Scholar
  68. 68.
    Mirnics K, Middleton FA, Stanwood GD et al. (2001) Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 6(3): 293–301PubMedCrossRefGoogle Scholar
  69. 69.
    Mukherjee N, Kidd KK, Pakstis AJ et al. (2008) The complex global pattern of genetic variation and linkage disequilibrium at catechol-O-methyltransferase. Mol Psychiatry, DOI 10.1038/mp.2008.64Google Scholar
  70. 70.
    Munro CA, McCaul ME, Wong DF et al. (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry 59(10): 966–974PubMedCrossRefGoogle Scholar
  71. 71.
    Mutsuddi M, Morris DW, Waggoner SG et al. (2006) Analysis of high-resolution HapMap of DTNBP1 (Dysbindin) suggests no consistency between reported common variant associations and schizophrenia. Am J Hum Genet 79(5): 903–909PubMedCrossRefGoogle Scholar
  72. 72.
    Nackley AG, Shabalina SA, Tchivileva IE et al. (2006) Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314(5807): 1930–1933PubMedCrossRefGoogle Scholar
  73. 73.
    Nawa H, Takei M (2006) Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 56(1): 2–13PubMedCrossRefGoogle Scholar
  74. 74.
    Nicklin MJ, Barton JL, Nguyen M et al. (2002) A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics 79(5): 718–725PubMedCrossRefGoogle Scholar
  75. 75.
    Nicodemus KK, Kolachana BS, Vakkalanka R et al. (2007) Evidence for statistical epistasis between catechol-O-methyltransferase (COMT) and polymorphisms in RGS4, G72 (DAOA), GRM3, and DISC1: influence on risk of schizophrenia. Hum Genet 120: 889–906PubMedCrossRefGoogle Scholar
  76. 76.
    Ockel M, Lewin GR, Barde YA (1996) In vivo effects of neurotrophin-3 during sensory neurogenesis. Development 122(1): 301–307PubMedGoogle Scholar
  77. 77.
    Ohnishi T, Hashimoto R, Mori T et al. (2006) The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 129: 399–410PubMedCrossRefGoogle Scholar
  78. 78.
    Oord EJ van den, Sullivan PF, Jiang Y et al. (2003) Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families. Mol Psychiatry 8(5): 499–510PubMedCrossRefGoogle Scholar
  79. 79.
    Os J van, Krabbendam L, Myin-Germeys I, Delespaul P (2005) The schizophrenia envirome. Curr Opin Psychiatry 18(2): 141–145PubMedCrossRefGoogle Scholar
  80. 80.
    Papiol S, Molina V, Desco M et al. (2005) Ventricular enlargement in schizophrenia is associated with a genetic polymorphism at the interleukin-1 receptor antagonist gene. Neuroimage 27(4): 1002–1006PubMedCrossRefGoogle Scholar
  81. 81.
    Papolos DF, Veit S, Faedda GL et al. (1998) Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele. Mol Psychiatry 3(4): 346–349PubMedCrossRefGoogle Scholar
  82. 82.
    Pantelis C, Velakoulis D, McGorry PD et al. (2003) Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361(9354): 281–288PubMedCrossRefGoogle Scholar
  83. 83.
    Pantelis C, Velakoulis D, Wood SJ et al. (2007) Neuroimaging and emerging psychotic disorders: the Melbourne ultra-high risk studies. Int Rev Psychiatry 19(4): 371–381PubMedCrossRefGoogle Scholar
  84. 84.
    Prasad KM, Chowdari KV, Nimgaonkar VL et al. (2005) Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients. Mol Psychiatry 10(2): 213–219PubMedCrossRefGoogle Scholar
  85. 85.
    Roysommuti S, Carroll SL, Wyss JM (2003) Neuregulin-1b modulates in vivo entorhinal–hippocampal synaptic transmission in adult rats. Neuroscience 121: 779–785PubMedCrossRefGoogle Scholar
  86. 86.
    Rujescu D, Meisenzahl EM, Krejcova S et al. (2007) Plexin B3 is genetically associated with verbal performance and white matter volume in human brain. Mol Psychiatry 12: 190–194PubMedCrossRefGoogle Scholar
  87. 87.
    Saux M le, Morissette M, Paolo T di (2006) ERbeta mediates the estradiol increase of D2 receptors in rat striatum and nucleus accumbens. Neuropharmacology 50(4): 451–457PubMedCrossRefGoogle Scholar
  88. 88.
    Scherk H, Falkai P (2004) Veränderungen der Hirnstruktur durch neuroleptische Medikation. Nervenarzt 75(11): 1112–1117PubMedCrossRefGoogle Scholar
  89. 89.
    Scherk H, Falkai P (2006) Effects of antipsychotics on brain structure. Curr Opin Psychiatry 19(2): 145–150PubMedCrossRefGoogle Scholar
  90. 90.
    Schumacher J, Jamra RA, Becker T et al. (2005) Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 58(4): 307–314PubMedCrossRefGoogle Scholar
  91. 91.
    Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophr Res 49(1–2): 1–52Google Scholar
  92. 92.
    Shi J, Badner JA, Gershon ES, Liu C (2008) Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis. Schizophr Res 98(1–3): 89–97Google Scholar
  93. 93.
    Shirts BH, Wood J, Yolken RH, Nimgaonkar VL (2006) Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta. Schizophr Res 88(1–3): 235–244Google Scholar
  94. 94.
    Sporn AL, Greenstein DK, Gogtay N et al. (2003) Progressive brain volume loss during adolescence in childhood-onset schizophrenia. Am J Psychiatry 160(12): 2181–2189PubMedCrossRefGoogle Scholar
  95. 95.
    St Clair D, Blackwood D, Muir W et al. (1990) Association within a family of a balanced autosomal translocation with major mental illness. Lancet 336: 13–16CrossRefGoogle Scholar
  96. 96.
    Stefanis N, Frangou S, Yakeley J et al. (1999) Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biol Psychiatry 46(5): 697–702PubMedCrossRefGoogle Scholar
  97. 97.
    Stefanis NC, Os J van, Avramopoulos D et al. (2004) Variation in catechol-o-methyltransferase val158 met genotype associated with schizotypy but not cognition: a population study in 543 young men. Biol Psychiatry 56(7): 510–515PubMedCrossRefGoogle Scholar
  98. 98.
    Stefansson H, Sigurdsson E, Steinthorsdottir V et al. (2002) Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71(4): 877–892PubMedCrossRefGoogle Scholar
  99. 99.
    Stoop R, Poo MM (2006) Synaptic modulation by neurotrophic factors: differential and synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor. J Neurosci 16(10): 3256–3264Google Scholar
  100. 100.
    Straub RE, Jiang Y, MacLean CJ et al. (2002) Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am J Hum Genet 71(2): 337–348PubMedCrossRefGoogle Scholar
  101. 101.
    Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 60(12): 1187–1192PubMedCrossRefGoogle Scholar
  102. 102.
    Szeszko PR, Lipsky R, Mentschel C (2005) Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol Psychiatry 10(7): 631–636PubMedCrossRefGoogle Scholar
  103. 103.
    Talkowski ME, Seltman H, Bassett AS et al. (2006) Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples. Biol Psychiatry 60(2): 152–162PubMedCrossRefGoogle Scholar
  104. 104.
    Tamagnone L, Artigiani S, Chen H et al. (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99(1): 71–80PubMedCrossRefGoogle Scholar
  105. 105.
    Tan HY, Callicott JH, Weinberger DR (2007) Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cereb Cortex 17 [Suppl 1]: i171–i181Google Scholar
  106. 106.
    Taylor WD, Züchner S, Payne ME et al. (2007) The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults. Psychiatry Res 155(2): 173–177PubMedCrossRefGoogle Scholar
  107. 107.
    Taymans JM, Wintmolders C, Te Riele P et al. (2002) Detailed localization of regulator of G protein signaling 2 messenger ribonucleic acid and protein in the rat brain. Neuroscience 114(1): 39–53PubMedCrossRefGoogle Scholar
  108. 108.
    Tenhunen J, Salminen M, Lundström K et al. (1994) Genomic organization of the human catechol O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem 223(3): 1049–1059PubMedCrossRefGoogle Scholar
  109. 109.
    Thaminy S, Auerbach D, Arnoldo A, Stagljar I (2003) Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system. Genome Res 13: 1744–1753PubMedCrossRefGoogle Scholar
  110. 110.
    Thomson PA, Wray NR, Millar JK et al. (2005) Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population. Mol Psychiatry 10: 657–668PubMedCrossRefGoogle Scholar
  111. 111.
    Tosato S, Dazzan P, Collier D (2005) Association between the neuregulin 1 gene and schizophrenia: a systematic review. Schizophr Bull 31(3): 613–617PubMedCrossRefGoogle Scholar
  112. 112.
    Tsai G, Passani LA, Slusher BS et al. (1995) Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch Gen Psychiatry 52: 829–836PubMedGoogle Scholar
  113. 113.
    Tsai G, Kammen DP van, Chen S et al. (1998) Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia. Biol Psychiatry 44: 667–674PubMedCrossRefGoogle Scholar
  114. 114.
    Vries L de, Zheng B, Fischer T et al. (2000) The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 40: 235–271PubMedCrossRefGoogle Scholar
  115. 115.
    Watanabe Y, Nunokawa A, Kaneko N et al. (2007) Lack of association between the interleukin-1 gene complex and schizophrenia in a Japanese population. Psychiatry Clin Neurosci 61: 364–369PubMedCrossRefGoogle Scholar
  116. 116.
    Weinberger DR (1999) Cell biology of the hippocampal formation in schizophrenia. Biol Psychiatry 45(4): 395–402PubMedCrossRefGoogle Scholar
  117. 117.
    Weinberger DR, Egan MF, Bertolino A et al. (2001) Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 50(11): 825–44PubMedCrossRefGoogle Scholar
  118. 118.
    Weinshilboum RM, Otterness DM, Szumlanski CL (1999) Methylation pharmacogenetics: catechol-o-methyltransferase, thiopurine methyltransferase, and histamine-N-methyltransferase. Annu Rev Pharmacol Toxicol 39: 19–52PubMedCrossRefGoogle Scholar
  119. 119.
    Williams NM, Preece A, Morris DW et al. (2004) Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1). Arch Gen Psychiatry 61(4): 336–344PubMedCrossRefGoogle Scholar
  120. 120.
    Winterer G, Weinberger DR (2004) Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 27: 683–690PubMedCrossRefGoogle Scholar
  121. 121.
    Wobrock T, Kamer T, Roy A et al. (2008) Reduction of the internal capsule in families affected with schizophrenia. Biol Psychiatry 63(1): 65–71PubMedCrossRefGoogle Scholar
  122. 122.
    Wood SJ, Yücel M, Velakoulis D et al. (2005) Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness. Schizophr Res 75(2–3): 295–301Google Scholar
  123. 123.
    Xu MQ, St Clair D, Ott J et al. (2007) Brain-derived neurotrophic factor gene C-270T and Val66Met functional polymorphisms and risk of schizophrenia: a moderate-scale population-based study and meta-analysis. Schizophr Res 91(1-3): 6–13Google Scholar
  124. 124.
    Xu MQ, St Clair D, Feng GY et al. (2008) BDNF gene is a genetic risk factor for schizophrenia and is related to the chlorpromazine-induced extrapyramidal syndrome in the Chinese population. Pharmacogenet Genomics 18(6): 449–457PubMedCrossRefGoogle Scholar
  125. 125.
    Zanardini R, Bocchio-Chiavetto L, Scassellati C et al. (2003) Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia. J Psychiatr Res 37: 457–462PubMedCrossRefGoogle Scholar
  126. 126.
    Zhang F, Sarginson J, Crombie C et al. (2006) Genetic association between schizophrenia and the DISC1 gene in the Scottish population. Am J Med Genet B Neuropsychiatr Genet 141: 155–159Google Scholar
  127. 127.
    Zinkstok J, Schmitz N, Amelsvoort van T et al. (2007) The COMT val158met polymorphism and brain morphometry in healthy young adults. Neurosci Lett 405(1–2): 34–39Google Scholar

Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.Klinik für Psychiatrie und PsychotherapieUniversitätsklinikum RWTH AachenAachenDeutschland
  2. 2.Institut für Neurowissenschaften und Biophysik-3Forschungszentrum JülichJülichDeutschland
  3. 3.Zentralinstitut für Seelische GesundheitMannheimDeutschland

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