RSS-Feed abonnieren
DOI: 10.1055/s-0038-1627802
Schizophrenia as a network disorder
From a dysfunction of neuronal networks to a dysfunction of gene nets Artikel in mehreren Sprachen: deutsch | EnglishPublikationsverlauf
Eingegangen am:
02. September 2010
angenommen am:
24. September 2010
Publikationsdatum:
23. Januar 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00034916/201104/lookinside/thumbnails/10-1055-s-0038-1627802_en-1.jpg)
Summary
Schizophrenia is a severe mental disorder with an unfavourable outcome for more than 50% of the sufferers. Looking at its pathophysiology, it recently became more and more evident that it is not a classical neurodegenerative disease, but a disorder with dysfunctional regenerative processes of the human brain. Its etiology shows an interaction of environmental and genetic factors as can be seen in complex disorders. Meanwhile we learned that beside the „copy number variations” (CNVs) and risk genes (e. g. NRG-1, G72), also epigenetic mechanisms play a pivotal role for the significant influence of environmental factors on the pathophysiology. Understanding certain pathophysiological aspects of the clinical symptomatology like cognitive dysfunction should promote the development of add-on therapies improving the long-term outcome of schizophrenia.
-
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.
- 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.
- 3 Bayer TA. et al. Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett 1999; 271: 126-128.
- 4 Bogerts B, Falkai P, Greve B. Evidence of reduced temporolimbic structure volumes in schizophrenia. Arch Gen Psychiatry 1991; 48: 956-958.
- 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.
- 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.
- 7 Davidson M. et al. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 1999; 156: 1328-1335.
- 8 Davies N, Russell A, Jones P, Murray RM. Which characteristics of schizophrenia predate psychosis?. J Psychiatr Res 1998; 32: 121-131.
- 9 Duan J, Sanders AR, Gejman PV. Genome-wide approaches to schizophrenia. Brain Res Bull. 2010 Apr 28, Epub ahead of print.
- 10 Ebner F. et al. The hippocampus in families with schizophrenia in relation to obstetric complications. Schizophr Res 2008; 104: 71-78.
- 11 Esslinger C. et al. Neural mechanisms of a genomewide supported psychosis variant. Science 2009; 324: 605.
- 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.
- 13 Freedman R. et al. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 2008; 65: 1040-7.
- 14 Häfner H, an der Heiden W. Course and outcome of schizophrenia. In: Hirsch S, Weinberger D. (Eds.), Schizophrenia. Berlin: Blackwell; 2003
- 15 Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005; 10: 40-68.
- 16 Hasan A, Falkai P, Wobrock T. Early detection and treatment of schizophrenia. MMW Fortschr Med 2010; 152: 53-55.
- 17 Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998; 12: 426-445.
- 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.
- 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.
- 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.
- 21 Hoff AL. et al. Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia. Am J Psychiatry 1999; 156: 1336-1341.
- 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.
- 23 Honer WG. et al. Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. Cereb Cortex 2002; 12: 349-356.
- 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.
- 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.
- 26 Lieberman JA. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209-1223.
- 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.
- 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.
- 29 Merikangas AK, Corvin AP, Gallagher L. Copynumber variants in neurodevelopmental disorders: promises and challenges. Trends Genet 2009; 25: 536-544.
- 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.
- 31 Pajonk FG. et al. Hippocampal plasticity in response to exercise in schizophrenia. Arch Gen Psychiatry 2010; 67: 133-143.
- 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.
- 33 Sananbenesi F, Fischer A. The epigenetic bottleneck of neurodegenerative and psychiatric diseases. Biol Chem 2009; 390: 1145-1153.
- 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.
- 35 Schmitt A. et al. Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathologica 2009; 117: 395-407.
- 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.
- 37 Stefansson H. et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877-892.
- 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.