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Nervenheilkunde 2011; 30(04): 218-223
DOI: 10.1055/s-0038-1627802
Schizophrenie
Schattauer GmbH

Schizophrenie als Netzwerkstörung

Von einer Dysfunktion neuronaler Verbünde zu einer Dysregulation von Gennetzen Article in several languages: deutsch | English
P. Falkai
1   Abteilung für Psychiatrie und Psychotherapie, Zentrum Psychosoziale Medizin, Georg-August-Universität Göttingen
,
O. Gruber
1   Abteilung für Psychiatrie und Psychotherapie, Zentrum Psychosoziale Medizin, Georg-August-Universität Göttingen
,
T. G. Schulze
1   Abteilung für Psychiatrie und Psychotherapie, Zentrum Psychosoziale Medizin, Georg-August-Universität Göttingen
,
A. Schmitt
1   Abteilung für Psychiatrie und Psychotherapie, Zentrum Psychosoziale Medizin, Georg-August-Universität Göttingen
› Author Affiliations
Further Information

Publication History

Eingegangen am: 02 September 2010

angenommen am: 24 September 2010

Publication Date:
23 January 2018 (online)

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Zusammenfassung

Die Schizophrenie stellt eine schwere psychische Erkrankung dar, welche für mehr als 50% der Betroffenen einen ungünstigen Verlauf aufweist. Bei Betrachtung der Pathophysiologie hat sich in letzter Zeit in wachsendem Maße gezeigt, dass es sich nicht um eine klassische neurodegenerative Erkrankung, sondern um eine Störung mit einem dysfunktionalen regenerativen Prozess im menschlichen Gehirn handelt. Wie bei allen komplexen Erkrankungen zeigt sich auch in der Ätiologie der Schizophrenie eine Interaktion von genetischen und Umweltfaktoren. Wir wissen inzwischen, dass neben den „Copy Number Variations” (CNVs) und Risikogenen (z. B. NRG-1, G72) auch epigenetische Mechanismen für den signifikanten Einfluss von Umweltfaktoren auf die Pathophysiologie von zentraler Bedeutung sind. Das Verständnis bestimmter pathophysiologischer Aspekte der klinischen Symptomatik wie der kognitiven Dysfunktion, dürfte zur Entwicklung zusätzlicher Therapien beitragen, welche den longitudinalen Verlauf der Schizophrenie verbessern.

Schlüsselwörter

Schizophrenie - Pathogenese - Hippocampus - Genetik - Langzeitverlauf
 

  • Literatur

  • 1 Albus M. et al. Neurocognitive functioning in patients with first-episode schizophrenia: results of a prospective 5-year follow-up study. Eur Arch Psychiatry Clin Neurosci 2006; 256: 442-451.
    CrossrefPubMedGoogle Scholar
  • 2 Amminger GP. et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 2010; 67: 146-154.
    CrossrefPubMedGoogle Scholar
  • 3 Bayer TA. et al. Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett 1999; 271: 126-128.
    CrossrefPubMedGoogle Scholar
  • 4 Bogerts B, Falkai P, Greve B. Evidence of reduced temporolimbic structure volumes in schizophrenia. Arch Gen Psychiatry 1991; 48: 956-958.
    CrossrefPubMedGoogle Scholar
  • 5 Cahn W. et al. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry 2002; 59: 1002-1010.
    CrossrefPubMedGoogle Scholar
  • 6 Cirillo MA, Seidman LJ. Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychol Rev 2003; 13: 43-77.
    CrossrefPubMedGoogle Scholar
  • 7 Davidson M. et al. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 1999; 156: 1328-1335.
    PubMedGoogle Scholar
  • 8 Davies N, Russell A, Jones P, Murray RM. Which characteristics of schizophrenia predate psychosis?. J Psychiatr Res 1998; 32: 121-131.
    CrossrefPubMedGoogle Scholar
  • 9 Duan J, Sanders AR, Gejman PV. Genome-wide approaches to schizophrenia. Brain Res Bull. 2010 Apr 28, Epub ahead of print.
    PubMedGoogle Scholar
  • 10 Ebner F. et al. The hippocampus in families with schizophrenia in relation to obstetric complications. Schizophr Res 2008; 104: 71-78.
    CrossrefPubMedGoogle Scholar
  • 11 Esslinger C. et al. Neural mechanisms of a genomewide supported psychosis variant. Science 2009; 324: 605.
    CrossrefPubMedGoogle Scholar
  • 12 Falkai P. et al. No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study. Neuropathol Appl Neurobiol 1999; 25: 48-53.
    CrossrefPubMedGoogle Scholar
  • 13 Freedman R. et al. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 2008; 65: 1040-7.
    Google Scholar
  • 14 Häfner H, an der Heiden W. Course and outcome of schizophrenia. In: Hirsch S, Weinberger D. (Eds.), Schizophrenia. Berlin: Blackwell; 2003
    Google Scholar
  • 15 Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005; 10: 40-68.
    CrossrefPubMedGoogle Scholar
  • 16 Hasan A, Falkai P, Wobrock T. Early detection and treatment of schizophrenia. MMW Fortschr Med 2010; 152: 53-55.
    PubMedGoogle Scholar
  • 17 Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998; 12: 426-445.
    CrossrefPubMedGoogle Scholar
  • 18 Helmstaedter C, Hauff M, Elger CE. Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy. J Clin Exp Neuropsychol 1998; 20: 365-75.
    CrossrefPubMedGoogle Scholar
  • 19 Henseler I, Falkai P, Gruber O. A systematic fMRI investigation of the brain systems subserving different working memory components in schizophrenia. Eur J Neurosci 2009; 30: 693-702.
    CrossrefPubMedGoogle Scholar
  • 20 Henseler I, Falkai P, Gruber O. Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: relation to performance and clinical symptoms. J Psychiatr Res 2009; 44: 364-372.
    PubMedGoogle Scholar
  • 21 Hoff AL. et al. Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia. Am J Psychiatry 1999; 156: 1336-1341.
    PubMedGoogle Scholar
  • 22 Hoff AL. et al. Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia. Schizophr Res 2005; 78: 27-34.
    CrossrefPubMedGoogle Scholar
  • 23 Honer WG. et al. Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. Cereb Cortex 2002; 12: 349-356.
    CrossrefPubMedGoogle Scholar
  • 24 Hurlemann R. et al. Interrelated neuropsychological and anatomical evidence of hippocampal pathology in the at-risk mental state. Psychol Med 2008; 38: 843-851.
    PubMedGoogle Scholar
  • 25 Kahn RS. et al. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371: 1085-1097.
    CrossrefPubMedGoogle Scholar
  • 26 Lieberman JA. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209-1223.
    CrossrefPubMedGoogle Scholar
  • 27 Lubman AL. et al. Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia. Acta Psychiatr Scand 2002; 106: 331-336.
    CrossrefPubMedGoogle Scholar
  • 28 Meisenzahl EM. et al. Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation. Eur Arch Psychiatry Clin Neurosci 2006; 256: 522-531.
    CrossrefPubMedGoogle Scholar
  • 29 Merikangas AK, Corvin AP, Gallagher L. Copynumber variants in neurodevelopmental disorders: promises and challenges. Trends Genet 2009; 25: 536-544.
    CrossrefPubMedGoogle Scholar
  • 30 Nelson MD. et al. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry 1998; 55: 433-440.
    CrossrefPubMedGoogle Scholar
  • 31 Pajonk FG. et al. Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry 2010; 67: 133-143.
    CrossrefPubMedGoogle Scholar
  • 32 Reichenberg A. et al. A population-based cohort study of premorbid intellectual, language, and behavioral functioning in patients with schizophrenia, schizoaffective disorder, and nonpsychotic bipolar disorder. Am J Psychiatry 2002; 159: 2027-2035.
    CrossrefPubMedGoogle Scholar
  • 33 Sananbenesi F, Fischer A. The epigenetic bottleneck of neurodegenerative and psychiatric diseases. Biol Chem 2009; 390: 1145-1153.
    PubMedGoogle Scholar
  • 34 Schmitt A. et al. Hippocampal volume and cell proliferation after acute and chronic clozapine or haloperidol treatment. J Neural Transm 2004; 111: 91-100.
    CrossrefPubMedGoogle Scholar
  • 35 Schmitt A. et al. Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathologica 2009; 117: 395-407.
    CrossrefPubMedGoogle Scholar
  • 36 Schulze TG. Genetic research into bipolar disorder: the need for a research framework that integrates sophisticated molecular biology and clinically informed phenotype characterization. Psychiatr Clin North Am 2010; 33: 67-82.
    CrossrefPubMedGoogle Scholar
  • 37 Stefansson H. et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877-892.
    CrossrefPubMedGoogle Scholar
  • 38 van Haren NE. et al. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacol 2007; 32: 2057-2066.
    CrossrefPubMedGoogle Scholar