Dopamine and psychosis: Theory, pathomechanisms and intermediate phenotypes

Neuroscience and Biobehavioral Reviews

Volumn 34, Issue 5, 2010, Pages 689-700

  Tost, Heike ^a,b   Alam, Tajvar ^b   Meyer Lindenberg, Andreas ^a,b,c  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^b Genes   (United States)

^c CENTRAL INSTITUTE OF MENTAL HEALTH   (Germany)

Author keywords

Dopamine; Dopamine hypothesis; Imaging genetics; Intermediate phenotypes; Prefrontal function; Psychosis; Schizophrenia; Striatum; Susceptibility genes

Indexed keywords

CATECHOL METHYLTRANSFERASE; DOPAMINE; DOPAMINE 2 RECEPTOR; GLUTAMIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHOSPHOPROTEIN DARPP 32; PROLINE DEHYDROGENASE; PROTEIN KINASE B;

AUTOPSY; DISEASE ASSOCIATION; DOPAMINERGIC TRANSMISSION; FRONTAL LOBE; GENETIC RISK; GENETIC SUSCEPTIBILITY; HUMAN; MOLECULAR MECHANICS; NERVE CELL NETWORK; NEUROIMAGING; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PSYCHOSIS; REVIEW; RISK FACTOR; SCHIZOPHRENIA;

ANIMALS; BRAIN; DOPAMINE; HUMANS; MENTAL DISORDERS; MODELS, NEUROLOGICAL; PHENOTYPE;

EID: 77949268343     PISSN: 01497634     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neubiorev.2009.06.005     Document Type: Review

References (132)

1. Aalto S., Ihalainen J., Hirvonen J., Kajander J., Scheinin H., Tanila H., Nagren K., Vilkman H., Gustafsson L.L., Syvalahti E., and Hietala J. Cortical glutamate-dopamine interaction and ketamine-induced psychotic symptoms in man. Psychopharmacology (Berl.) 182 (2005) 375-383
2. Abi-Dargham A., Mawlawi O., Lombardo I., Gil R., Martinez D., Huang Y., Hwang D.R., Keilp J., Kochan L., Van Heertum R., Gorman J.M., and Laruelle M. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J. Neurosci. 22 (2002) 3708-3719
3. Abi-Dargham A., Rodenhiser J., Printz D., Zea-Ponce Y., Gil R., Kegeles L.S., Weiss R., Cooper T.B., Mann J.J., Van Heertum R.L., Gorman J.M., and Laruelle M. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 8104-8109
4. Albert K.A., Hemmings Jr. H.C., Adamo A.I., Potkin S.G., Akbarian S., Sandman C.A., Cotman C.W., Bunney Jr. W.E., and Greengard P. Evidence for decreased DARPP-32 in the prefrontal cortex of patients with schizophrenia. Arch. Gen. Psychiatry 59 (2002) 705-712
5. Arinami T., Gao M., Hamaguchi H., and Toru M. A functional polymorphism in the promoter region of the dopamine D2 receptor gene is associated with schizophrenia. Hum. Mol. Genet. 6 (1997) 577-582
6. Arinami T., Itokawa M., Enguchi H., Tagaya H., Yano S., Shimizu H., Hamaguchi H., and Toru M. Association of dopamine D2 receptor molecular variant with schizophrenia. Lancet 343 (1994) 703-704
7. Beaulieu J.M., Sotnikova T.D., Marion S., Lefkowitz R.J., Gainetdinov R.R., and Caron M.G. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122 (2005) 261-273
8. Beaulieu J.M., Sotnikova T.D., Yao W.D., Kockeritz L., Woodgett J.R., Gainetdinov R.R., and Caron M.G. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 5099-5104
9. Bender H.U., Almashanu S., Steel G., Hu C.A., Lin W.W., Willis A., Pulver A., and Valle D. Functional consequences of PRODH missense mutations. Am. J. Hum. Genet. 76 (2005) 409-420
10. Berridge K.C., and Robinson T.E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?. Brain Res. Brain Res. Rev. 28 (1998) 309-369
11. Bertolino A., Fazio L., Caforio G., Blasi G., Rampino A., Romano R., Di Giorgio A., Taurisano P., Papp A., Pinsonneault J., Wang D., Nardini M., Popolizio T., and Sadee W. Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia. Brain (2008)
12. Callicott J.H., Mattay V.S., Bertolino A., Finn K., Coppola R., Frank J.A., Goldberg T.E., and Weinberger D.R. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb. Cortex 9 (1999) 20-26
13. Cardno A.G., Holmans P.A., Rees M.I., Jones L.A., McCarthy G.M., Hamshere M.L., Williams N.M., Norton N., Williams H.J., Fenton I., Murphy K.C., Sanders R.D., Gray M.Y., O'Donovan M.C., McGuffin P., and Owen M.J. A genomewide linkage study of age at onset in schizophrenia. Am. J. Med. Genet. 105 (2001) 439-445
14. Carlsson A. Evidence for a role of dopamine in extrapyramidal functions. Acta Neuroveg. (Wien.) 26 (1964) 484-493
15. Carlsson A. Biochemical and pharmacological aspects of parkinsonism. Acta Neurol. Scand. Suppl. 51 (1972) 11-42
16. Carlsson M.L., Carlsson A., and Nilsson M. Schizophrenia: from dopamine to glutamate and back. Curr. Med. Chem. 11 (2004) 267-277
17. Chen J., Lipska B.K., Halim N., Ma Q.D., Matsumoto M., Melhem S., Kolachana B.S., Hyde T.M., Herman M.M., Apud J., Egan M.F., Kleinman J.E., and Weinberger D.R. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet. 75 (2004) 807-821
18. Chugani D.C., Ackermann R.F., and Phelps M.E. In vivo [3H]spiperone binding: evidence for accumulation in corpus striatum by agonist-mediated receptor internalization. J. Cereb. Blood Flow Metab. 8 (1988) 291-303
19. Corlett P.R., Murray G.K., Honey G.D., Aitken M.R., Shanks D.R., Robbins T.W., Bullmore E.T., Dickinson A., and Fletcher P.C. Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions. Brain 130 (2007) 2387-2400
20. Davis K.L., Kahn R.S., Ko G., and Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am. J. Psychiatry 148 (1991) 1474-1486
21. Delay J., Deniker P., and Harl J.M. Utilisation en therapeutique psychiatrique d'une phenothiazine d'action centrale elective (4560 RP). Ann. Med. Psychol. (Paris) 110 (1952) 112-117
22. Domyo T., Kurumaji A., and Toru M. An increase in [3H]SCH23390 binding in the cerebral cortex of postmortem brains of chronic schizophrenics. J. Neural Transm. 108 (2001) 1475-1484
23. Durstewitz D., and Seamans J.K. The dual-state theory of prefrontal cortex dopamine function with relevance to catechol-O-methyltransferase genotypes and schizophrenia. Biol. Psychiatry (2008)
24. 108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 6917-6922
25. Egan M.F., Straub R.E., Goldberg T.E., Yakub I., Callicott J.H., Hariri A.R., Mattay V.S., Bertolino A., Hyde T.M., Shannon-Weickert C., Akil M., Crook J., Vakkalanka R.K., Balkissoon R., Gibbs R.A., Kleinman J.E., and Weinberger D.R. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 12604-12609
26. Emamian E.S., Hall D., Birnbaum M.J., Karayiorgou M., and Gogos J.A. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat. Genet. 36 (2004) 131-137
27. Fan J.B., Zhang C.S., Gu N.F., Li X.W., Sun W.W., Wang H.Y., Feng G.Y., St Clair D., and He L. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol. Psychiatry 57 (2005) 139-144
28. Farde L., Pauli S., Hall H., Eriksson L., Halldin C., Hogberg T., Nilsson L., Sjogren I., and Stone-Elander S. Stereoselective binding of 11C-raclopride in living human brain-a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology (Berl.) 94 (1988) 471-478
29. Farde L., Wiesel F.A., Hall H., Halldin C., Stone-Elander S., and Sedvall G. No D2 receptor increase in PET study of schizophrenia. Arch. Gen. Psychiatry 44 (1987) 671-672
30. Farde L., Wiesel F.A., Stone-Elander S., Halldin C., Nordstrom A.L., Hall H., and Sedvall G. D2 dopamine receptors in neuroleptic-naïve schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch. Gen. Psychiatry 47 (1990) 213-219
31. Fernandez E., Schiappa R., Girault J.A., and Le Novere N. DARPP-32 is a robust integrator of dopamine and glutamate signals. PLoS Comput. Biol. 2 (2006) e176
32. Fuster J.M. Prefrontal cortex and the bridging of temporal gaps in the perception-action cycle. Ann. NY Acad. Sci. 608 (1990) 318-329 (discussion 330-316)
33. Genduso L.A., and Haley J.C. Cost of illness studies for schizophrenia: components, benefits, results, and implications. Am. J. Man Care 3 (1997) 873-877
34. Glaser B., Moskvina V., Kirov G., Murphy K.C., Williams H., Williams N., Owen M.J., and O'Donovan M.C. Analysis of ProDH, COMT and ZDHHC8 risk variants does not support individual or interactive effects on schizophrenia susceptibility. Schizophr. Res. 87 (2006) 21-27
35. Glatt S.J., Faraone S.V., Lasky-Su J.A., Kanazawa T., Hwu H.G., and Tsuang M.T. Family-based association testing strongly implicates DRD2 as a risk gene for schizophrenia in Han Chinese from Taiwan. Mol. Psychiatry (2008)
36. Glatt S.J., Faraone S.V., and Tsuang M.T. Meta-analysis identifies an association between the dopamine D2 receptor gene and schizophrenia. Mol. Psychiatry 8 (2003) 911-915
37. Gogos J.A., Santha M., Takacs Z., Beck K.D., Luine V., Lucas L.R., Nadler J.V., and Karayiorgou M. The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat. Genet. 21 (1999) 434-439
38. Goldberg T.E., Egan M.F., Gscheidle T., Coppola R., Weickert T., Kolachana B.S., Goldman D., and Weinberger D.R. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch. Gen. Psychiatry 60 (2003) 889-896
39. Goldberg T.E., Ragland J.D., Torrey E.F., Gold J.M., Bigelow L.B., and Weinberger D.R. Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Arch. Gen. Psychiatry 47 (1990) 1066-1072
40. Goldman-Rakic P.S. Cellular basis of working memory. Neuron 14 (1995) 477-485
41. Goldman-Rakic P.S., Muly III E.C., and Williams G.V. D(1) receptors in prefrontal cells and circuits. Brain Res. Brain Res. Rev. 31 (2000) 295-301
42. Goldsmith S.K., Shapiro R.M., and Joyce J.N. Disrupted pattern of D2 dopamine receptors in the temporal lobe in schizophrenia. A postmortem study. Arch. Gen. Psychiatry 54 (1997) 649-658
43. Gurevich E.V., Bordelon Y., Shapiro R.M., Arnold S.E., Gur R.E., and Joyce J.N. Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study. Arch. Gen. Psychiatry 54 (1997) 225-232
44. Hamon, Paraire, and Velluz. Remarques sur l'action du 4560 R. P. sur l'agitation maniaque. Ann. Med. Psychol. (Paris) 110 (1952) 331-335
45. Harrison P.J. Advances in post mortem molecular neurochemistry and neuropathology: examples from schizophrenia research. Br. Med. Bull. 52 (1996) 527-538
46. Harrison P.J., and Weinberger D.R. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry 10 (2005) 40-68 image 45
47. Heck A.H., de Groot I.W., and van Harten P.N. Addition of lamotrigine to clozapine in inpatients with chronic psychosis. J. Clin. Psychiatry 66 (2005) 1333
48. Hess E.J., Bracha H.S., Kleinman J.E., and Creese I. Dopamine receptor subtype imbalance in schizophrenia. Life Sci. 40 (1987) 1487-1497
49. Hirvonen J., van Erp T.G., Huttunen J., Aalto S., Nagren K., Huttunen M., Lonnqvist J., Kaprio J., Hietala J., and Cannon T.D. Increased caudate dopamine D2 receptor availability as a genetic marker for schizophrenia. Arch. Gen. Psychiatry 62 (2005) 371-378
50. Hosak L., and Libiger J. Antiepileptic drugs in schizophrenia: a review. Eur. Psychiatry 17 (2002) 371-378
51. Ishikawa M., Mizukami K., Iwakiri M., and Asada T. Immunohistochemical and immunoblot analysis of Dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000 (DARPP-32) in the prefrontal cortex of subjects with schizophrenia and bipolar disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 31 (2007) 1177-1181
52. Itokawa M., Arinami T., Futamura N., Hamaguchi H., and Toru M. A structural polymorphism of human dopamine D2 receptor, D2(Ser311 → Cys). Biochem. Biophys. Res. Commun. 196 (1993) 1369-1375
53. Jacquet H., Demily C., Houy E., Hecketsweiler B., Bou J., Raux G., Lerond J., Allio G., Haouzir S., Tillaux A., Bellegou C., Fouldrin G., Delamillieure P., Menard J.F., Dollfus S., D'Amato T., Petit M., Thibaut F., Frebourg T., and Campion D. Hyperprolinemia is a risk factor for schizoaffective disorder. Mol. Psychiatry 10 (2005) 479-485
54. Jacquet H., Raux G., Thibaut F., Hecketsweiler B., Houy E., Demilly C., Haouzir S., Allio G., Fouldrin G., Drouin V., Bou J., Petit M., Campion D., and Frebourg T. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum. Mol. Genet. 11 (2002) 2243-2249
55. Jensen J., Willeit M., Zipursky R.B., Savina I., Smith A.J., Menon M., Crawley A.P., and Kapur S. The formation of abnormal associations in schizophrenia: neural and behavioral evidence. Neuropsychopharmacology 33 (2008) 473-479
56. Juckel G., Schlagenhauf F., Koslowski M., Wustenberg T., Villringer A., Knutson B., Wrase J., and Heinz A. Dysfunction of ventral striatal reward prediction in schizophrenia. NeuroImage 29 (2006) 409-416
57. Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am. J. Psychiatry 160 (2003) 13-23
58. Kapur S., Mizrahi R., and Li M. From dopamine to salience to psychosis-linking biology, pharmacology and phenomenology of psychosis. Schizophr. Res. 79 (2005) 59-68
59. Kempf L., Nicodemus K.K., Kolachana B., Vakkalanka R., Verchinski B.A., Egan M.F., Straub R.E., Mattay V.A., Callicott J.H., Weinberger D.R., and Meyer-Lindenberg A. Functional polymorphisms in PRODH are associated with risk and protection for schizophrenia and fronto-striatal structure and function. PLoS Genet. 4 (2008) e1000252
60. Knable M.B., Hyde T.M., Herman M.M., Carter J.M., Bigelow L., and Kleinman J.E. Quantitative autoradiography of dopamine-D1 receptors, D2 receptors, and dopamine uptake sites in postmortem striatal specimens from schizophrenic patients. Biol. Psychiatry 36 (1994) 827-835
61. Knable M.B., Hyde T.M., Murray A.M., Herman M.M., and Kleinman J.E. A postmortem study of frontal cortical dopamine D1 receptors in schizophrenics, psychiatric controls, and normal controls. Biol. Psychiatry 40 (1996) 1191-1199
62. Krieger S., Lis S., Janik H., Cetin T., Gallhofer B., and Meyer-Lindenberg A. Executive function and cognitive subprocesses in first-episode, drug-naive schizophrenia: an analysis of N-back performance. Am. J. Psychiatry 162 (2005) 1206-1208
63. Laruelle M., and Abi-Dargham A. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J. Psychopharmacol. 13 (1999) 358-371
64. Laruelle M., Abi-Dargham A., van Dyck C.H., Gil R., D'Souza C.D., Erdos J., McCance E., Rosenblatt W., Fingado C., Zoghbi S.S., Baldwin R.M., Seibyl J.P., Krystal J.H., Charney D.S., and Innis R.B. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 9235-9240
65. Lewis C.M., Levinson D.F., Wise L.H., DeLisi L.E., Straub R.E., Hovatta I., Williams N.M., Schwab S.G., Pulver A.E., Faraone S.V., Brzustowicz L.M., Kaufmann C.A., Garver D.L., Gurling H.M., Lindholm E., Coon H., Moises H.W., Byerley W., Shaw S.H., Mesen A., Sherrington R., O'Neill F.A., Walsh D., Kendler K.S., Ekelund J., Paunio T., Lonnqvist J., Peltonen L., O'Donovan M.C., Owen M.J., Wildenauer D.B., Maier W., Nestadt G., Blouin J.L., Antonarakis S.E., Mowry B.J., Silverman J.M., Crowe R.R., Cloninger C.R., Tsuang M.T., Malaspina D., Harkavy-Friedman J.M., Svrakic D.M., Bassett A.S., Holcomb J., Kalsi G., McQuillin A., Brynjolfson J., Sigmundsson T., Petursson H., Jazin E., Zoega T., and Helgason T. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am. J. Hum. Genet. 73 (2003) 34-48
66. Lewis D.A., Melchitzky D.S., Sesack S.R., Whitehead R.E., Auh S., and Sampson A. Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization. J. Comp. Neurol. 432 (2001) 119-136
67. Li T., Ma X., Sham P.C., Sun X., Hu X., Wang Q., Meng H., Deng W., Liu X., Murray R.M., and Collier D.A. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 129B (2004) 13-15
68. Lidow M.S., Goldman-Rakic P.S., Rakic P., and Innis R.B. Dopamine D2 receptors in the cerebral cortex: distribution and pharmacological characterization with [3H]raclopride. Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 6412-6416
69. Liu H., Heath S.C., Sobin C., Roos J.L., Galke B.L., Blundell M.L., Lenane M., Robertson B., Wijsman E.M., Rapoport J.L., Gogos J.A., and Karayiorgou M. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 3717-3722
70. Manoach D.S. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr. Res. 60 (2003) 285-298
71. Mattay V.S., Callicott J.H., Bertolino A., Heaton I., Frank J.A., Coppola R., Berman K.F., Goldberg T.E., and Weinberger D.R. Effects of dextroamphetamine on cognitive performance and cortical activation. NeuroImage 12 (2000) 268-275
72. Mattay V.S., Goldberg T.E., Fera F., Hariri A.R., Tessitore A., Egan M.F., Kolachana B., Callicott J.H., and Weinberger D.R. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. PNAS 100 (2003) 6186-6191
73. Meador-Woodruff J.H., Haroutunian V., Powchik P., Davidson M., Davis K.L., and Watson S.J. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. Arch. Gen. Psychiatry 54 (1997) 1089-1095
74. Meyer-Lindenberg A., Kohn P.D., Kolachana B., Kippenhan S., McInerney-Leo A., Nussbaum R., Weinberger D.R., and Berman K.F. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat. Neurosci. 8 (2005) 594-596
75. Meyer-Lindenberg A., Miletich R.S., Kohn P.D., Esposito G., Carson R.E., Quarantelli M., Weinberger D.R., and Berman K.F. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat. Neurosci. 5 (2002) 267-271
76. Meyer-Lindenberg A., Nichols T., Callicott J.H., Ding J., Kolachana B., Buckholtz J., Mattay V.S., Egan M., and Weinberger D.R. Impact of complex genetic variation in COMT on human brain function. Mol. Psychiatry 11 (2006) 867-877 797
77. Meyer-Lindenberg A., Straub R.E., Lipska B.K., Verchinski B.A., Goldberg T., Callicott J.H., Egan M.F., Huffaker S.S., Mattay V.S., Kolachana B., Kleinman J.E., and Weinberger D.R. Genetic evidence implicating DARPP-32 in human frontostriatal structure, function, and cognition. J. Clin. Invest. 117 (2007) 672-682
78. Meyer-Lindenberg A., and Weinberger D.R. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat. Rev. Neurosci. 7 (2006) 818-827
79. Mita T., Hanada S., Nishino N., Kuno T., Nakai H., Yamadori T., Mizoi Y., and Tanaka C. Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol. Psychiatry 21 (1986) 1407-1414
80. Mjorndal T., and Winblad B. Alteration of dopamine receptors in the caudate nucleus and the putamen in schizophrenic brain. Med. Biol. 64 (1986) 351-354
81. Murphy K.C. Schizophrenia and velo-cardio-facial syndrome. Lancet 359 (2002) 426-430
82. Murray G.K., Corlett P.R., Clark L., Pessiglione M., Blackwell A.D., Honey G., Jones P.B., Bullmore E.T., Robbins T.W., and Fletcher P.C. Substantia nigra/ventral tegmental reward prediction error disruption in psychosis. Mol. Psychiatry 13 239 (2008) 267-276
83. Nicodemus K.K., Kolachana B.S., Vakkalanka R., Straub R.E., Giegling I., Egan M.F., Rujescu D., and Weinberger D.R. 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. 120 (2007) 889-906
84. Nicodemus K.K., Marenco S., Batten A.J., Vakkalanka R., Egan M.F., Straub R.E., and Weinberger D.R. Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol. Psychiatry 13 (2008) 873-877
85. Okubo Y., Suhara T., Suzuki K., Kobayashi K., Inoue O., Terasaki O., Someya Y., Sassa T., Sudo Y., Matsushima E., Iyo M., Tateno Y., and Toru M. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 385 (1997) 634-636
86. Owen M.J., Williams N.M., and O'Donovan M.C. The molecular genetics of schizophrenia: new findings promise new insights. Mol. Psychiatry 9 (2004) 14-27
87. Pantelis C., Barnes T.R., Nelson H.E., Tanner S., Weatherley L., Owen A.M., and Robbins T.W. Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain 120 Pt 10 (1997) 1823-1843
88. Parra L.A., Baust T.B., El Mestikawy S., Quiroz M., Hoffman B., Haflett J.M., Yao J.K., and Torres G.E. The orphan transporter Rxt1/NTT4 (SLC6A17) functions as a synaptic vesicle amino acid vesicular transporter selective for proline, glycine, leucine, and alanine. Mol. Pharmacol. (2008)
89. Paterlini M., Zakharenko S.S., Lai W.S., Qin J., Zhang H., Mukai J., Westphal K.G., Olivier B., Sulzer D., Pavlidis P., Siegelbaum S.A., Karayiorgou M., and Gogos J.A. Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat. Neurosci. 8 (2005) 1586-1594
90. Prentice K.J., Gold J.M., and Buchanan R.W. The Wisconsin Card Sorting impairment in schizophrenia is evident in the first four trials. Schizophr. Res. 106 (2008) 81-87
91. Raux G., Bumsel E., Hecketsweiler B., van Amelsvoort T., Zinkstok J., Manouvrier-Hanu S., Fantini C., Breviere G.M., Di Rosa G., Pustorino G., Vogels A., Swillen A., Legallic S., Bou J., Opolczynski G., Drouin-Garraud V., Lemarchand M., Philip N., Gerard-Desplanches A., Carlier M., Philippe A., Nolen M.C., Heron D., Sarda P., Lacombe D., Coizet C., Alembik Y., Layet V., Afenjar A., Hannequin D., Demily C., Petit M., Thibaut F., Frebourg T., and Campion D. Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum. Mol. Genet. 16 (2007) 83-91
92. Richardson N.R., and Gratton A. Behavior-relevant changes in nucleus accumbens dopamine transmission elicited by food reinforcement: an electrochemical study in rat. J. Neurosci. 16 (1996) 8160-8169
93. Rolls E.T., Loh M., Deco G., and Winterer G. Computational models of schizophrenia and dopamine modulation in the prefrontal cortex. Nat. Rev. Neurosci. 9 (2008) 696-709
94. Sawaguchi T., and Goldman-Rakic P.S. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251 (1991) 947-950
95. Schultz W., Apicella P., Scarnati E., and Ljungberg T. Neuronal activity in monkey ventral striatum related to the expectation of reward. J. Neurosci. 12 (1992) 4595-4610
96. Schultz W., Dayan P., and Montague P.R. A neural substrate of prediction and reward. Science 275 (1997) 1593-1599
97. Schwab S.G., Hoefgen B., Hanses C., Hassenbach M.B., Albus M., Lerer B., Trixler M., Maier W., and Wildenauer D.B. Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families. Biol. Psychiatry 58 (2005) 446-450
98. Seamans J.K., Floresco S.B., and Phillips A.G. D1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat. J. Neurosci. 18 (1998) 1613-1621
99. Seamans J.K., Gorelova N., Durstewitz D., and Yang C.R. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J. Neurosci. 21 (2001) 3628-3638
100. Seamans J.K., and Yang C.R. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog. Neurobiol. 74 (2004) 1-58
101. Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1 (1987) 133-152
102. Seeman P., Chau-Wong M., Tedesco J., and Wong K. Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc. Natl. Acad. Sci. U.S.A. 72 (1975) 4376-4380
103. Shafqat S., Velaz-Faircloth M., Henzi V.A., Whitney K.D., Yang-Feng T.L., Seldin M.F., and Fremeau Jr. R.T. Human brain-specific l-proline transporter: molecular cloning, functional expression, and chromosomal localization of the gene in human and mouse genomes. Mol. Pharmacol. 48 (1995) 219-229
104. Shifman S., Bronstein M., Sternfeld M., Pisante-Shalom A., Lev-Lehman E., Weizman A., Reznik I., Spivak B., Grisaru N., Karp L., Schiffer R., Kotler M., Strous R.D., Swartz-Vanetik M., Knobler H.Y., Shinar E., Beckmann J.S., Yakir B., Risch N., Zak N.B., and Darvasi A. A highly significant association between a COMT haplotype and schizophrenia. Am. J. Hum. Genet. 71 (2002) 1296-1302
105. Stefansson H., Rujescu D., Cichon S., Pietilainen O.P., Ingason A., Steinberg S., Fossdal R., Sigurdsson E., Sigmundsson T., Buizer-Voskamp J.E., Hansen T., Jakobsen K.D., Muglia P., Francks C., Matthews P.M., Gylfason A., Halldorsson B.V., Gudbjartsson D., Thorgeirsson T.E., Sigurdsson A., Jonasdottir A., Jonasdottir A., Bjornsson A., Mattiasdottir S., Blondal T., Haraldsson M., Magnusdottir B.B., Giegling I., Moller H.J., Hartmann A., Shianna K.V., Ge D., Need A.C., Crombie C., Fraser G., Walker N., Lonnqvist J., Suvisaari J., Tuulio-Henriksson A., Paunio T., Toulopoulou T., Bramon E., Di Forti M., Murray R., Ruggeri M., Vassos E., Tosato S., Walshe M., Li T., Vasilescu C., Muhleisen T.W., Wang A.G., Ullum H., Djurovic S., Melle I., Olesen J., Kiemeney L.A., Franke B., Sabatti C., Freimer N.B., Gulcher J.R., Thorsteinsdottir U., Kong A., Andreassen O.A., Ophoff R.A., Georgi A., Rietschel M., Werge T., Petursson H., Goldstein D.B., Nothen M.M., Peltonen L., Collier D.A., St Clair D., Stefansson K., Kahn R.S., Linszen D.H., van Os J., Wiersma D., Bruggeman R., Cahn W., de Haan L., Krabbendam L., and Myin-Germeys I. Large recurrent microdeletions associated with schizophrenia. Nature 455 (2008) 232-236
106. Stone J.M., Morrison P.D., and Pilowsky L.S. Glutamate and dopamine dysregulation in schizophrenia-a synthesis and selective review. J. Psychopharmacol. 21 (2007) 440-452
107. Strafella A.P., Paus T., Fraraccio M., and Dagher A. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126 (2003) 2609-2615
108. Straub R.E., Lipska B.K., Egan M.F., Goldberg T.E., Callicott J.H., Mayhew M.B., Vakkalanka R.K., Kolachana B.S., Kleinman J.E., and Weinberger D.R. Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol. Psychiatry 12 (2007) 854-869
109. Suhara T., Okubo Y., Yasuno F., Sudo Y., Inoue M., Ichimiya T., Nakashima Y., Nakayama K., Tanada S., Suzuki K., Halldin C., and Farde L. Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia. Arch. Gen. Psychiatry 59 (2002) 25-30
110. Sullivan P.F., Kendler K.S., and Neale M.C. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60 (2003) 1187-1192
111. Sullivan P.F., Neale M.C., and Kendler K.S. Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry 157 (2000) 1552-1562
112. Svenningsson P., Nishi A., Fisone G., Girault J.A., Nairn A.C., and Greengard P. DARPP-32: an integrator of neurotransmission. Annu. Rev. Pharmacol. Toxicol. 44 (2004) 269-296
113. Svenningsson P., Tzavara E.T., Carruthers R., Rachleff I., Wattler S., Nehls M., McKinzie D.L., Fienberg A.A., Nomikos G.G., and Greengard P. Diverse psychotomimetics act through a common signaling pathway. Science 302 (2003) 1412-1415
114. Svenningsson P., Tzavara E.T., Liu F., Fienberg A.A., Nomikos G.G., and Greengard P. DARPP-32 mediates serotonergic neurotransmission in the forebrain. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 3188-3193
115. Swerdlow N.R., Geyer M.A., and Braff D.L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl.) 156 (2001) 194-215
116. Tan H.Y., Chen Q., Sust S., Buckholtz J.W., Meyers J.D., Egan M.F., Mattay V.S., Meyer-Lindenberg A., Weinberger D.R., and Callicott J.H. Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 12536-12541
117. Tan H.Y., Nicodemus K.K., Chen Q., Li Z., Brooke J.K., Honea R., Kolachana B.S., Straub R.E., Meyer-Lindenberg A., Sei Y., Mattay V.S., Callicott J.H., and Weinberger D.R. Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans. J. Clin. Invest. 118 (2008) 2200-2208
118. Tost H., Meyer-Lindenberg A., Klein S., Schmitt A., Hohn F., Tenckhoff A., Ruf M., Ende G., Rietschel M., Henn F.A., and Braus D.F. D2 antidopaminergic modulation of frontal lobe function in healthy human subjects. Biol. Psychiatry 60 (2006) 1196-1205
119. Tunbridge E.M., Harrison P.J., and Weinberger D.R. Catechol-O-methyltransferase, cognition, and psychosis: Val(158)Met and beyond. Biol. Psychiatry (2006)
120. Van Rossum J.M. The significance of dopamine-receptor blockade for the mechanism of action of neuroleptic drugs. Arch. Int. Pharmacodyn. Ther. 160 (1966) 492-494
121. Vollenweider F.X., Vontobel P., Oye I., Hell D., and Leenders K.L. Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans. J. Psychiatr. Res. 34 (2000) 35-43
122. Weinberger D.R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44 (1987) 660-669
123. Weinberger D.R. Genetic mechanisms of psychosis: in vivo and postmortem genomics. Clin. Ther. 27 Suppl. A (2005) S8-S15
124. Weinberger D.R. Schizophrenia drug says goodbye to dopamine. Nat. Med. 13 (2007) 1018-1019
125. Williams G.V., and Goldman-Rakic P.S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376 (1995) 572-575
126. Williams H.J., Williams N., Spurlock G., Norton N., Zammit S., Kirov G., Owen M.J., and O'Donovan M.C. Detailed analysis of PRODH and PsPRODH reveals no association with schizophrenia. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 120B (2003) 42-46
127. Wong D.F., Wagner Jr. H.N., Tune L.E., Dannals R.F., Pearlson G.D., Links J.M., Tamminga C.A., Broussolle E.P., Ravert H.T., Wilson A.A., Toung J.K., Malat J., Williams J.A., O'Tuama L.A., Snyder S.H., Kuhar M.J., and Gjedde A. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234 (1986) 1558-1563
128. Yaryura-Tobias J.A., Diamond B., and Merlis S. The action of l-dopa on schizophrenic patients (a preliminary report). Curr. Ther. Res. Clin. Exp. 12 (1970) 528-531
129. Yaryura-Tobias J.A., Wolpert A., Dana L., and Merlis S. Action of l-Dopa in drug induced extrapyramidalism. Dis. Nerv. Syst. 31 (1970) 60-63
130. Young L.T., Wong D.F., Goldman S., Minkin E., Chen C., Matsumura K., Scheffel U., and Wagner Jr. H.N. Effects of endogenous dopamine on kinetics of [3H]N-methylspiperone and [3H]raclopride binding in the rat brain. Synapse 9 (1991) 188-194
131. Zawarynski P., Tallerico T., Seeman P., Lee S.P., O'Dowd B.F., and George S.R. Dopamine D2 receptor dimers in human and rat brain. FEBS Lett. 441 (1998) 383-386
132. Zoccali R., Muscatello M.R., Bruno A., Cambria R., Mico U., Spina E., and Meduri M. The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr. Res. 93 (2007) 109-116