Prefrontal Dopamine Signaling in Schizophrenia - The Corticocentric Model

Abstract

Diminished prefrontal dopamine (DA) signaling apparently contributes to schizophrenia illness. In the proposed corticocentric model, diminished DA is changing the D2/D1 receptor activation ratio in favor of D2 activation which - through a cascade of intracellular molecular events - ultimately decreases the neuronal signal-to-noise ratio (SNR) thereby destabilizing cortical microcircuits resulting in cognitive deficits and other clinical symptoms. The present overview will outline cortical DA effects both on the neural network and systems biology level and their relationship to schizophrenia illness. The proposed model will be finally discussed within the framework of the currently still dominant hypothesis of the striatal hyperdopaminergic state in schizophrenia.

References

• 1 Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang DR, Keilp J, Kochan L, Heertum R Van, Gorman JM, Laruelle M. Prefrontal dopamine D1 receptors and working memory in schizophrenia.  J Neurosci. 2002;  22 3708-3719
• 2 Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR, Lewis DA. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects.  Am J Psychiatry. 1999;  56 1580-1589
• 3 Albert KA, Hemmings  Jr  HC, Adamo AI, Potkin SG, Akbarian S, Sandman CA, Cotman CW, Bunney  Jr  WE, Greengard P. Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia.  Arch Gen Psychiatry. 2002;  59 705-712
• 4 Arnsten AFT, Goldman-Rakic PS. Stress impairs prefrontal cortex cognitive function in monkeys: role of dopamine.  Soc Neurosci Abstr. 1990;  16 164
• 5 Arnsten AFT. The biology of feeling frazzled.  Science. 1998;  280 1711-1712
• 6 Arnsten AFT. Through the looking glass: differential noradrenergic modulation of prefrontal cortical function.  Neural Plast. 2000;  7 133-146
• 7 Arnsten AF. Catecholamine and second messenger influences on prefrontal cortical networks of „representational knowledge”: A rational bridge between genetics and the symptoms of mental illness.  Cereb Cortex. 2007;  , [Epub ahead of print]
• 8 Bearden CE, Jawad AF, Lynch DR, Sokol S, Kanes SJ, MacDonald-MacGinn DM. et al . Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome.  Am J Psychiatry. 2004;  161 1700-1702
• 9 Bertolino A, Breier A, Callicott JH, Adler C, Mattay VS, Shapiro M, Frank JA, Pickar D, Weinberger DR. The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia.  Neuropsychopharmacology. 2000;  22 125-132
• 10 Bertolino A, Caforio G, Blasi G, Candia M De, Latorre V, Petruzzella V. et al . Interaction ofCOMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.  Am J Psychiatry. 2004;  161 1798-1805
• 11 Bilder RM, Volavka J, Czobor P, Malhotra AK, Kennedy JL, Ni X. et al . Neurocognitive correlates of the COMT Val (158) Met polymorphism in chronic schizophrenia.  Biol Psychiatry. 2002;  52 701-707
• 12 Blackwood NJ, Howard RJ, Bentall RP, Murray RM. Cognitive neuropsychiatric models of persecutory delusions.  Am J Psychiatry. 2001;  158 527-539
• 13 Blank T, Nijholt I, Teichert U, Kügler H, Behrsing H, Fienberg A, Greengard P, Spiess J. The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses.  Proc Natl Acad Sci USA. 1997;  94 14859-14864
• 14 Breier A, Adler CM, Weisenfeld N, Su TP, Elman I, Picken L, Malhotra AK, Pickar D. Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach.  Synapse. 1998;  29 142-147
• 15 Brozoski T, Brown RM, Rosvold HE, Goldman PS. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.  Science. 1979;  205 929-931
• 16 Caille I, Dumartin B, Bloch B. Ultrastructural localization of D1 dopamine receptor immunoreactivity in rat striatonigral neurons and its relation with dopaminergic innervation.  Brain Res. 1996;  730 17-31
• 17 Carlsson A. The current status of the dopamine hypothesis of schizophrenia.  Neuropsychopharmacology. 1988;  1 179-186
• 18 Carlsson A. The neurochemical circuitry of schizophrenia.  Pharmacopsychiatry. 2006;  39 ((Suppl 1)) S10-S14
• 19 Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S. et al . Functional analysis of genetic variation in COMT: Effects on mRNA, protein and enzyme activity in postmortem brain.  Am J Hum Genet. 2004;  75 807-821
• 20 Chen L, Bohanick JD, Nishihara M, Seamans JK, Yang CR. Dopamine D1/5 receptor-mediated long-term potentiation of intrinsic excitability in rat prefrontal cortical neurons: Ca2⁺-dependent intracellular signaling.  J Neurophysiol. 2007;  97 2448-2464
• 21 Delle Donne KT, Sesack SR, Pickel VM. Ultrastructural immunocytochemical localization of neurotensin and the dopamine D2 receptor in the rat nucleus accumbens.  J Comp Neurol. 1996;  371 552-566
• 22 Deutch AY. The regulation of subcortical dopamine systems by the prefrontal cortex: interactions of central dopamine systems and the pathogenesis of schizophrenia.  J Neural Transm Suppl. 1992;  36 61-89
• 23 Diamond A, Briand L, Fossella J, Gehlbach L. Genetic and neurochemical modulation of prefrontal functions in children.  Am J Psychiatry. 2004;  161 125-132
• 24 Dierks T, Linden DE, Jandl M, Formisano E, Goebel R, Lanfermann H, Singer W. Activation of Heschl's gyrus during auditory hallucinations.  Neuron. 1999;  22 615-621
• 25 Durstewitz D. A few important pointds about dopamine's role in neural network dynamics.  Pharmacopsychiatry. 2006;  1 ((Suppl 1)) 72-75
• 26 Durstewitz D, Seamans JK, Sejnowski TJ. Neurocomputational models of working memory.  Nat Neurosci. 2000;  ((Suppl 3)) 1184-1191
• 27 Durstewitz D, Seamans JK. The computational role of dopamine D1 receptors in working memory.  Neural Netw. 2002;  15 561-572
• 28 Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE. et al . Effect ofCOMTVal108/158Met genotype on frontal lobe function and risk for schizophrenia.  Proc Natl Acad Sci USA. 2001;  98 6917-6922
• 29 Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, He L. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.  Biol Psychiatry. 2005;  57 139-144
• 30 Fienberg AA, Hiroi N, Mermelstein PG, Song W, Snyder GL, Nishi A, Cheramy A, O'Callaghan JP, Miller DB, Cole DG, Corbett R, Haile CN, Cooper DC, Onn SP, Grace AA, Ouimet CC, White FJ, Hyman SE, Surmeier DJ, Girault J, Nestler EJ, Greengard P. DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.  Science. 1998;  281 838-842
• 31 Fisher RS, Levine MS, Sibley DR, Ariano MA. D2 dopamine receptor protein location: Golgi impregnation-gold toned and ultrastructural analysis of the rat neostriatum.  J Neurosci Res. 1994;  38 551-564
• 32 Foltynie T, Goldberg TE, Lewis SG, Blackwell AD, Kolachana BS, Weinberger DR. et al . Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism.  Mov Disorder. 2004;  19 885-891
• 33 Gallinat J, Bajbouj M, Sander T, Schlattmann P, Ferro EF, Goldman D, Winterer G. Association of the G1947A COMT (Val(108/158)Met) gene polymorphism with prefrontal P300 during information processing.  Biol Psychiatry. 2003;  54 40-48
• 34 Glatt SJ, Faraone SV, Tsuang MT. Association between a functional catechol-O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies.  Am J Psychiatry. 2003;  160 469-476
• 35 Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D, Karayiorgou M. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorhic changes in catecholamine levels and behavior.  Proc Natl Acad Sci USA. 1998;  95 9991-9996
• 36 Goldberg TE, Egan MF, Gscheidle T, Coppola R, Weickert T, Kolachana BS. et al . Executive subprocesses in working memory: Relationship to COMT Val158Met genotype in schizophrenia.  Arch Gen Psychiatry. 2003;  60 889-896
• 37 Goldman-Rakic PS. Prefrontal cortical dysfunction in schizophrenia: the relevance of working memory. In: Carroll BJ, Barrett JE, eds. Psychopathology and the brain. New York: Raven Press 1991: 1-23
• 38 Grace AA. Cortical regulation of subcortical dopamine systems and ist possible relevance to schizophrenia.  J Neural Transm Genet Sect. 1993;  91 111-134
• 39 Greengard P. The neurobiology of slow synaptic transmission.  Science. 2001;  294 1024-1030
• 40 Guo N, Hwang DR, Lo ES, Huang YY, Laruelle M, Abi-Dargham A. Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia.  Neuropsychopharmacology. 2003;  28 1703-1711
• 41 Gurden H, Takita M, Jay TM. Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo.  J Neurosci. 2000;  20 RC106
• 42 Hallett PJ, Spoelgen R, Hyman BT, Standaert DG, Dunah AW. Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking.  J Neurosci. 2006;  26 4690-4700
• 43 Hemmings  Jr  HC, Girault JA, Nairn AC, Bertuzzi G, Greengard P. Distribution of protein phosphatase inhibitor-1 in brain and peripheral tissues of various species: comparison with DARPP-32.  J Neurochem. 1992;  59 1053-1061
• 44 Hersch SM, Ciliax BJ, Gutekunst C-A, Rees HD, Heilman CJ, Yung KKL, Bolam JP, Ince E, Yi H, Levey AI. Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents.  J Neurosci. 1995;  15 5222-5237
• 45 Hotte M, Thuault S, Lachaise F, Dineley KT, Hemmings HC, Nairn AC, Jay TM. D1 receptor modulation of memory retrieval performance is associated with changes in pCREB and pDARPP-32 in rat prefrontal cortex.  Behav Brain Res. 2006;  171 127-133
• 46 Huang YY, Kandel ER. D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus.  Proc Natl Acad Sci USA. 1995;  92 2446-2450
• 47 Huang YY, Simpson E, Kellendonk C, Kandel ER. Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors.  Proc Natl Acad Sci USA. 2004;  101 3236-3241
• 48 Huotari M, Gogos JA, Karayiorgou M, Koponen O, Forsberg M, Raasmaja A. et al . Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice.  Eur J Neurosci. 2002;  15 246-256
• 49 Jackson JH. Selected writings. Taylor, J, ed. London: Hodder and Stoughton 1931
• 50 Jaskiw GE, Karoum FK, Weinberger DR. Persistent elevations in dopamine and its metabolites in the nucleus accumbens after mild subchronic stress in rats with ibotenic acid lesions of the medial prefrontal cortex.  Brain Res. 1990;  534 321-323
• 51 Karoum F, Chrapusta SJ, Egan MF. 3-methoxytyramine is the major metabolite of released dopamine in the rat frontal cortex: Reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model.  J Neurochem. 1994;  63 972-979
• 52 Kebabian JW, Calne DB. Multiple receptors for dopamine.  Nature. 1979;  277 93-96
• 53 Kircher TT, Liddle PF, Brammer MJ, Williams SC, Murray RM, MacGuire PK. Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study.  Arch Gen Psychiatry. 2001;  58 769-774
• 54 Konrad A, Winterer G. Disturbed Structural Connectivity in Schizophrenia-Primary Factor in Pathology or Epiphenomenon?.  Schizophr Bull. 2007;  , [Epub ahead of print]
• 55 Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders.  Pharmacogenetics. 1996;  6 243-250
• 56 Laruelle M, Abi-Dargham A, Dyck CH van, Gil R, D'Souza CD, Erdos J, MacCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.  Proc Natl Acad Sci USA. 1996;  93 9235-9240
• 57 Leuner K, Müller WE. The complexity of the dopaminergic synapses and their modulation by antipsychotics.  Pharmacopsychiatry. 2006;  ((Suppl 1)) 15-20
• 58 Li Y-H, Wirth T, Huotari M, Laitinen K, MacDonald E, Mannisto PT. No change of brain extracellular catecholamine levels after acute catechol-O-methyltransferase inhibition: A microdialysis study in anaesthetized rats.  Eur J Pharm. 1998;  356 127-137
• 59 Lindskog M, Svenningsson P, Fredholm BB, Greengard P, Fisone G. Activation of dopamine D2 receptors decreases DARPP-32 phosphorylation in striatonigral and striatopallidal projection neurons via different mechanisms.  Neuroscience. 1999;  88 1005-1008
• 60 Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J. Kinetics of human soluble and membrane-bound catechol-O-methyltransferase: A revised mechanism and description of the thermolabile variant of the enzyme.  Biochemistry. 1995;  34 4202-4210
• 61 Malhotra AK, Kestler LJ, Mazzanti C, Bates JA, Goldberg T, Goldman D. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition.  Am J Psychiatry. 2002;  159 652-654
• 62 Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM. et al . Catechol-O-methyltransferase mRNA expression in human and rat brain: Evidence for a role in cortical neuronal function.  Neuroscience. 2003;  116 127-137
• 63 Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF. et al . Catechol-O-methyltransferase val158met genotype and individual variation in the brain response to amphetamine.  Proc Natl Acad Sci USA. 2003;  100 6186-6191
• 64 Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia.  Nat Neurosci. 2002;  5 267-271
• 65 Meyer-Lindenberg A, Nichols T, Callicott JH, Ding J, Kolachana B, Buckholtz J, Mattay VS, Egan M, Weinberger DR. Impact of complex genetic variation in COMT on human brain function.  Mol Psychiatry. 2006;  11 867-877
• 66 Meyer-Lindenberg A, Straub RE, Lipska BK, Verchinski BA, Goldberg T, Callicott JH, Egan MF, Huffaker SS, Mattay VS, Kolachana B, Kleinman JE, Weinberger DR. Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition.  J Clin Invest. 2007;  117 672-682
• 67 Narendran R, Hwang DR, Slifstein M, Hwang Y, Huang Y, Ekelund J, Guillin O, Scher E, Martinez D, Laruelle M. Measurement of the proportion of D2 receptors configured in state of high affinity for agonists in vivo: a positron emission tomography study using [11C]N-propyl-norapomorphine and [11C]raclopride in baboons.  J Pharmacol Exp Ther. 2005;  315 80-90
• 68 Neve KA, Seamans JK, Trantham-Davidson H. Dopamine receptor signaling.  J Recept Signal Transduct Res. 2004;  24 165-205
• 69 Nicodemus KK, Luna A, Vakkalanka R, Goldberg T, Egan M, Straub RE, Weinberger DR. Further evidence for association between ErbB4 and schizophrenia and influence on cognitive intermediate phenotypes in healthy controls.  Mol Psychiatry. 2006;  11 1062-1065
• 70 Nicodemus KK, Kolachana BS, Vakkalanka R, Straub RE, Giegling I, Egan MF, Rujescu D, Weinberger DR. 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. 2007;  120 889-906
• 71 Nishi A, Bibb JA, Matsuyama S, Hamada M, Higashi H, Nairn AC, Greengard P. Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA receptors: distinct roles of calcineurin and protein phosphatase-2A.  J Neurochem. 2002;  81 832-841
• 72 Nuechterlein KH, Dawson ME. A heuristic vulnerability/stress model of schizophrenic episodes.  Schizophr Bulletin. 1984;  10 300-312
• 73 Otani S, Daniel H, Roisin MP, Crepel F. Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons.  Cereb Cortex. 2003;  13 1251-1256
• 74 Paulson PE, Robinson TE. Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats.  Synpapse. 1995;  19 56-65
• 75 Pycock CJ, Kerwin RW, Carter CJ. Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats.  Nature. 1980;  286 74-76
• 76 Rao SG, Williams GV, Goldman-Rakic PS. Destruction and creation of spatial tuning by disinhibition: GABA(A) blockade of prefrontal cortical neurons engaged by working memory.  J Neurosci. 2000;  20 485-494
• 77 Robinson TE. The neurobiology of amphetamine psychosis: Evidence from studies with an animal model. In: Nakazawa T, ed. Taniguchi Symposia on Brain Sciences, Vol 14, Biological Basis of Schizophrenia. Japan Scientific Societies Press, Tokyo 1991: 185-201
• 78 Rosa A, Peralta V, Cuesta MJ, Zarzuela A, Serrano F, Martinez-Larrea A, Fananas L. New evidence of association between COMT gene and prefrontal neurocognitive function in healthy individuals from sibling pairs discordant for psychosis.  Am J Psychiatry. 2004;  161 1110-1112
• 79 Roth RH, Tam SY, Ida Y, Yang JX, Deutch AY. Stress and the mesocorticolimbic dopamine systems.  Ann N Y Acad Sci. 1988;  537 138-147
• 80 Roy K, Murtie JC, El-Khodor BF, Edgar N, Sardi SP, Hooks BM, Benoit-Marand M, Chen C, Moore H, O'Donnell P, Brunner D, Corfas G. Loss of erbB signaling in oligodendrocytes alters myelin and dopaminergic function, a potential mechanism for neuropsychiatric disorders.  Proc Natl Acad Sci USA. 2007;  104 8131-8136
• 81 Sawaguchi T, Goldman-Rakic PS. D1 dopamine receptors in prefrontal cortex: involvement in working memory.  Science. 1991;  251 947-950
• 82 Sawaguchi T, Matsumura M, Kubota K. Catecholamine sensitivities of motor cortical neurons of the monkey.  Neurosci Lett. 1986;  66 135-140
• 83 Sawaguchi T, Matsumura M, Kubota K. Dopamine enhances the neuronal activity of spatial short-term memory task in the primate prefrontal cortex.  Neurosci Res. 1988;  5 465-473
• 84 Seamans JK, Durstewitz D, Christie BR, Stevens CF, Sejnowski TJ. Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons.  Proc Natl Acad Sci USA. 2001;  98 301-306
• 85 Seamans JK, Gorelova N, Dustewitz D, Yang CR. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons.  J Neurosci. 2001;  21 3628-3638
• 86 Seamans JK, Yang CR. The principal features and mechanisms of dopamine modulation in the prefrontal cortex.  Prog Neurobiol. 2004;  74 1-58
• 87 Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Takei N, Mori N. Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET.  Am J Psychiatry. 2001;  58 1206-1214
• 88 Sesack SR, Aoki C, Pickel VM. Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets.  J Neurosci. 1994;  14 88-106
• 89 Shannon CE. Communication in the presence of noise.  Proceedings of the IRE. 1949;  37 10-21 , Reprinted in Proceedings of the IEEE 1998; 86: 447-458
• 90 Smiley JF, Levey AI, Ciliax BJ, Goldman-Rakic PS. D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines.  Proc Natl Acad Sci USA. 1994;  91 5720-5724
• 91 Smith WB, Starck SR, Roberts RW, Schuman EM. Dopaminergic stimulation of local protein synthesis enhances surface expression of GluR1 and synaptic transmission in hippocampal neurons.  Neuron. 2005;  45 765-779
• 92 Snyder GL, Fienberg AA, Huganir RL, Greengard P. A dopamine/D1 receptor/protein kinase A/dopamine- and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor.  J Neurosci. 1998;  18 10297-10303
• 93 Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Harvey RP, Lai D, Zhou M, Brunner D, Mutel V, Gonzalo A, Lemke G, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Gurney ME, Kong A, Gulcher JR, Petursson H, Stefansson K. Neuregulin 1 and susceptibility to schizophrenia.  Am J Hum Genet. 2002;  71 877-892
• 94 Stoof JC, Kebabian JW. Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum.  Nature. 1981;  294 366-368
• 95 Svenningsson P, Tzavara ET, Carruthers R, Rachleff I, Wattler S, Nehls M, MacKinzie DL, Fienberg AA, Nomikos GG, Greengard P. Diverse psychotomimetics act through a common signaling pathway.  Science. 2003;  302 1412-1415
• 96 Svenningsson P, Nishi A, Fisone G, Girault JA, Nairn AC, Greengard P. DARPP-32: an integrator of neurotransmission.  Annu Rev Pharmacol Toxicol. 2004;  44 269-296
• 97 Tan HY, Chen Q, Sust S, Buckholtz JW, Meyers JD, Egan MF, Mattay VS, Meyer-Lindenberg A, Weinberger DR, Callicott JH. Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function.  Proc Natl Acad Sci USA. 2007;  104 12536-12541
• 98 Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia.  Proc Natl Acad Sci USA. 2001;  98 11650-11655
• 99 Trantham-Davidson H, Neely LC, Lavin A, Seamans JK. Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in prefrontal cortex.  J Neurosci. 2004;  24 10652-10659
• 100 Trantham-Davidson H, Kröner S, Seamans JK. Dopamine modulation of prefrontal cortex interneurons occurs independently of DARPP-32.  Cereb Cortex. 2007;  , [Epub ahead of print]
• 101 Tretter F, Scherer J. Schizophrenia, Neurobiology and the methodology of systemic modeling.  Pharmacopsychiatry. 2006;  1 ((Suppl 1)) 26-35
• 102 Tunbridge EM, Bannerman DM, Sharp T, Harrison PJ. Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex.  J Neurosci. 2004;  24 5331-5335
• 103 Vanderschuren LJ, Wardeh G, Vries TJ De, Mulder AH, Schoffelmeer AN. Opposing role of dopamine D1 and D2 receptors in modulation of rat nucleus accumbens noradrenaline release.  J Neurosci. 1999;  19 4123-4131
• 104 Venton BJ, Seipel AT, Phillips PE, Wetsel WC, Gitler D, Greengard P, Augustine GJ, Wightman RM. Cocaine increases dopamine release by mobilization of a synapsin-dependent reserve pool.  J Neurosci. 2006;  26 3206-3209
• 105 Verhoeff NP, Hussey D, Lee M, Tauscher J, Papatheodorou G, Wilson AA, Houle S, Kapur S. Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans.  Mol Psychiatry. 2002;  7 322-328
• 106 Vogeley K, Kupke C. Disturbances of time consciousness from a phenomenological and a neuroscientific perspective.  Schizophr Bull. 2007;  33 157-165
• 107 Walaas SI, Greengard P. DARPP-32, a dopamine- and adenosine 3′:5′-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. I. Regional and cellular distribution in the rat brain.  J Neurosci. 1984;  4 84-98
• 108 Wang XJ. Toward a profontal microcircuit model for cognitive deficits in schizophrenia.  Pharmacopsychiatry. 2006;  ((Suppl 1)) 80-88
• 109 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
• 110 Weickert TW, Goldberg TE, Mishara A, Apud JA, Kolachana BS, Egan MF, Weinberger DR. Catechol-O-methyltransferase val158met genotype predicts working memory response to antipsychotic medications.  Biol Psychiatry. 2004;  56 677-682
• 111 Weickert TW, Goldberg TE. First- and second-generation antipsychotic medication and cognitive processing in schizophrenia.  Curr Psychiatry Rep. 2005;  7 304-310
• 112 Weinberger DR. Implications of normal brain development fort he pathogenesis of schizophrenia.  Arch Gen Psychiatry. 1987;  44 660-669
• 113 Weinberger DR, Berman KF, Illowsky BP. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism.  Arch Gen Psychiatry. 1988;  45 609-615
• 114 Weinshilboum RM, Otterness DM, Szumlanski CL. Methylation pharmacogenetics: Catechol-O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase.  Annu Rev Pharmacol Toxicol. 1999;  39 19-52
• 115 Wiener N. Cybernetics or Control and Communication in the Animal and the Machine. MIT Press, Cambridge, MA 1948
• 116 Winterer G, Ziller M, Dorn H, Frick K, Mulert C, Wuebben Y, Herrmann WM, Coppola R. Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing.  Clin Neurophysiol. 2000;  111 837-849
• 117 Winterer G, Goldman D. Genetics of human prefrontal function.  Brain Res Brain Res Rev. 2003;  43 134-163
• 118 Winterer G, Coppola R, Goldberg TE, Egan MF, Jones DW, Sanchez CE, Weinberger DR. Prefrontal broadband noise, working memory, and genetic risk for schizophrenia.  Am J Psychiatry. 2004;  161 490-500
• 119 Winterer G, Weinberger DR. Genes, dopamine and cortical signal-to-noise ratio in schizophrenia.  Trends Neurosci. 2004;  27 683-690
• 120 Winterer G, Egan MF, Kolachana BS, Goldberg TE, Coppola R, Weinberger DR. Prefrontal electrophysiologic „noise” and catechol-O-methyltransferase genotype in schizophrenia.  Biol Psychiatry. 2006;  60 578-584
• 121 Winterer G, Musso F, Vucurevic G, Stoeter P, Konrad A, Seker B, Gallinat J, Dahmen N, Weinberger DR. COMT genotype predicts BOLD signal and noise characteristics in prefrontal circuits.  Neuroimage. 2006;  32 1722-1732
• 122 Winterer G, Musso F, Beckmann C, Mattay V, Egan MF, Jones DW, Callicott JH, Coppola R, Weinberger DR. Instability of prefrontal signal processing in schizophrenia.  Am J Psychiatry. 2006;  163 1960-1968
• 123 Winterer G. Cortical microcircuits in schizophrenia - the dopamine hypothesis revisited.  Pharmacopsychiatry. 2006;  93 ((Suppl 1)) S68-S71
• 124 Young CE, Yang CR. Dopamine D1-like receptor modulates layer- and frequency-specific short-term synaptic plasticity in rat prefrontal cortical neurons.  Eur J Neurosci. 2005;  21 3310-3320

Correspondence