Skip to main content

Abstract

Various studies show, that a longer duration of untreated psychosis relates to a worse prognosis. Thus the early recognition of schizophrenia seems a crucial challenge. However, many clinical symptoms of prodromal schizophrenia stages are not sufficiently specific. Here we present an overview over recent contributions of neuroimaging and electrophysiological as well as genetic studies: Which additional information offer endophenotypes (such as P300, P50 sensory gating, MMN, smooth pursuit eye movements; indicating a specific genetic vulnerability) together with a better understanding of schizophrenic pathophysiology (state-dependent biological markers, e.g. aggravated motor neurological soft signs during psychosis) in prodromal schizophrenia when still ambiguous clinical symptoms are present. Examples (e.g. from COMT polymorphisms to working memory deficits) are given to illustrate more specific underlying neuronal mechanisms behind behavioural symptoms. This way, a characteristic pattern of disturbed cerebral maturation might be distinguished in order to complement clinical instruments of early schizophrenia detection. While today, the specificity and sensitivity of the aforementioned markers does still not allow diagnosing all the heterogeneous forms of the schizophrenic syndrome, it seems a promising approach to define specific high-risk constellations for subgroups of patients to allow timely early interventions when they are justified. The main focus of this chapter will be to connect clinical symptoms with genetic findings via endophenotypes and to give an impression how clinical early recognition attempts could be complemented by functional and structural endophenotypes that could serve as diagnostic markers. State markers and endophenotypes as a specific kind of trait marker are compared, possibilities and limitations with respect to sensitivity and specificity are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Mossaheb N, Wiesegger G, Amminger GP, Kasper S, Tauscher J. Früherkennung und Frühintervention der Schizophrenie. Nervenarzt 2006;77:23–34.

    PubMed  CAS  Google Scholar 

  2. Ho BC, Alicata D, Ward J, et al. Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. Am J Psychiatry 2003;160:142–148.

    PubMed  Google Scholar 

  3. Klosterkotter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F. Diagnosing schizophrenia in the initial prodromal phase. Arch Gen Psychiatry 2001;58:158–164.

    PubMed  CAS  Google Scholar 

  4. Yung A, Yuen H, McGorry PD, et al. Mapping the onset of psychosis: the comprehensive assessment of at-risk mental states. Aust N Z J Psychiatry 2005;39:964–971.

    PubMed  Google Scholar 

  5. Miller TJ, McGlashan TH, Rosen JL, et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability and training to reliability. Schizophr Bull 2003;29:703–715.

    PubMed  Google Scholar 

  6. Hafner H, Riecher-Rossler A, Hambrecht M, et al. IRAOS: an instrument for the assessment of onset and early course of schizophrenia. Schizophr Res 1992;6:209–223.

    PubMed  CAS  Google Scholar 

  7. Hafner H, Maurer K, Ruhrmann S, et al. Early detection and secondary prevention of psychosis: facts and visions. Eur Arch Psychiatry Clin Neurosci 2004;254:117–128.

    PubMed  Google Scholar 

  8. McGorry PD, Yung A, Phillips L, et al. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 2002; 59:921–928.

    PubMed  Google Scholar 

  9. Ruhrmann S, Schultze-Lutter F, Klosterkotter J. Early detection and intervention in the initial prodromal phase of schizophrenia. Pharmacopsychiatry 2003;36:S162–S167.

    PubMed  Google Scholar 

  10. Resch F, Koch E, Mohler E, Parzer P, Brunner R. Early detection of psychotic disorders in adolescents: specificity of basic symptoms in psychiatric patient samples. Psychopathology 2002;35:259–266.

    PubMed  CAS  Google Scholar 

  11. Schultze-Lutter F, Ruhrmann S, Picker H, von Reventlow HG, Brockhaus-Dumke A, Klosterkotter J. Basic symptoms in early psychotic and depressive disorders. Br J Psychiatry Suppl 2007;51:S31–37.

    PubMed  Google Scholar 

  12. Woods SW, Breier A, Zipursky RB, et al. Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biol Psychiatry 2003;54:453–464.

    PubMed  CAS  Google Scholar 

  13. Cornblatt BA, Lencz T, Kane JM. Treatment of the schizophrenia prodrome: is it presently ethical? Schizophr Res 2001;51:31–38.

    PubMed  CAS  Google Scholar 

  14. Verdoux H, Cougnard A. Schizophrenia: who is at risk? Who is a case? Int Clin Psychopharmacol 2006;21(Suppl 2):S17–19.

    PubMed  Google Scholar 

  15. Galderisi S, Maj M, Mucci A, et al. Historical, psychopatho-logical, neurological, and neuropsychological aspects of deficit schizophrenia: A multicenter study. Am J Psychiatry 2002;159:983–990.

    PubMed  Google Scholar 

  16. Holzman PS, Proctor LR, Hughes DW. Eye-tracking patterns in schizophrenia. Science 1973;181:179–181.

    PubMed  CAS  Google Scholar 

  17. Hegerl U, Juckel G. Auditory evoked dipole source activity: indicator of central serotonergic dysfunction in psychiatric patients? Pharmacopsychiatry 1994;27:75–78.

    PubMed  CAS  Google Scholar 

  18. Berrettini WH. Genetic bases for endophenotypes in psychiatric disorders. Dialogues Clin Neurosci 2005;7:95–101.

    PubMed  Google Scholar 

  19. Maier W, Hofgen B, Zobel A, Rietschel M. Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes? Eur Arch Psychiatry Clin Neurosci 2005;255:159–166.

    PubMed  Google Scholar 

  20. Beckmann H, Franzek E. The genetic heterogeneity of “schizophrenia”. World J Biol Psychiatry 2000;1:35–41.

    PubMed  CAS  Google Scholar 

  21. Verdoux H. Perinatal risk factors for schizophrenia: how specific are they? Curr Psychiatry Rep 2004;6:162–167.

    PubMed  Google Scholar 

  22. Cadenhead KS. Vulnerability markers in the schizophrenia spectrum: implications for phenomenology, genetics, and the identification of the schizophrenia prodrome. Psychiatr Clin North Am 2002;25:837–853.

    PubMed  Google Scholar 

  23. Price GW, Michie PT, Johnston J, et al. A multivariate elec-trophysiological endophenotype, from a unitary cohort, shows greater research utility than any single feature in the Western Australian family study of schizophrenia. Biol Psychiatry 2005;60:1–10.

    PubMed  Google Scholar 

  24. Weir N, Fiaschi K, Machin D. The distribution and latency of the auditory P300 in schizophrenia and depression. Schizophr Res 1998;31:151–158.

    PubMed  CAS  Google Scholar 

  25. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disor-ders-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.

    PubMed  CAS  Google Scholar 

  26. Flechtner KM, Steinacher B, Sauer R, Mackert A. Smooth pursuit eye movements in schizophrenia and affective disorder. Psychol Med 1997;27:1411–1419.

    PubMed  CAS  Google Scholar 

  27. Lencer R, Trillenberg P, Trillenberg-Krecker K, et al. Smooth pursuit deficits in schizophrenia, affective disorder and obsessive-compulsive disorder. Psychol Med 2004;34:451–460.

    PubMed  CAS  Google Scholar 

  28. Mahlberg R, Steinacher B, Mackert A, Flechtner KM. Basic parameters of saccadic eye movements—differences between unmedicated schizophrenia and affective disorder patients. Eur Arch Psychiatry Clin Neurosci 2001;251:205–210.

    PubMed  CAS  Google Scholar 

  29. Malaspina D, Amador XF, Coleman EA, Mayr TL, Friedman JH, Sackeim HA. Smooth pursuit eye movement abnormality in severe major depression: effects of ECT and clinical recovery. J Neuropsychiatry Clin Neurosci 1994;6:36–42.

    PubMed  CAS  Google Scholar 

  30. Muir WJ, St Clair DM, Blackwood DH, Roxburgh HM, Marshall I. Eye-tracking dysfunction in the affective psychoses and schizophrenia. Psychol Med 1992;22:573–580.

    PubMed  CAS  Google Scholar 

  31. Kathmann N, Hochrein A, Uwer R, Bondy B. Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives. Am J Psychiatry 2003;160:696–702.

    PubMed  Google Scholar 

  32. Rosenberg DR, Sweeney JA, Squires-Wheeler E, Keshavan MS, Cornblatt BA, Erlenmeyer-Kimling L. Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention. Psychiatry Res 1997;66:121–130.

    PubMed  CAS  Google Scholar 

  33. Bender S, Weisbrod M, Resch F. Which perspectives can endo-phenotypes and biological markers offer in the early recognition of schizophrenia? J Neural Transm 2007;114:1199–1215.

    PubMed  CAS  Google Scholar 

  34. van der Stelt O, Belger A. Application of electroencepha-lography to the study of cognitive and brain functions in schizophrenia. Schizophr Bull 2007;33:955–970.

    PubMed  Google Scholar 

  35. Lewis CM, Levinson DF, Wise LH, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 2003;73:34–48.

    PubMed  CAS  Google Scholar 

  36. Rapoport JL, Addington AM, Frangou S, Psych MR. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 2005;10:434–449.

    PubMed  CAS  Google Scholar 

  37. Kaiser S, Roth A, Rentrop M, Friederich HC, Bender S, Weisbrod M. Intra-individual reaction time variability in schizophrenia, depression and borderline personality disorder. Brain Cogn 2008;66:73–82.

    PubMed  Google Scholar 

  38. Roth A, Roesch-Ely D, Bender S, Weisbrod M, Kaiser S. Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis. Int J Psychophysiol 2007;66:244–254.

    PubMed  Google Scholar 

  39. Doniger GM, Foxe JJ, Murray MM, Higgins BA, Javitt DC. Impaired visual object recognition and dorsal/ventral stream interaction in schizophrenia. Arch Gen Psychiatry 2002;59:1011–1020.

    PubMed  Google Scholar 

  40. Addington AM, Gornick M, Duckworth J, 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.

    PubMed  CAS  Google Scholar 

  41. Woo TU, Walsh JP, Benes FM. Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. Arch Gen Psychiatry 2004;61:649–657.

    PubMed  CAS  Google Scholar 

  42. Kalkman HO, Loetscher E. GAD(67): the link between the GABA-deficit hypothesis and the dopaminergic and glu-taminergic theories of psychosis. J Neural Transm 2003;110:803–812.

    PubMed  CAS  Google Scholar 

  43. Volk DW, Lewis DA. Impaired prefrontal inhibition in schizophrenia: relevance for cognitive dysfunction. Physiol Behav 2002;77:501–505.

    PubMed  CAS  Google Scholar 

  44. Lewis DA, Volk DW, Hashimoto T. Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction. Psychopharmacology (Berl) 2004;174:143–150.

    CAS  Google Scholar 

  45. Daskalakis ZJ, Christensen BK, Chen R, Fitzgerald PB, Zipursky RB, Kapur S. Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation. Arch Gen Psychiatry 2002;59:347–354.

    PubMed  Google Scholar 

  46. Korostishevsky M, Kaganovich M, Cholostoy A, et al. Is the G72/G30 locus associated with schizophrenia? Single nucleotide polymorphisms, haplotypes, and gene expression analysis. Biol Psychiatry 2004;56:169–176.

    PubMed  CAS  Google Scholar 

  47. Korostishevsky M, Kremer I, Kaganovich M, et al. Transmission disequilibrium and haplotype analyses of the G72/G30 locus: Suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel. Am J Med Genet B Neuropsychiatr Genet 2006;141:91–95.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  49. Addington AM, Gornick M, Sporn AL, et al. Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified. Biol Psychiatry 2004;55:976–980.

    PubMed  CAS  Google Scholar 

  50. Egan MF, Straub RE, Goldberg TE, et al. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci USA 2004;101:12604–12609.

    PubMed  CAS  Google Scholar 

  51. Numakawa T, Yagasaki Y, Ishimoto T, et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004;13:2699–2708.

    PubMed  CAS  Google Scholar 

  52. Gornick MC, Addington AM, Sporn A, et al. Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS). J Autism Dev Disord. 2005;10:1–8.

    Google Scholar 

  53. Holzman PS, Kringlen E, Levy DL, Proctor LR, Haberman SJ, Yasillo NJ. Abnormal-pursuit eye movements in schizophrenia. Evidence for a genetic indicator. Arch Gen Psychiatry 1977;34:802–805.

    CAS  Google Scholar 

  54. Holzman PS, Kringlen E, Levy DL, Proctor LR, Haberman S. Smooth pursuit eye movements in twins discordant for schizophrenia. J Psychiatr Res 1978;14:111–120.

    PubMed  CAS  Google Scholar 

  55. Holzman PS, Kringlen E, Matthysse S, et al. A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins. Arch Gen Psychiatry 1988;45:641–647.

    PubMed  CAS  Google Scholar 

  56. Arolt V, Lencer R, Nolte A, 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.

    PubMed  CAS  Google Scholar 

  57. Matthysse S, Holzman PS, Gusella JF, et al. Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: additional evidence. Am J Med Genet B Neuropsychiatr Genet 2004;128:30–36.

    Google Scholar 

  58. Thaker G, Wonodi I, Avila MT, Hong LE, Stine OC. Catechol-O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report. Am J Psychiatry 2004;161:2320–2322.

    PubMed  Google Scholar 

  59. Rybakowski JK, Borkowska A, Czerski PM, Hauser J. Eye movement disturbances in schizophrenia and a polymorphism of catechol-O-methyltransferase gene. Psychiatry Res 2002;113:49–57.

    PubMed  CAS  Google Scholar 

  60. Rybakowski JK, Borkowska A, Czerski PM, Dmitrzak-Weglarz M, Hauser J. The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker. Neuropsychobiology 2003;47:115–119.

    PubMed  Google Scholar 

  61. Holzman PS. Eye movements and the search for the essence of schizophrenia. Brain Res Brain Res Rev 2000;31:350–356.

    PubMed  CAS  Google Scholar 

  62. Hong LE, Tagamets M, Avila MT, Wonodi I, Holcomb H, Thaker G. Specific motion processing pathway deficit during eye tracking in schizophrenia: a performance-matched functional magnetic resonance imaging study. Biol Psychiatry 2005;57:726–732.

    PubMed  Google Scholar 

  63. Thaker G, Ross DE, Cassady SL, et al. Smooth persuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia. Arch Gen Psychiatry 1998;55:830–836.

    PubMed  CAS  Google Scholar 

  64. Hutton S, Kennard C. Oculomotor abnormalities in schizophrenia: a critical review. Neurology 1998;50:604–609.

    PubMed  CAS  Google Scholar 

  65. Kumra S, Sporn A, Hommer DW, et al. Smooth pursuit eye-tracking impairment in childhood-onset psychotic disorders. Am J Psychiatry 2001;158:1291–1298.

    PubMed  CAS  Google Scholar 

  66. Ross RG, Olincy A, Harris JG, et al. Evidence for bilineal inheritance of physiological indicators of risk in childhood-onset schizophrenia. Am J Med Genet 1999;88:188–199.

    PubMed  CAS  Google Scholar 

  67. Ross RG, Olincy A, Mikulich SK, et al. Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading sacca-des are potential endophenotypes. Psychophysiology 2002;39:809–819.

    PubMed  Google Scholar 

  68. Sporn A, Greenstein D, Gogtay N, et al. Childhood-onset schizophrenia: smooth pursuit eye-tracking dysfunction in family members. Schizophr Res 2005;73:243–252.

    PubMed  Google Scholar 

  69. Ross RG, Olincy A, Harris JG, Sullivan B, Radant A. Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults with schizophrenia, ADHD, and a normal comparison group. Biol Psychiatry 2000;48:197–203.

    PubMed  CAS  Google Scholar 

  70. Ross RG, Heinlein S, Zerbe GO, Radant A. Saccadic eye movement task identifies cognitive deficits in children with schizophrenia, but not in unaffected child relatives. J Child Psychol Psychiatry 2005;46:1354–1362.

    PubMed  Google Scholar 

  71. Levy DL, O'Driscoll G, Matthysse S, Cook SR, Holzman PS, Mendell NR. Antisaccade performance in biological relatives of schizophrenia patients: a meta-analysis. Schizophr Res 2004;71:113–125.

    PubMed  Google Scholar 

  72. Calkins ME, Curtis CE, Iacono WG, Grove WM. Antisaccade performance is impaired in medically and psychiatrically healthy biological relatives of schizophrenia patients. Schizophr Res 2004;71:167–178.

    PubMed  Google Scholar 

  73. Fallgatter AJ, Herrmann MJ, Hohoff C, et al. DTNBP1 (Dysbindin) Gene variants modulate prefrontal brain function in healthy individuals. Neuropsychopharmacology 2006;31:2002–2010.

    PubMed  CAS  Google Scholar 

  74. Bramon E, McDonald C, Croft RJ, et al. Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study. Neuroimage 2005;27:960–968.

    PubMed  Google Scholar 

  75. Winterer G, Egan MF, Raedler T, et al. P300 and genetic risk for schizophrenia. Arch Gen Psychiatry 2003;60:1158–1167.

    PubMed  Google Scholar 

  76. Weisbrod M, Hill H, Niethammer R, Sauer H. Genetic influence on auditory information processing in schizophrenia: P300 in monozygotic twins. Biol Psychiatry 1999;46:721–725.

    PubMed  CAS  Google Scholar 

  77. McCarley RW, Salisbury DF, Hirayasu Y, et al. Association between smaller left posterior superior temporal gyrus volume on magnetic resonance imaging and smaller left temporal P300 amplitude in first-episode schizophrenia. Arch Gen Psychiatry 2002;59:321–331.

    PubMed  Google Scholar 

  78. Mathalon DH, Ford JM, Pfefferbaum A. Trait and state aspects of P300 amplitude reduction in schizophrenia: a retrospective longitudinal study. Biol Psychiatry 2000;47: 434–449.

    PubMed  CAS  Google Scholar 

  79. Higashima M, Nagasawa T, Kawasaki Y, et al. Auditory P300 amplitude as a state marker for positive symptoms in schizophrenia: cross-sectional and retrospective longitudinal studies. Schizophr Res 2003;59:147–157.

    PubMed  Google Scholar 

  80. Molina V, Munoz F, Martin-Loeches M, Casado P, Hinojosa JA, Iglesias A. Long-term olanzapine treatment and p300 parameters in schizophrenia. Neuropsychobiology 2004; 50:182–188.

    Google Scholar 

  81. van der Stelt O, Lieberman JA, Belger A. Auditory P300 in high-risk, recent-onset and chronic schizophrenia. Schizophr Res 2005;77:309–320.

    PubMed  Google Scholar 

  82. Bharath S, Gangadhar BN, Janakiramaiah N. P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol 2000;38:43–54.

    PubMed  CAS  Google Scholar 

  83. Weisbrod M, Kiefer M, Marzinzik F, Spitzer M. Executive control is disturbed in schizophrenia: evidence from event-related potentials in a Go/NoGo task. Biol Psychiatry 2000;47:51–60.

    PubMed  CAS  Google Scholar 

  84. Fanous AH, Kendler KS. Genetics of clinical features and subtypes of schizophrenia: a review of the recent literature. Curr Psychiatry Rep 2008;10:164–170.

    PubMed  Google Scholar 

  85. Seidman LJ, Faraone S V, Goldstein JM, et al. Left hip-pocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Arch Gen Psychiatry 2002;59:839–849.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  87. Powell KJ, Binder TL, Hori S, et al. Neonatal ventral hip-pocampal lesions produce an elevation of DeltaFosB-like protein(s) in the rodent neocortex. Neuropsychopharma-cology 2006;31:700–711.

    CAS  Google Scholar 

  88. Wong AH, Lipska BK, Likhodi O, et al. Cortical gene expression in the neonatal ventral-hippocampal lesion rat model. Schizophr Res 2005;77:261–270.

    PubMed  Google Scholar 

  89. Akil M, Kolachana BS, Rothmond DA, et al. Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci 2003;23:2008–2013.

    PubMed  CAS  Google Scholar 

  90. Eliez S, Schmitt JE, White CD, Reiss AL. Children and adolescents with velocardiofacial syndrome: a volumetric MRI study. Am J Psychiatry 2000;157:409–415.

    PubMed  CAS  Google Scholar 

  91. Egan MF, Goldberg TE, Kolachana BS, et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001;98:6917–6922.

    PubMed  CAS  Google Scholar 

  92. Paterlini M, Zakharenko SS, Lai WS, et al. Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci 2005;8:1586–1594.

    PubMed  CAS  Google Scholar 

  93. Galderisi S, Maj M, Kirkpatrick B, et al. COMT Val(158)Met and BDNF C(270)T polymorphisms in schizophrenia: a case-control study. Schizophr Res 2005;73:27–30.

    PubMed  Google Scholar 

  94. Bilder RM, Volavka J, Czobor P, et al. Neurocognitive correlates of the COMT Val(158)Met polymorphism in chronic schizophrenia. Biol Psychiatry 2002;52:701–707.

    PubMed  CAS  Google Scholar 

  95. Nolan KA, Bilder RM, Lachman HM, Volavka J. Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Va l and Met alleles on cognitive stability and flexibility. Am J Psychiatry 2004;161:359–361.

    PubMed  Google Scholar 

  96. Franke P, Maier W, Hain C, Klingler T. Wisconsin Card Sorting Test: an indicator of vulnerability to schizophrenia? Schizophr Res 1992;6:243–249.

    PubMed  CAS  Google Scholar 

  97. Goldberg TE, Egan MF, Gscheidle T, et al. Executive sub-processes in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 2003;60:889–896.

    PubMed  CAS  Google Scholar 

  98. Ho BC, Wassink TH, O'Leary DS, Sheffield VC, Andreasen NC. Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow. Mol Psychiatry 2005;10:229, 287–298.

    CAS  Google Scholar 

  99. Weickert TW, Goldberg TE, Mishara A, et al. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol Psychiatry 2004;56:677–682.

    PubMed  CAS  Google Scholar 

  100. Baldeweg T, Klugman A, Gruzelier J, Hirsch SR. Mismatch negativity potentials and cognitive impairment in schizophrenia. Schizophr Res 2004;69:203–217.

    PubMed  Google Scholar 

  101. Umbricht D, Krljes S. Mismatch negativity in schizophrenia: a meta-analysis. Schizophr Res 2005;76:1–23.

    PubMed  Google Scholar 

  102. Todd J, Michie PT, Budd TW, Rock D, Jablensky AV. Auditory sensory memory in schizophrenia: inadequate trace formation? Psychiatry Res 2000;96:99–115.

    PubMed  CAS  Google Scholar 

  103. Michie PT, Innes-Brown H, Todd J, Jablensky AV. Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders. Biol Psychiatry 2002;52:749–758.

    PubMed  Google Scholar 

  104. Bramon E, Croft RJ, McDonald C, et al. Mismatch negativity in schizophrenia: a family study. Schizophr Res 2004;67:1–10.

    PubMed  Google Scholar 

  105. Baker K, Baldeweg T, Sivagnanasundaram S, Scambler P, Skuse D. COMT Val108/158 Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome. Biol Psychiatry 2005;58:23–31.

    PubMed  CAS  Google Scholar 

  106. Umbricht D, Koller R, Schmid L, et al. How specific are deficits in mismatch negativity generation to schizophrenia? Biol Psychiatry 2003;53:1120–1131.

    PubMed  Google Scholar 

  107. Baldeweg T, Wong D, Stephan KE. Nicotinic modulation of human auditory sensory memory: Evidence from mismatch negativity potentials. Int J Psychophysiol 2006;59:49–58.

    PubMed  Google Scholar 

  108. Oknina LB, Wild-Wall N, Oades RD, et al. Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset. Schizophr Res 2005;76:25–41.

    PubMed  CAS  Google Scholar 

  109. Magno E, Yeap S, Thakore JH, Garavan H, De Sanctis P, Foxe JJ. Are auditory-evoked frequency and duration mismatch negativity deficits endophenotypic for schizophrenia? High-density electrical mapping in clinically unaffected first-degree relatives and first-episode and chronic schizophrenia. Biol Psychiatry, 2008;64(5):385–391.

    Google Scholar 

  110. Tost H, Meyer-Lindenberg A, Ruf M, et al. [One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging]. Radiologe 2005;45:113–118, 120–113.

    PubMed  CAS  Google Scholar 

  111. 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  Google Scholar 

  112. Strafella AP, Paus T, Fraraccio M, Dagher A. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 2003;126:2609–2615.

    PubMed  Google Scholar 

  113. Zangen A, Hyodo K. Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens. Neuroreport 2002;13:2401–2405.

    PubMed  CAS  Google Scholar 

  114. Venables NC, Bernat EM, Sponheim SR. Genetic and dis-order-specific aspects of resting state EEG abnormalities in schizophrenia. Schizophr Bull, 2008; [Epub ahead of print]

    Google Scholar 

  115. Weisbrod M, Hill H, Sauer H, et al. Nongenetic pathologic developments of brain-wave patterns in monozygotic twins discordant and concordant for schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2004;125B:1–9.

    PubMed  CAS  Google Scholar 

  116. Hans SL, Auerbach JG, Auerbach AG, Marcus J. Development from birth to adolescence of children at-risk for schizophrenia. J Child Adolesc Psychopharmacol 2005;15:384–394.

    PubMed  Google Scholar 

  117. Erlenmeyer-Kimling L, Rock D, Roberts SA, et al. Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. Am J Psychiatry 2000;157:1416–1422.

    PubMed  CAS  Google Scholar 

  118. Erlenmeyer-Kimling L. Neurobehavioral deficits in offspring of schizophrenic parents: liability indicators and predictors of illness. Am J Med Genet 2000;97:65–71.

    PubMed  CAS  Google Scholar 

  119. Galderisi S, Maj M, Kirkpatrick B, et al. Catechol-O-methyltransferase Val158Met polymorphism in schizophrenia: associations with cognitive and motor impairment. Neuropsychobiology 2005;52:83–89.

    PubMed  CAS  Google Scholar 

  120. Westphal KP. The Bereitschaftspotential in schizophrenia and depression. In Jahanshahi M, Hallett M, eds. The Bereitschaftspotential - movement-related cortical potentials. New York: Kluwer/Plenum; 2003:155–174.

    Google Scholar 

  121. Karaman T, Ozkaynak S, Yaltkaya K, Buyukberker C. Bereitschaftpotential in schizophrenia. Br J Psychiatry 1997;171:31–34.

    PubMed  CAS  Google Scholar 

  122. Dreher JC, Trapp W, Banquet JP, Keil M, Gunther W, Burnod Y. Planning dysfunction in schizophrenia: impairment of potentials preceding fixed/free and single/sequence of self-initiated finger movements. Exp Brain Res 1999;124:200–214.

    PubMed  CAS  Google Scholar 

  123. Kubota F, Miyata H, Shibata N, Yarita H. A study of motor dysfunction associated with schizophrenia based on analyses of movement-related cerebral potentials and motor conduction time. Biol Psychiatry 1999;45:412–416.

    PubMed  CAS  Google Scholar 

  124. Northoff G, Pfennig A, Krug M, et al. Delayed onset of late movement-related cortical potentials and abnormal response to lorazepam in catatonia. Schizophr Res 2000;44:193–211.

    PubMed  CAS  Google Scholar 

  125. Adler LE, Pecevich M, Nagamoto H. Bereitschaftspotential in tardive dyskinesia. Mov Disord 1989;4:105–112.

    PubMed  CAS  Google Scholar 

  126. Tecce JJ. Dopamine and CNV: studies of drugs, disease and nutrition. Electroencephalogr Clin Neurophysiol Suppl 1991;42:153–164.

    PubMed  CAS  Google Scholar 

  127. Tecce JJ, Gardos G, Cole JO, Bowers PA. A CNV typology of chronic schizophrenics and response to drug treatment. Psychopharmacol Bull 1979;15:39–41.

    PubMed  CAS  Google Scholar 

  128. Timsit-Berthier M, Delaunoy J, Koninckx N, Rousseau JC. Slow potential changes in psychiatry. I. Contingent negative variation. Electroencephalogr Clin Neurophysiol 1973;35:355–361.

    CAS  Google Scholar 

  129. Wagner M, Rendtorff N, Kathmann N, Engel RR. CNV, PINV and probe-evoked potentials in schizophrenics. Electroencephalogr Clin Neurophysiol 1996;98:130–143.

    PubMed  CAS  Google Scholar 

  130. Chiarenza GA, Papakostopoulos D, Dini M, Cazzullo CL. Neurophysiological correlates of psychomotor activity in chronic schizophrenics. Electroencephalogr Clin Neurophysiol 1985;61:218–228.

    PubMed  CAS  Google Scholar 

  131. Singh J, Knight RT, Rosenlicht N, Kotun JM, Beckley DJ, Woods DL. Abnormal premovement brain potentials in schizophrenia. Schizophr Res 1992;8:31–41.

    PubMed  CAS  Google Scholar 

  132. Fuller R, Nathaniel-James D, Jahanshahi M. Movement-related potentials prior to self-initiated movements are impaired in patients with schizophrenia and negative signs. Exp Brain Res 1999;126:545–555.

    PubMed  CAS  Google Scholar 

  133. Fuller R, Jahanshahi M. Impairment of willed actions and use of advance information for movement preparation in schizophrenia. J Neurol Neurosurg Psychiatry 1999;66:502–509.

    PubMed  CAS  Google Scholar 

  134. Fuller R, Jahanshahi M. Concurrent performance of motor tasks and processing capacity in patients with schizophrenia. J Neurol Neurosurg Psychiatry 1999;66:668–671.

    PubMed  CAS  Google Scholar 

  135. van den Bosch RJ, Rozendaal N. Subjective cognitive dysfunction, eye tracking, and slow brain potentials in schizophrenic and schizoaffective patients. Biol Psychiatry 1988;24:741–746.

    PubMed  Google Scholar 

  136. Verleger R, Wascher E, Arolt V, Daase C, Strohm A, Kompf D. Slow EEG potentials (contingent negative variation and post-imperative negative variation) in schizophrenia: their association to the present state and to Parkinsonian medication effects. Clin Neurophysiol 1999;110:1175–1192.

    PubMed  CAS  Google Scholar 

  137. Klein C, Rockstroh B, Cohen R, Berg P. Contingent negative variation (CNV) and determinants of the post-imperative negative variation (PINV) in schizophrenic patients and healthy controls. Schizophr Res 1996;21:97–110.

    PubMed  CAS  Google Scholar 

  138. Klein C, Andresen B, Berg P, Kruger H, Rockstroh B. Topography of CNV and PINV in schizotypal personality. Psychophysiology 1998;35:272–282.

    PubMed  CAS  Google Scholar 

  139. Kathmann N, Jonitz L, Engel RR. Cognitive determinants of the postimperative negative variation. Psychophysiology 1990;27:256–263.

    PubMed  CAS  Google Scholar 

  140. Rockstroh B, Cohen R, Berg P, Klein C. The postimpera-tive negative variation following ambiguous matching of auditory stimuli. Int J Psychophysiol 1997;25:155–167.

    PubMed  CAS  Google Scholar 

  141. Rockstroh B, Cohen R, Hauk O, et al. Topography of the post-imperative negative variation in schizophrenic patients and controls obtained from high-resolution ERP maps. Electroencephalogr Clin Neurophysiol Suppl 1999;49: 210–214.

    Google Scholar 

  142. Strandburg RJ, Marsh JT, Brown WS, Asarnow RF, Guthrie D. Information-processing deficits across childhood- and adult-onset schizophrenia. Schizophr Bull 1994;20: 685–695.

    PubMed  CAS  Google Scholar 

  143. Yee BK, Keist R, von Boehmer L, et al. A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction. Proc Natl Acad Sci U S A 2005;102:17154–17159.

    PubMed  CAS  Google Scholar 

  144. Westphal KP, Grozinger B, Becker W, et al. Spectral analysis of EEG during self-paced movements: differences between untreated schizophrenics and normal controls. Biol Psychiatry 1992;31:1020–1037.

    PubMed  CAS  Google Scholar 

  145. Mattay VS, Callicott JH, Bertolino A, et al. Abnormal functional lateralization of the sensorimotor cortex in patients with schizophrenia. Neuroreport 1997;8:2977–2984.

    PubMed  CAS  Google Scholar 

  146. Schroder J, Wenz F, Schad LR, Baudenstiel K, Knopp MV. Sensorimotor cortex and supplementary motor area changes in schizophrenia. A study with functional magnetic resonance imaging. Br J Psychiatry 1995;167:197–201.

    CAS  Google Scholar 

  147. Schroder J, Essig M, Baudenstiel K, et al. Motor dysfunction and sensorimotor cortex activation changes in schizophrenia: A study with functional magnetic resonance imaging. Neuroimage 1999;9:81–87.

    PubMed  CAS  Google Scholar 

  148. Bertolino A, Blasi G, Caforio G, et al. Functional lateral-ization of the sensorimotor cortex in patients with schizophrenia: effects of treatment with olanzapine. Biol Psychiatry 2004;56:190–197.

    PubMed  CAS  Google Scholar 

  149. Erlenmeyer-Kimling L, Hans S, Ingraham L, et al. Handedness in children of schizophrenic parents: data from three high-risk studies. Behav Genet 2005;35:351–358.

    PubMed  CAS  Google Scholar 

  150. Johnstone EC, Ebmeier KP, Miller P, Owens DG, Lawrie SM. Predicting schizophrenia: findings from the Edinburgh High-Risk Study. Br J Psychiatry 2005;186:18–25.

    PubMed  Google Scholar 

  151. Leask SJ, Done DJ, Crow TJ. Adult psychosis, common childhood infections and neurological soft signs in a national birth cohort. Br J Psychiatry 2002;181:387–392.

    PubMed  CAS  Google Scholar 

  152. Obiols JE, Serrano F, Caparros B, Subira S, Barrantes N. Neurological soft signs in adolescents with poor performance on the continous performance test: markers of liability for schizophrenia spectrum disorders? Psychiatry Res 1999;86:217–228.

    PubMed  CAS  Google Scholar 

  153. Niethammer R, Weisbrod M, Schiesser S, et al. Genetic influ-ence on laterality in schizophrenia? A twin study of neurological soft signs. Am J Psychiatry 2000;157:272–274.

    PubMed  CAS  Google Scholar 

  154. Hans SL, Marcus J, Nuechterlein KH, Asarnow RF, Styr B, Auerbach JG. Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study. Arch Gen Psychiatry 1999;56:741–748.

    PubMed  CAS  Google Scholar 

  155. Browne S, Clarke M, Gervin M, et al. Determinants of neurological dysfunction in first episode schizophrenia. Psychol Med 2000;30:1433–1441.

    PubMed  CAS  Google Scholar 

  156. Bottmer C, Bachmann S, Pantel J, et al. Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia. Psychiatry Res 2005;140:239–250.

    PubMed  Google Scholar 

  157. Lu B Y, Martin KE, Edgar JC, et al. Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia. Biol Psychiatry 2007;62:822–825.

    PubMed  CAS  Google Scholar 

  158. Freedman R, Olincy A, Ross RG, et al. The genetics of sensory gating deficits in schizophrenia. Curr Psychiatry Rep 2003;5:155–161.

    PubMed  Google Scholar 

  159. Leonard S, Adams C, Breese CR, et al. Nicotinic receptor function in schizophrenia. Schizophr Bull 1996;22:431–445.

    PubMed  CAS  Google Scholar 

  160. Cadenhead KS, Light GA, Shafer KM, Braff DL. P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment. Biol Psychiatry 2005;57:1504–1509.

    PubMed  Google Scholar 

  161. Light GA, Braff DL. The “incredible shrinking” P50 event-related potential. Biol Psychiatry 1998;43:918–920.

    PubMed  CAS  Google Scholar 

  162. Light GA, Geyer MA, Clementz BA, Cadenhead KS, Braff DL. Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Am J Psychiatry 2000;157:767–771.

    PubMed  CAS  Google Scholar 

  163. Myles-Worsley M. P50 sensory gating in multiplex schizophrenia families from a Pacific island isolate. Am J Psychiatry 2002;159:2007–2012.

    PubMed  Google Scholar 

  164. Myles-Worsley M, Ord L, Blailes F, Ngiralmau H, Freedman R. P50 sensory gating in adolescents from a pacific island isolate with elevated risk for schizophrenia. Biol Psychiatry 2004;55:663–667.

    PubMed  Google Scholar 

  165. Winterer G, Egan MF, Radler T, Coppola R, Weinberger DR. Event-related potentials and genetic risk for schizophrenia. Biol Psychiatry 2001;50:407–417.

    PubMed  CAS  Google Scholar 

  166. Schulze KK, Hall MH, McDonald C, et al. P50 auditory evoked potential suppression in bipolar disorder patients with psychotic features and their unaffected relatives. Biol Psychiatry 2007;62:121–128.

    PubMed  Google Scholar 

  167. Weisser R, Weisbrod M, Roehrig M, Rupp A, Schroeder J, Scherg M. Is frontal lobe involved in the generation of auditory evoked P50? Neuroreport 2001;12:3303–3307.

    PubMed  CAS  Google Scholar 

  168. Kisley MA, Polk SD, Ross RG, Levisohn PM, Freedman R. Early postnatal development of sensory gating. Neuroreport 2003;14:693–697.

    PubMed  Google Scholar 

  169. Marshall PJ, Bar-Haim Y, Fox NA. The development of P50 suppression in the auditory event-related potential. Int J Psychophysiol 2004;51:135–141.

    PubMed  Google Scholar 

  170. de Wilde OM, Bour LJ, Dingemans PM, Koelman JH, Linszen DH. A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups. Schizophr Res 2007;97: 137–151.

    PubMed  Google Scholar 

  171. Anokhin AP, Vedeniapin AB, Heath AC, Korzyukov O, Boutros NN. Genetic and environmental influences on sensory gating of mid-latency auditory evoked responses: a twin study. Schizophr Res 2007;89:312–319.

    PubMed  Google Scholar 

  172. Cadenhead KS, Light GA, Geyer MA, McDowell JE, Braff DL. Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? Am J Psychiatry 2002;159:869–871.

    PubMed  Google Scholar 

  173. Gottesman, II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636–645.

    PubMed  Google Scholar 

  174. Arnold SE, Talbot K, Hahn CG. Neurodevelopment, neu-roplasticity, and new genes for schizophrenia. Prog Brain Res 2005;147:319–345.

    PubMed  CAS  Google Scholar 

  175. Hashimoto R, Straub RE, Weickert CS, et al. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry 2004;9:299–307.

    PubMed  CAS  Google Scholar 

  176. Weickert CS, Hyde TM, Lipska BK, et al. Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2003;8:592–610.

    PubMed  CAS  Google Scholar 

  177. Gogtay N, Sporn A, Clasen LS, et al. Comparison of progressive cortical gray matter loss in childhood-onset schizophrenia with that in childhood-onset atypical psychoses. Arch Gen Psychiatry 2004;61:17–22.

    PubMed  Google Scholar 

  178. Gogtay N, Sporn A, Clasen LS, et al. Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia. Am J Psychiatry 2003;160:569–571.

    PubMed  Google Scholar 

  179. Gogtay N, Giedd J, Rapoport JL. Brain development in healthy, hyperactive, and psychotic children. Arch Neurol 2002;59:1244–1248.

    PubMed  Google Scholar 

  180. Pantelis C, Velakoulis D, McGorry PD, et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003;361:281–288.

    PubMed  Google Scholar 

  181. Pantelis C, Yucel M, Wood SJ, et al. Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophr Bull 2005;31:672–696.

    PubMed  Google Scholar 

  182. Sporn AL, Greenstein DK, Gogtay N, et al. Progressive brain volume loss during adolescence in childhood-onset schizophrenia. Am J Psychiatry 2003;160:2181–2189.

    PubMed  Google Scholar 

  183. Thompson PM, Vidal C, Giedd JN, et al. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A 2001;98:11650–11655.

    PubMed  CAS  Google Scholar 

  184. Gogtay N, Giedd JN, Lusk L, et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A 2004;101:8174–8179.

    PubMed  CAS  Google Scholar 

  185. Cannon TD, van Erp TG, Huttunen M, et al. Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry 1998;55:1084–1091.

    PubMed  CAS  Google Scholar 

  186. McDonald C, Grech A, Toulopoulou T, et al. Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives. Am J Med Genet 2002;114:616–625.

    PubMed  Google Scholar 

  187. Cannon TD, van Erp TG, Bearden CE, et al. Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophr Bull 2003;29:653–669.

    PubMed  Google Scholar 

  188. Buchsbaum MS, Friedman J, Buchsbaum BR, et al. Diffusion tensor imaging in schizophrenia. Biol Psychiatry 2006;60:1181–1187.

    PubMed  Google Scholar 

  189. Winterer G, Coppola R, Goldberg TE, et al. Prefrontal broadband noise, working memory, and genetic risk for schizophrenia. Am J Psychiatry 2004;161:490–500.

    PubMed  Google Scholar 

  190. Winterer G, Weinberger DR. Genes, dopamine and cortical signal-to-noise ration in schizophrenia. Trends Neurosci 2004;27:683–690.

    PubMed  CAS  Google Scholar 

  191. Weinberger DR, Lipska BK. Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophr Res 1995;16:87–110.

    PubMed  CAS  Google Scholar 

  192. Yoon JH, Minzenberg MJ, Ursu S, Walters R, Wendelken C, Ragland JD, Carter CS Association of dorsolateral pre-frontal cortex dysfunction with disrupted coordinated brain activity in schizophrenia: relationship with impaired cognition, behavioral disorganization, and global function. Am J Psychiatry, 2008;165(8):1006–1014.

    PubMed  Google Scholar 

  193. Spencer KM, Nestor PG, Perlmutter R, et al. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc Natl Acad Sci U S A 2004;101:17288–17293.

    PubMed  CAS  Google Scholar 

  194. Winterer G, Coppola R, Egan MF, Goldberg TE, Weinberger DR. Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. Biol Psychiatry 2003;54:1181–1192.

    PubMed  Google Scholar 

  195. Bender S, Weisbrod M, Bornfleth H, Resch F, Oelkers-Ax R. How do children prepare to react? Imaging maturation of motor preparation and stimulus anticipation by late contingent negative variation. Neuroimage 2005;27:737–752.

    PubMed  Google Scholar 

  196. Fish B, Kendler KS. Abnormal infant neurodevelopment predicts schizophrenia spectrum disorders. J Child Adolesc Psychopharmacol 2005;15:348–361.

    PubMed  Google Scholar 

  197. Weaver IC, Cervoni N, Champagne FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004;7:847–854.

    PubMed  CAS  Google Scholar 

  198. Kato T, Iwamoto K, Kakiuchi C, Kuratomi G, Okazaki Y. Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders. Mol Psychiatry 2005;10:622–630.

    PubMed  CAS  Google Scholar 

  199. Caruncho HJ, Dopeso-Reyes IG, Loza MI, Rodriguez MA. A GABA, reelin, and the neurodevelopmental hypothesis of schizophrenia. Crit Rev Neurobiol. 2004;16:25–32.

    PubMed  CAS  Google Scholar 

  200. Riley B. Linkage studies of schizophrenia. Neurotox Res 2004;6:17–34.

    PubMed  Google Scholar 

  201. Lewis CM, Levinson DF, Wise LH, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 2003;73:34–48.

    PubMed  CAS  Google Scholar 

  202. Iwata Y, Nakajima M, Yamada K, et al. Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia. Neurosci Res 2007;57: 194–202.

    Google Scholar 

  203. Puri V, McQuillin A, Thirumalai S, 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.

    PubMed  CAS  Google Scholar 

  204. Fallin MD, Lasseter VK, Wolyniec PS, 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.

    Google Scholar 

  205. Abou Jamra R, Schmael C, Cichon S, Rietschel M, Schumacher J, Nothen MM. The G72/G30 gene locus in psychiatric disorders: a challenge to diagnostic boundaries? Schizophr Bull 2006;32:599–608.

    PubMed  Google Scholar 

  206. Schulze KK, Hall MH, McDonald C, et al. P50 Auditory Evoked Potential Suppression in Bipolar Disorder Patients With Psychotic Features and Their Unaffected Relatives. Biol Psychiatry 2007;62:121–128.

    PubMed  Google Scholar 

  207. Bramon E, Dempster E, Frangou S, et al. Is there an association between the COMT gene and P300 endopheno-types? Eur Psychiatry 2006;21:70–73.

    PubMed  CAS  Google Scholar 

  208. Jin Y, Bunney WE, Jr., Sandman CA, et al. Is P50 suppression a measure of sensory gating in schizophrenia? Biol Psychiatry 1998;43:873–878.

    PubMed  CAS  Google Scholar 

  209. de Wilde O, Bour L, Dingemans P, Koelman J, Linszen D. Failure to find P50 suppression deficits in young first-epi-sode patients with schizophrenia and clinically unaffected siblings. Schizophr Bull 2007;97:137–151.

    Google Scholar 

  210. Arnfred SM, Chen AC, Glenthoj BY, Hemmingsen RP. Normal p50 gating in unmedicated schizophrenia outpatients. Am J Psychiatry 2003;160:2236–2238.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bender, S., Weisbrod, M., Resch, F. (2009). Functional and Structural Endophenotypes in Schizophrenia. In: Ritsner, M.S. (eds) The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9831-4_4

Download citation

Publish with us

Policies and ethics