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Pharmacopsychiatry 2006; 39: 68-71
DOI: 10.1055/s-2006-931498
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Cortical Microcircuits in Schizophrenia - The Dopamine Hypothesis Revisited

G. Winterer1
  • 1Department of Psychiatry, Heinrich-Heine University Hospital Duesseldorf, Germany
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Publication History

Publication Date:
01 March 2006 (online)

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Strong evidence exists for disturbed functional connectivity of cortical microcircuits - particularly of prefrontal cortex. Dopamine, long implicated in antipsychotic drug effects, is crucially involved in optimizing signal-to-noise ratio of local cortical micro-circuits. This action of dopamine is achieved by means of D1- and D2-receptor-mediated effects on pyramidal and local circuit neurons, which mediate recurrent inhibition and thus contribute to the stability of cortical representations of external and internal stimuli. In schizophrenia, a diminished cortical dopamine D1/D2 activation ratio - in concert with altered GABAergic and glutamatergic transmission - appear to critically interfere with this process.

References

  • 1 Carlsson A. Historical aspects and future directions. In: Kapur S, Lecrubier Y, eds Dopamine in the pathophysiology and treatment of schizophrenia. Martin Dunitz London; 2003: 1-14
    Search in Google Scholar
  • 2 Winterer G, Weinberger D R. Schizophrenia: Genes, dopamine and cortical signal-to-noise ratio in schizophrenia.  Trends in Neurosci. 2004;  27 683-690
    CrossrefPubMedSearch in Google Scholar
  • 3 Winterer G, Ziller M, Dorn H, Frick K, Wuebben Y, Mulert C, Herrmann W M, Coppola R. Schizophrenia: Reduced signal-to-noise ratio and impaired phase-locking during information processing.  Clin Neurophysiol. 2000;  111 837-849
    CrossrefPubMedSearch in Google Scholar
  • 4 Winterer G, Coppola R, Goldberg T E, Egan M F, Jones D W, Sanchez C E, Weinberger D R. Prefrontal broadband noise, working memory & genetic risk for schizophrenia.  Am J Psychiat. 2004;  161 1-11
    PubMedSearch in Google Scholar
  • 5 Winterer G, Musso F, Beckmann C, Mattay V, Egan M F, Jones D W, Callicott J H, Coppola R, Weinberger D R. Instability of prefrontal BOLD-response in schizophrenia. Am J Psychiat (in press)
  • 6 Winterer G, Egan M F, Kolachana B S, Goldberg T E, Coppola R, Weinberger D R. Prefrontal noise and COMT genotype pattern in schizophrenia. Biol Psychiatry (in press)
  • 7 Durstewitz D, Seamans J K, Sejnowski T J. Neurocomputational models of working memory.  Nat Neurosci. 2000;  3 Suppl 1184-1191
    CrossrefPubMedSearch in Google Scholar
  • 8 Durstewitz D, Seamans J K. The computational role of dopamine D1 receptors in working memory.  Neural Netw. 2002;  15 561-572
    CrossrefPubMedSearch in Google Scholar
  • 9 Williams G V, Goldman-Rakic P S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex.  Nature. 1995;  376 572-575
    CrossrefPubMedSearch in Google Scholar
  • 10 Peters Y, Barnhardt N E, O'Donnell P. Prefrontal cortical up states are synchronized with ventral tegmental area activity.  Synapse. 2004;  52 143-152
    CrossrefPubMedSearch in Google Scholar
  • 11 Seamans J K, Durstewitz D, Christie B R, Stevens C F, Sejnowski T J. Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons.  Proc Natl Acad Sci USA. 2001;  98 301-306
    CrossrefPubMedSearch in Google Scholar
  • 12 Wang J, O'Donnell P. D(1) dopamine receptors potentiate NMDA-mediated excitability increase in layer V prefrontal cortical pyramidal neurons.  Cereb Cortex. 2001;  11 452-462
    CrossrefPubMedSearch in Google Scholar
  • 13 Seamans J K, Gorelova N, Durstewitz D, Yang C R. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons.  J Neurosci. 2001;  21 3628-3638
    PubMedSearch in Google Scholar
  • 14 Meltzer H. Multiple neurotransmitters involved in antipsychotic action. In: Kapur S & Lecrubier Y, eds Dopamine in the Pathophysiology and Treatment of Schizophrenia. Martin Dunitz London; 2003: 177-206
    Search in Google Scholar
  • 15 Keefe R S, Young C A, Rock S L, Purdon S E, Gold J M, Breier A. One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia. Schizophr Res 2005; Sep 30 [Epub ahead of print]
    Search in Google Scholar
  • 16 Bertolino A, Caforio G, Blasi G, De Candia M, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott J H, Mattay V S, Bellomo A, Scarabino T, Weinberger D R, Nardini M. Interaction of COMT Val108/158 Met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.  Am J Psychiatry. 2004;  161 1798-1805
    CrossrefPubMedSearch in Google Scholar
  • 17 Daniel D G, Weinberger D R, Jones D W, Zigun J R, Coppola R, Handel S, Bigelow L B, Goldberg T E, Berman K F, Kleinman J E. The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.  J Neurosci. 1991;  11 1907-1917
    PubMedSearch in Google Scholar
  • 18 Anderer P, Saletu B, Semlitsch H, Pascual-Marqui R D. Perceptual and cognitive event-related potentials in neuropsychopharmacology: methodological aspects and clinical applications (pharmaco-ERP topography and tomography).  Methods Find Exp Clin Pharmacol. 2002;  24 (Suppl. C) 121-137
    PubMedSearch in Google Scholar

Georg Winterer, MD, PhD

Dept. of Psychiatry

Heinrich-Heine University Hospital

Bergische Landstr. 2

D-40629 Duesseldorf

Germany

Phone: +49-(0)211-922-3463

Fax: +49-(0)211-922-3498

Email: georg.winterer@uni-duesseldorf.de