Neuroreceptor imaging studies in schizophrenia

Harvard Review of Psychiatry

Volumn 15, Issue 5, 2007, Pages 212-232

  Frankle, W Gordon ^a,b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Dopamine; PET; Receptor occupancy; Schizophrenia; Serotonin; SPECT

Indexed keywords

5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE; 5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE C 11; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE; 8 CHLORO 2,3,4,5 TETRAHYDRO 3 METHYL 5 PHENYL 1H 3 BENZAZEPIN 7 OL HYDROGEN MALEATE C 11; AMISULPRIDE; AROMATIC LEVO AMINO ACID DECARBOXYLASE; CARBON 11; CLOZAPINE; DOPA; DOPA C 11; DOPAMINE; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE TRANSPORTER; EPIDEPRIDE; FLUORODOPA F 18; HALOPERIDOL; ISOREMOXIPRIDE; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; NEUROTRANSMITTER; OLANZAPINE; QUETIAPINE; RACLOPRIDE; RACLOPRIDE C 11; RADIOPHARMACEUTICAL AGENT; RISPERIDONE; SEROTONIN 1A RECEPTOR; SEROTONIN 2A RECEPTOR; SERTINDOLE; UNCLASSIFIED DRUG;

BRAIN; DOPAMINE RELEASE; DRUG DOSE COMPARISON; DRUG MECHANISM; DRUG MEGADOSE; DRUG RECEPTOR BINDING; EXTRAPYRAMIDAL SYMPTOM; HUMAN; LOW DRUG DOSE; NONHUMAN; PATHOPHYSIOLOGY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RECEPTOR DENSITY; RECEPTOR OCCUPANCY; REVIEW; SCHIZOPHRENIA; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; TARDIVE DYSKINESIA;

BRAIN; CORPUS STRIATUM; HUMANS; POSITRON-EMISSION TOMOGRAPHY; RECEPTORS, DOPAMINE; RECEPTORS, SENSORY; SCHIZOPHRENIA;

EID: 35048900928     PISSN: 10673229     EISSN: 14657309     Source Type: Journal    
DOI: 10.1080/10673220701679812     Document Type: Review

References (265)

1. Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991;148:1474-86.
2. Weinberger DR. Implications of the normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987;44:660-9.
3. Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ. A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 1984;15:217-27.
4. Slifstein M, Laruelle M. Models and methods for derivation of in vivo neuroreceptor parameters with PET and SPECT reversible radiotracers. Nucl Med Biol 2001;28:595-608.
5. Weinberger DR, Laruelle M. Neurochemical and neuropharmacological imaging in schizophrenia. In: Davis KL, Charney DS, Coyle JT, Nemeroff C, eds. Neuropharmacology - the fifth generation of progress. Philadelphia: Lippincott, Williams, & Wilkins, 2001.
6. Wong DF, Wagner HN, Tune LE, et al. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 1986;234:1558-63.
7. Crawley JC, Owens DG, Crow TJ, et al. Dopamine D2 receptors in schizophrenia studied in vivo. Lancet 1986;2:224-5.
8. Blin J, Baron JC, Cambon H, et al. Striatal dopamine D2 receptors in tardive dyskinesia: PET study. J Neurol Neurosurg Psychiatry 1989;52:1248-52.
9. Martinot J-L, Peron-Magnan P, Huret J-D, et al. Striatal D2 dopaminergic receptors assessed with positron emission tomography and 76-Br-bromospiperone in untreated patients. Am J Psychiatry 1990;147:346-50.
10. Tune LE, Wong DF, Pearlson G, et al. Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone. Psychiatry Res 1993;49:219-37.
11. Nordstrom AL, Farde L, Eriksson L, Halldin C. No elevated D2 dopamine receptors in neuroleptic-naive schizophrenic patients revealed by positron emission tomography and [11C]Nmethylspiperone. Psychiatry Res 1995;61:67-83 [see comments].
12. Okubo Y, Suhara T, Suzuki K, et al. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997;385:634-6.
13. Farde L, Wiesel F, Stone-Elander S, et al. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 1990;47:213-9.
14. Hietala J, Syvälahti E, Vuorio K, et al. Striatal D2 receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography. Arch Gen Psychiatry 1994;51:116-23.
15. Pilowsky LS, Costa DC, Ell PJ, Verhoeff NPLG, Murray RM, Kerwin RW. D2 dopamine receptor binding in the basal ganglia of antipsychotic-free schizophrenic patients. An I-123-IBZM single photon emission computerized tomography study. Br J Psychiatry 1994;164:16-26.
16. Laruelle M, Abi-Dargham A, van Dyck CH, et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug free schizophrenic subjects. Proc Natl Acad Sci U S A 1996;93:9235-40.
17. Knable MB, Egan MF, Heinz A, et al. Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia. [123I]-iodobenzamide SPECT study. Br J Psychiatry 1997;171:574-7.
18. Breier A, Su TP, Saunders R, et al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 1997;94:2569-74.
19. Abi-Dargham A, Gil R, Krystal J, et al. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 1998;155:761-7.
20. Abi-Dargham A, Rodenhiser J, Printz D, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 2000;97:8104-9.
21. Martinot JL, Paillère-Martinot ML, Loc'h C, et al. The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry 1991;158:346-50.
22. Martinot JL, Paillère-Martinot ML, Loc'h C, et al. Central D2 receptors and negative symptoms of schizophrenia. Br J Pharmacol 1994;164:27-34.
23. Seeman P, Guan H-C, Niznik HB. Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: Implications for positron emission tomography of the human brain. Synapse 1989;3:96-7.
24. Seeman P. Brain dopamine receptors in schizophrenia: PET problems. Arch Gen Psychiatry 1988;45:598-60.
25. Hirvonen J, van Erp TG, Huttunen J, et al. Increased caudate dopamine D2 receptor availability as a genetic marker for schizophrenia. Arch Gen Psychiatry 2005;62:371-8.
26. Karlsson P, Farde L, Halldin C, Sedvall G. D1-dopamine receptors in schizophrenia examined by PET. Schizophr Res 1997;24:179.
27. Abi-Dargham A, Mawlawi O, Lombardo I, et al. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 2002;22:3708-19.
28. Karlsson P, Farde L, Halldin C, Sedvall G. PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am J Psychiatry 2002;159:761-7.
29. Hirvonen J, van Erp TG, Huttunen J, et al. Brain dopamine d1 receptors in twins discordant for schizophrenia. Am J Psychiatry 2006;163:1747-53.
30. Joyce JN, Lexow N, Bird E, Winokur A. Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia. Synapse 1988;2:546-57.
31. Pimoule C, Schoemaker H, Reynolds GP, Langer SZ. [3H]SCH 23390 labelled D1 dopamine receptors are unchanged in schizophrenia and Parkinson's disease. Eur J Pharmacol 1985;114:235-7.
32. Seeman P, Bzowej NH, Guan HC, et al. Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases. Neuropsychopharmacology 1987;1:5-15.
33. Hess EJ, Bracha HS, Kleinman JE, Creese I. Dopamine receptor subtype imbalance in schizophrenia. Life Sci 1987;40:1487-97.
34. Reith J, Benkelfat C, Sherwin A, et al. Elevated dopa decarboxylase activity in living brain of patients with psychosis. Proc Natl Acad Sci U S A 1994;91:11651-4.
35. Hietala J, Syvalahti E, Vuorio K, et al. Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients. Lancet 1995;346:1130-1.
36. Dao-Castellana MH, Paillere-Martinot ML, Hantraye P, et al. Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophr Res 1997;23:167-74.
37. Hietala J, Syvalahti E, Vilkman H, et al. Depressive symptoms and presynaptic dopamine function in neuroleptic - naive schizophrenia. Schizophr Res 1999;35:41-50.
38. McGowan S, Lawrence AD, Sales T, Quested D, Grasby P. Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study. Arch Gen Psychiatry 2004;61:134-42.
39. Elkashef AM, Doudet D, Bryant T, Cohen RM, Li SH, Wyatt RJ. 6-(18)F-DOPA PET study in patients with schizophrenia. Positron emission tomography. Psychiatry Res 2000;100:1-11.
40. Lindstrom LH, Gefvert O, Hagberg G, et al. Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET. Biol Psychiatry 1999;46:681-8.
41. Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000;20:423-51.
42. Villemagne VL, Wong DF, Yokoi F, et al. GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans. Synapse 1999;33:268-73.
43. Laruelle M, Iyer RN, Al-Tikriti MS, et al. Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 1997;25:1-14.
44. Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R. Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 1999;46:56-72.
45. Hwang D, Kegeles LS, Laruelle M. (-)-N-[(11)C]propylnorapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors. Nucl Med Biol 2000;27:533-9.
46. Narendran R, Hwang DR, Slifstein M, et al. 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.
47. Laruelle M, DSouza CD, Baldwin RM, et al. Imaging D-2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology 1997;17:162-74.
48. Fujita M, Verhoeff NP, Varrone A, et al. Imaging extrastriatal dopamine D(2) receptor occupancy by endogenous dopamine in healthy humans. Eur J Pharmacol 2000;387:179-88.
49. Laruelle M, Abi-Dargham A, van Dyck C, et al. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [(123)I]beta-CIT. Biol Psychiatry 2000;47:371-9.
50. Laakso A, Vilkman H, Alakare B, et al. Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography. Am J Psychiatry 2000;157:269-71.
51. Laakso A, Bergman J, Haaparanta M, et al. Decreased striatal dopamine transporter binding in vivo in chronic schizophrenia. Schizophr Res 2001;52:115-20.
52. Lavalaye J, Linszen DH, Booij J, et al. Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT. Schizophr Res 2001;47:59-67.
53. Hsiao MC, Lin KJ, Liu CY, Tzen KY, Yen TC. Dopamine transporter change in drug-naive schizophrenia: an imaging study with 99mTc-TRODAT-1. Schizophr Res 2003;65:39-46.
54. Yoder KK, Hutchins GD, Morris ED, Brashear A, Wang C, Shekhar A. Dopamine transporter density in schizophrenic subjects with and without tardive dyskinesia. Schizophr Res 2004;71:371-5.
55. Yang YK, Yu L, Yeh TL, Chiu NT, Chen PS, Lee IH. Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study. Am J Psychiatry 2004;161:1496-8.
56. Mateos JJ, Lomena F, Parellada E, et al. Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism. Psychopharmacology (Berl) 2005;181:401-6.
57. Schmitt GJ, Meisenzahl EM, Frodl T, et al. The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand-[99mTc]TRODAT-1. J Psychopharmacol 2005;19:488-93.
58. Sjoholm H, Bratlid T, Sundsfjord J. 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia. Psychopharmacology (Berl) 2004;173:27-31.
59. Schmitt GJ, Frodl T, Dresel S, et al. Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug-naive schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 2006;256:115-21.
60. Robertson G, Fibiger H. Neuroleptics increase C-fos expression in the forebrain: contrasting effects of haloperidol and clozapine. Neuroscience 1992;46:315-28.
61. Robertson GS, Matsumura H, Fibiger HC. Induction patterns of fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity. J Pharmacol Exp Ther 1994;271:1058-66.
62. Deutch A, Moghadam B, Innis R, et al. Mechanisms of action of atypical antipsychotic drugs. Implication for novel therapeutic strategies for schizophrenia. Schizophr Res 1991;4:121-56.
63. Mawlawi O, Martinez D, Slifstein M, et al. Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D2 receptor parameter measurements in ventral striatum. J Cereb Blood Flow Metab 2001;21:1034-57.
64. Drevets WC, Gautier C, Price JC, et al. Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry 2001;49:81-96.
65. Martinez D, Slifstein M, Broft A, et al. Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J Cereb Blood Flow Metab 2003;23:285-300.
66. Halldin C, Farde L, Hogberg T, et al. Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. J Nucl Med 1995;36:1275-81.
67. Mukherjee J, Yang ZY, Das MK, Brown T. Fluorinated benzamide neuroleptics - III. Development of (S)-N-[(1-allyl- 2-pyrrolidinyl)methyl]-5-(3-[18F] fluoropropyl)-2, 3-dimethoxybenzamide as an improved dopamine D-2 receptor tracer. Nucl Med Biol 1995;22:283-96.
68. De Keyser J, Ebinger G, Vauquelin G. Evidence for a widespread dopaminergic innervation of the human cerebral neocortex. Neurosci Lett 1989;104:281-5.
69. Hall H, Sedvall G, Magnusson O, Kopp J, Halldin C, Farde L. Distribution of D1- and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology 1994;11:245-56.
70. Okubo Y, Suhara T, Suzuki K, et al. Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography. Life Sci 2000;66:2455-64.
71. Abi-Dargham A, Gil R, Mawlawi O, et al. Selective alteration in D1 receptors in schizophrenia: a PET in vivo study. J Nuc Med 2001;42:17P.
72. Abi-Dargham A, Moore H. Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia. Neuroscientist 2003;9:404-16.
73. Ekelund J, Narendran R, Guillian O, et al. Pharmacological selectivity of the in vivo binding of [11C]NNC112 and [11C]SCH233390 in the cortex: a PET study in baboons. NeuroImage 2006;31:T111.
74. Slifstein M, Kegeles LS, Gonzales R, et al. [(11)C]NNC 112 selectivity for dopamine D(1) and serotonin 5-HT(2A) receptors: a PET study in healthy human subjects. J Cereb Blood Flow Metab. Epub 2007 Feb 21.
75. Kessler RM, Whetsell WO, Ansari MS, et al. Identification of extrastriatal dopamine D2 receptors in postmortem human brain with [125I]epidipride. Brain Res 1993;609:237-43.
76. 2 receptors in the cerebral cortex: distribution and pharmacological characterization with [3H]raclopride. Proc Natl Acad Sci U S A 1989;86:6412-6.
77. Murray A, Ryoo HL, Gurevich E, Joyce JN. Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesofrontal regions of human forebrain. Proc Natl Acad Sci U S A 1994;91:11271-5.
78. Joyce JN, Janowsky A, Neve K. Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex in human brain. J Pharmacol Exp Ther 1991;257:1253-63.
79. Slifstein M, Hwang DR, Huang Y, et al. In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates. Psychopharmacology (Berl) 2004;175:274-86.
80. Talvik M, Nordstrom AL, Olsson H, Halldin C, Farde L. Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: a PET study with [11C]FLB 457. Int J Neuropsychopharmacol 2003;6:361-70.
81. Yasuno F, Suhara T, Okubo Y, et al. Low dopamine d(2) receptor binding in subregions of the thalamus in schizophrenia. Am J Psychiatry 2004;161:1016-22.
82. Buchsbaum MS, Christian BT, Lehrer DS, et al. D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia. Schizophr Res 2006;85:232-44.
83. Suhara T, Okubo Y, Yasuno F, et al. Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia. Arch Gen Psychiatry 2002;59:25-30.
84. Tuppurainen H, Kuikka JT, Laakso MP, Viinamaki H, Husso M, Tiihonen J. Midbrain dopamine D(2/3) receptor binding in schizophrenia. Eur Arch Psychiatry Clin Neurosci 2006;256:382-7.
85. Tuppurainen H, Kuikka J, Viinamaki H, Husso-Saastamoinen M, Bergstrom K, Tiihonen J. Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients. Mol Psychiatry 2003;8:453-5.
86. Glenthoj BY, Mackeprang T, Svarer C, et al. Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biol Psychiatry 2006;60;621-9.
87. Mukherjee J, Yang ZY, Lew R, et al. Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, F-18-fallypride in nonhuman primates using positron emission tomography. Synapse 1997;27:1-13.
88. Slifstein M, Narendran R, Hwang DR, et al. Effect of amphetamine on [(18)F]fallypride in vivo binding to D(2) receptors in striatal and extrastriatal regions of the primate brain: single bolus and bolus plus constant infusion studies. Synapse 2004;54:46-63.
89. Mukherjee J, Christian BT, Narayanan TK, Shi B, Collins D. Measurement of d-amphetamine-induced effects on the binding of dopamine D-2/D-3 receptor radioligand, 18F-fallypride in extrastriatal brain regions in non-human primates using PET. Brain Res 2005;1032:77-84.
90. Riccardi P, Li R, Ansari MS, et al. Amphetamine-induced displacement of [18F] fallypride in striatum and extrastriatal regions in humans. Neuropsychopharmacology 2006;31:1016-26.
91. Christian BT, Lehrer DS, Shi B, et al. Measuring dopamine neuromodulation in the thalamus: using [F-18]fallypride PET to study dopamine release during a spatial attention task. Neuroimage 2006;31:139-52.
92. Gaddum JH. Drug antagonistic to 5-hydroxytryptamine. In: Wolstenholme GW, ed. Ciba foundation symposium on hypertension. Boston: Little Brown, 1954:75-7.
93. Wooley DW, Shaw E. A biological and pharmacological suggestion about certain mental disorder. Proc Natl Acad Sci U S A 1954;40:228-31.
94. Aghajanian GK, Marek GJ. Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Res Brain Res Rev 2000;31:302-12.
95. Abi-Dargham A, Laruelle M, Aghajanian GK, Charney D, Krystal J. The role of serotonin in the pathophysiology and treatment of schizophrenia. J Neuropsych Clin Neurosci 1997;9:1-17.
96. Neumeyer JL, Wang S, Milius RA, et al. [123I]2β-carbomethoxy- 3β-(4-iodophenyl)tropane (β-CIT): high affinity SPECT radiotracer of monoamine reuptake sites in brain. J Med Chem 1991;34:3144-6.
97. Laruelle M, Baldwin RM, Malison RT, et al. SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 1993;13:295-309.
98. Frankle WG, Narendran R, Huang Y, et al. Serotonin transporter availability in patients with schizophrenia: a positron emission tomography imaging study with [11C]DASB. Biol Psychiatry 2005;57:1510-6.
99. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE. Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 1993;8:315-36.
100. Laruelle M, Abi-Dargham A, Casanova MF, Toti R, Weinberger DR, Kleinman JE. Selective abnormalities of prefrontal serotonergic receptors in schizophrenia: a postmortem study. Arch Gen Psychiatry 1993;50:810-8.
101. Gurevich EV, Joyce JN. Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biol Psychiatry 1997;42:529-45.
102. Dean B, Opeskin K, Pavey G, et al. [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. J Neurochem 1995;64:1197-202.
103. Naylor L, Dean B, Opeskin K, et al. Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine. J Neural Transm Gen Sect 1996;103:749-57.
104. Frankle WG, Huang Y, Hwang DR, et al. Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans. J Nucl Med 2004;45:682-94.
105. Huang Y, Hwang DR, Narendran R, et al. Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. J Cereb Blood Flow Metab 2002;22:1377-98.
106. Huang Y, Bae S-A, Zhu Z, Guo N, Hwang DR, Laruelle M. Fluorinated analogues of ADAM as new PET radioligands for the serotonin transporter: synthesis and pharmacological evaluation. J Labelled Compd Radiopharm 2001;44:S18-20.
107. Bennett JP, Enna SJ, Bylund DB, Gillin JC, Wyatt RJ, Snyder SH. Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 1979;36:927-34.
108. Whitaker PM, Crow TJ, Ferrier IN. Tritiated LSD binding in frontal cortex in schizophrenia. Arch Gen Psychiatry 1981;38:278-80.
109. Reynolds GP, Rossor MN, Ivesen LL. Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action. J Neural Transm 1983;suppl 18:273-7.
110. Mita T, Hanada S, Nishino N, et al. Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 1986;21:1407-14.
111. Arora RC, Meltzer HY. Serotonin2 (5-HT2) receptor binding in frontal cortex of schizophrenic patients. J Neural Transm 1991;85:19-29.
112. Dean B, Hayes W. Decreased frontal cortical serotonin2A receptors in schizophrenia. Schizophr Res 1996;21:133-9.
113. Burnet PW, Eastwood SL, Harrison PJ. 5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 1996;15:442-55.
114. Lewis R, Kapur S, Jones C, et al. Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects. Am J Psychiatry 1999;156:72-8.
115. Trichard C, Paillere-Martinot ML, Attar-Levy D, Blin J, Feline A, Martinot JL. No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET. Schizophr Res 1998;31:13-7.
116. Verhoeff NP, Meyer JH, Kecojevic A, et al. A voxel-by-voxel analysis of [18F]setoperone PET data shows no substantial serotonin 5-HT(2A) receptor changes in schizophrenia. Psychiatry Res 2000;99:123-35.
117. Ngan ET, Yatham LN, Ruth TJ, Liddle PF. Decreased serotonin 2A receptor densities in neuroleptic-naive patients with schizophrenia: a PET study using [(18)F]setoperone. Am J Psychiatry 2000;157:1016-8.
118. Burnet PWJ, Eastwood SL, Harrison PJ. [H-3]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [H-3]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia. Neurochem Int 1997;30:565-74.
119. Hashimoto T, Nishino N, Nakai H, Tanaka C. Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia. Life Sci 1991;48:355-63.
120. Simpson MD, Lubman DI, Slater P, Deakin JF. Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT(1A) receptors in ventral prefrontal cortex in schizophrenia. Biol Psychiatry 1996;39:919-28.
121. Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY. Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 1996;708:209-14.
122. Tauscher J, Kapur S, Verhoeff NP, et al. Brain serotonin 5-HT1A receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Arch Gen Psychiatry 2002;59:514-20.
123. Yasuno F, Suhara T, Ichimiya T, Takano A, Ando T, Okubo Y. Decreased 5-HT1A receptor binding in amygdala of schizophrenia. Biol Psychiatry 2004;55:439-44.
124. Frankle WG, Lombardo I, Kegeles LS, et al. Serotonin 1A receptor availability in patients with schizophrenia and schizoaffective disorder: a positron emission tomography imaging study with [(11)C]WAY 100635. Psychopharmacology (Berl) 2006;189:155-64.
125. Cruz DA, Eggan SM, Azmitia EC, Lewis DA. Serotonin1A receptors at the axon initial segment of prefrontal pyramidal neurons in schizophrenia. Am J Psychiatry 2004;161:739-42.
126. Lewis DA. GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Rev 2000;31:270-6.
127. Benes FM. Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev 2000;31:251-69.
128. Busatto GF, Pilowsky LS, Costa DC, et al. Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia. Am J Psychiatry 1997;154:56-63.
129. Verhoeff NP, Soares JC, D'Souza CD, et al. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Res 1999;91:163-73.
130. Abi-Dargham A, Laruelle M, Krystal J, et al. No evidence of altered in vivo benzodiazepine receptor binding in schizophrenia. Neuropsychopharmacology 1999;20:650-61.
131. Benes FM, Wickramasinghe R, Vincent SL, Khan Y, Todtenkopf M. Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain. Brain Res 1997;755:121-9.
132. Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 2005;6:312-24.
133. Raedler TJ, Knable MB, Jones DW, et al. In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry 2003;160:118-27.
134. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B. Decreased muscarinic receptor binding in subjects with schizophrenia: a study of the human hippocampal formation. Biol Psychiatry 2000;48:381-8.
135. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B. Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann's areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment. Am J Psychiatry 2001;158:918-25.
136. Dean B, Crook JM, Opeskin K, Hill C, Keks N, Copolov DL. The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia. Mol Psychiatry 1996;1:54-8.
137. Watanabe S, Nishikawa T, Takashima M, Toru M. Increased muscarinic cholinergic receptors in prefrontal cortices of medicated schizophrenics. Life Sci 1983;33:2187-96.
138. Owen F, Cross AJ, Crow TJ, Lofthouse R, Poulter M. Neurotransmitter receptors in brain in schizophrenia. Acta Psychiatr Scand Suppl 1981;291:20-8.
139. Yanai K, Tashiro M. The physiological and pathophysiological roles of neuronal histamine: an insight from human positron emission tomography studies. Pharmacol Ther 2007;113:1-15.
140. Iwabuchi K, Ito C, Tashiro M, et al. Histamine H1 receptors in schizophrenic patients measured by positron emission tomography. Eur Neuropsychopharmacol 2005;15:185-91.
141. Vander Borght T, Kilbourn M, Desmond T, Kuhl D, Frey K. The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. Eur J Pharmacol 1995;294:577-83.
142. Taylor SF, Koeppe RA, Tandon R, Zubieta JK, Frey KA. In vivo measurement of the vesicular monoamine transporter in schizophrenia. Neuropsychopharmacology 2000;23:667-75.
143. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990;264:2511-8.
144. Arseneault L, Cannon M, Witton J, Murray RM. Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry 2004;184:110-7.
145. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-9.
146. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:561-4.
147. Matsuda LA. Molecular aspects of cannabinoid receptors. Crit Rev Neurobiol 1997;11:143-66.
148. Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 1997;77:299-318.
149. Biegon A, Kerman IA. Autoradiographic study of pre- and postnatal distribution of cannabinoid receptors in human brain. Neuroimage 2001;14:1463-8.
150. Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A 1990;87:1932-6.
151. Pazos MR, Nunez E, Benito C, Tolon RM, Romero J. Functional neuroanatomy of the endocannabinoid system. Pharmacol Biochem Behav 2005;81:239-47.
152. Giuffrida A, Leweke FM, Gerth CW, et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 2004;29:2108-14.
153. Dean B, Sundram S, Bradbury R, Scarr E, Copolov D. Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use. Neuroscience 2001;103:9-15.
154. Zavitsanou K, Garrick T, Huang XF. Selective antagonist [3H]SR141716A binding to cannabinoid CB1 receptors is increased in the anterior cingulate cortex in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:355-60.
155. Horti A, Fan H, Ravert HT, et al. PET Imaging of cerebral cannabinoid CB1 receptors with [11C]JHU75528. J Nuc Med 2006;2006:136P.
156. Kapur S, Zipursky RB, Remington G. Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 1999;156:286-93.
157. Nyberg S, Nilsson U, Okubo Y, Halldin C, Farde L. Implications of brain imaging for the management of schizophrenia. Int Clin Psychopharmacol 1998;13 suppl 3:S15-20.
158. Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976;261:717-9.
159. Seeman P, Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 1975;188:1217-9.
160. Seeman P, Chau-Wong M, Tedesco J, Wong K. Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci U S A 1975;72:4376-80.
161. Farde L, Nordström AL, Wiesel FA, Pauli S, Halldin C, Sedvall G. Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 1992;49:538-44.
162. Wolkin A, Barouche F, Wolf AP, et al. Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry 1989;146:905-8.
163. Pilowsky LS, Costa DC, Ell PJ, Murray RM, Verhoeff NPLG, Kerwin RW. Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 1992;340:199-202.
164. Nordstrom AL, Farde L, Wiesel FA, et al. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry 1993;33:227-35.
165. Kapur S, Zipursky R, Jones C, Remington G, Houle S. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000;157:514-20.
166. Kane J, Honigfeld G, Singer J, Meltzer HY. Clozapine for the treatment-resistant schizophrenic. Arch Gen Psychiatry 1988;45:789-96.
167. Kane JM, Marder SR, Schooler NR, et al. Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Arch Gen Psychiatry 2001;58:965-72.
168. Kane JM. Extrapyramidal side effects are unacceptable. Eur Neuropsychopharmacol 2001;11 suppl 4:S397-403.
169. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry 2001;158:360-9.
170. Lidsky TI. Reevaluation of the mesolimbic hypothesis of antipsychotic drug action. Schizophr Bull 1995;21:67-74.
171. Meltzer HY, Matsubara S, Lee JC. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 1989;25:390-2.
172. Nordstrom AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G. D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry 1995;152:1444-9.
173. Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Increased dopamine d(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Am J Psychiatry 2001;158:311-4.
174. Chivers JK, Gommeren W, Leysen JE, Jenner P, Marsden CD. Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain
175. Leucht S, Pitschel-Walz G, Engel RR, Kissling W. Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry 2002;159:180-90.
176. Xiberas X, Martinot JL, Mallet L, et al. In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia. J Clin Psychopharmacol 2001;21:207-14.
177. Bressan RA, Erlandsson K, Jones HM, et al. Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? An in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients. Am J Psychiatry 2003;160:1413-20.
178. Vernaleken I, Siessmeier T, Buchholz HG, et al. High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia. Int J Neuropsychopharmacol 2004;7:421-30.
179. Gefvert O, Bergstrom M, Langstrom B, Lundberg T, Lindstrom L, Yates R. Time course of central nervous dopamine-D2 and 5-HT2 receptor blockade and plasma drug concentrations after discontinuation of quetiapine (Seroquel) in patients with schizophrenia. Psychopharmacology (Berl) 1998;135:119-26.
180. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P. A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry 2000;57:553-9.
181. Tauscher-Wisniewski S, Kapur S, Tauscher J, et al. Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade. J Clin Psychiatry 2002;63:992-7.
182. Kapur S, Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci 2000;25:161-6.
183. Meisenzahl EM, Dresel S, Frodl T, et al. D2 receptor occupancy under recommended and high doses of olanzapine: an iodine-123-iodobenzamide SPECT study. J Psychopharmacology 2000;14:364-70.
184. Raedler TJ, Knable MB, Lafargue T, et al. In vivo determination of striatal dopamine D2 receptor occupancy in patients treated with olanzapine. Psychiatry Res 1999;90:81-90.
185. Kapur S, Zipursky RB, Remington G, et al. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 1998;155:921-8.
186. Lavalaye J, Booij J, Linszen DH, Reneman L, van Royen EA. Higher occupancy of muscarinic receptors by olanzapine than risperidone in patients with schizophrenia. A[123I]-IDEX SPECT study. Psychopharmacology (Berl) 2001;156:53-7.
187. Raedler TJ, Knable MB, Jones DW, et al. In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. Neuropsychopharmacology 2000;23:56-68.
188. Anden NE. Dopamine turnover in the corpus striatum and the lumbic system after treatment with neuroleptic and anti-acetylcholine drugs. J Pharm Pharmacol 1972;24:905-6.
189. Anden N, Stock G. Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 1973;25:346-8.
190. Matthysse S. Dopamine and the pharmacology of schizophrenia: the state of the evidence. J Psychiatr Res 1974;11:107-13.
191. Matthysse S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Fed Proc 1973;32:200-5.
192. Snyder SH. Cathecolamines in the brain as mediator of amphetamine psychosis. Arch Gen Psychiatry 1972;27:169-79.
193. Stevens J. An anatomy of schizophrenia? Arch Gen Psychiatry 1973;29:177-89.
194. Deutch AY, Lee MC, Iadarola MJ. Regionally specific effects of atypical antipsychotic drugs on striatal fos expression: the nucleus accumbens shell as a locus of antipsychotic action. Mol Cell Neurosci 1992;3:332-41.
195. Robertson GS, Fibiger HC. Neuroleptics increase c-fos expression in the forebrain: contrasting effects of haloperidol and clozapine. Neuroscience 1992;46:315-28.
196. Grace AA, Bunney BS, Moore H, Todd CL. Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends Neurosci 1997;20:31-7.
197. Chiodo L, Bunney B. Typical and atypical neiroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 1983;3:1607-19.
198. White FJ, Wang RY. Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 1983:1054-7.
199. Pilowsky LS, Mulligan RS, Acton PD, Ell PJ, Costa DC, Kerwin RW. Limbic selectivity of clozapine. Lancet 1997;350:490-1.
200. Farde L, Suhara T, Nyberg S, et al. A PET study of [C-11]FLB 457 binding to extrastriatal D-2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients. Psychopharmacology 1997;133:396-404.
201. Bigliani V, Mulligan RS, Acton PD, et al. In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123I]epidepride single photon emission tomography (SPET) study. Br J Psychiatry 1999;175:231-8.
202. Bigliani V, Mulligan RS, Acton PD, et al. Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123I]epidepride single photon emission tomography (SPET) study. Psychopharmacology (Berl) 2000;150:132-40.
203. Stephenson C, Bigliani V, Jones H, et al. Striatal and extrastriatal D2/D3 dopamine receptor occupancy by quetiapine in vivo. Br J Psychiatry 2000;177:408-15.
204. Talvik M, Nordstrom AL, Nyberg S, Olsson H, Halldin C, Farde L. No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopride and [(11)C]FLB 457. Am J Psychiatry 2001;158:926-30.
205. Xiberas X, Martinot JL, Mallet L, et al. Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry 2001;179:503-8.
206. Yasuno F, Suhara T, Okubo Y, et al. Dose relationship of limbiccortical D2-dopamine receptor occupancy with risperidone. Psychopharmacology (Berl) 2001;154:112-4.
207. Bressan RA, Erlandsson K, Jones HM, Mulligan RS, Ell PJ, Pilowsky LS. Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study. J Clin Psychopharmacol 2003;23:5-14.
208. Kessler RM, Ansari MS, Riccardi P, et al. Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol. Neuropsychopharmacology 2005;30:2283-9.
209. Kessler RM, Ansari MS, Riccardi P, et al. Occupancy of striatal and extrastriatal dopamine D2 receptors by clozapine and quetiapine. Neuropsychopharmacology 2006;31:1991-2001.
210. Grunder G, Landvogt C, Vernaleken I, et al. The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia. Neuropsychopharmacology 2006;31:1027-35.
211. Agid O, Mamo D, Ginovart N, et al. Striatal vs extrastriatal dopamine D(2) receptors in antipsychotic response - a double-blind PET study in schizophrenia. Neuropsychopharmacology 2007;32:1209-15.
212. Olsson H, Farde L. Potentials and pitfalls using high affinity radioligands in PET and SPET determinations on regional drug induced D2 receptor occupancy - a simulation study based on experimental data. Neuroimage 2001;14:936-45.
213. Khan ZU, Mrzljak L, Gutierrez A, de la Calle A, Goldman-Rakic PS. Prominence of the dopamine D2 short isoform in dopaminergic pathways. Proc Natl Acad Sci U S A 1998;95:7731-6.
214. Karle J, Clemmesen L, Hansen L, et al. NNC 01-0687, a selective dopamine D1 receptor antagonist, in the treatment of schizophrenia. Psychopharmacology (Berl) 1995;121:328-9.
215. de Beaurepaire R, Labelle A, Naber D, Jones BD, Barnes TR. An open trial of the D1 antagonist SCH 39166 in six cases of acute psychotic states. Psychopharmacology (Berl) 1995;121:323-7.
216. Den Boer JA, van Megen HJ, Fleischhacker WW, et al. Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. Psychopharmacology (Berl) 1995;121:317-22.
217. Karlsson P, Smith L, Farde L, Harnryd C, Sedvall G, Wiesel FA. Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients. Psychopharmacology (Berl) 1995;121:309-16.
218. Tauscher J, Hussain T, Agid O, et al. Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics. Am J Psychiatry 2004;161:1620-5.
219. Goldman-Rakic PS, Selemon LD. Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr Bull 1997;23:437-58.
220. Goldman-Rakic PS, Muly EC 3rd, Williams GV. D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev 2000;31:295-301.
221. Goldman-Rakic PS. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry 1999;46:650-61.
222. Chou YH, Halldin C, Farde L. Clozapine binds preferentially to cortical D1-like dopamine receptors in the primate brain: a PET study. Psychopharmacology (Berl) 2006;185:29-35.
223. Schotte A, Janssen PF, Gommeren W, et al. Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl) 1996;124:57-73.
224. Lidow MS, Goldman-Rakic PS, Gallager DW, Geschwind DH, Rakic P. Distribution of major neurotransmitter receptors in the motor and somatosensory cortex of the rhesus monkey. Neuroscience 1989;32:609-27.
225. Meltzer HY, Li Z, Kaneda Y, Ichikawa J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:1159-72.
226. Meltzer HY. The role of serotonin in antipsychotic drug action. Neuropsychopharmacology 1999;21:106S-15S.
227. Schmidt AW, Lebel LA, Howard HR, Jr., Zorn SH. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol 2001;425:197-201.
228. Trichard C, Paillere-Martinot ML, Attar-Levy D, Recassens C, Monnet F, Martinot JL. Binding of antipsychotic drugs to cortical 5-HT2A receptors: a PET study of chlorpromazine, clozapine, and amisulpride in schizophrenic patients. Am J Psychiatry 1998;155:505-8.
229. Nyberg S, Eriksson B, Oxenstierna G, Halldin C, Farde L. Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenia patients. Am J Psychiatry 1999;156:869-75.
230. Gefvert O, Lundberg T, Wieselgren I, et al. D2 and 5HT2a receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 2001;11:105-10.
231. Kapur S, Zipursky R, Jones C, Shammi C, Remington G, Seeman P. A positron emission tomoghraphy study of quetiapine in schizophrenia. Arch Gen Psychiatry 2000;57:553-9.
232. Mamo D, Kapur S, Shammi CM, et al. A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry 2004;161:818-25.
233. Kapur S, Zipursky R, Remington G, Jones C, McKay G, Houle S. PET evidence that loxapine is an equipotent blocker of 5-HT2 and D2 receptors: implications for the therapeutics of schizophrenia. Am J Psychiatry 1997;154:1525-9.
234. Singh AN, Barlas C, Singh S, Franks P, Mishra RK. A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes. J Psychiatry Neurosci 1996;21:29-35.
235. Nyberg S, Farde L, Eriksson L, Halldin C, Eriksson B. 5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone. Psychopharmacology 1993;110:265-72.
236. Kapur S, Remington G, Zipursky RB, Wilson AA, Houle S. The D2 dopamine receptor occupancy of risperidone and its relationship to extrapyramidal symptoms: a PET study. Life Sci 1995;57:PL103-7.
237. Knable MB, Heinz A, Raedler T, Weinberger DR. Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Psychiat Res Neuroimag 1997;75:91-101.
238. Kuroki T, Meltzer HY, Ichikawa J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther 1999;288:774-81.
239. Sumiyoshi T, Matsui M, Nohara S, et al. Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry 2001;158:1722-5.
240. Sumiyoshi T, Matsui M, Yamashita I, et al. The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia. Biol Psychiatry 2001;49:861-8.
241. Goff DC, Midha KK, Brotman AW, McCormick S, Waites M, Amico ET. An open trial of buspirone added to neuroleptics in schizophrenic patients. J Clin Psychopharmacol 1991;11:193-7.
242. Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT(1A) receptor. Eur J Pharmacol 2002;441:137-40.
243. Newman-Tancredi A, Gavaudan S, Conte C, et al. Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol 1998;355:245-56.
244. Frankle W, Lombardo I, Kegeles L, et al. Occupancy of ziprasidone at the 5-HT1a receptor in patients with schizophrenia measured using [11C]WAY-100635. In: Proceedings of the Annual Meeting of the Society of Nuclear Medicine, Toronto, June 2005.
245. Bantick RA, Montgomery AJ, Bench CJ, et al. A positron emission tomography study of the 5-HT1A receptor in schizophrenia and during clozapine treatment. J Psychopharmacol 2004;18:346-54.
246. Andree B, Hedman A, Thorberg SO, Nilsson D, Halldin C, Farde L. Positron emission tomographic analysis of dosedependent NAD-299 binding to 5-hydroxytryptamine-1A receptors in the human brain. Psychopharmacology (Berl) 2003;167:37-45.
247. Martinez D, Hwang D, Mawlawi O, et al. Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol. A dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans. Neuropsychopharmacology 2001;24:209-29.
248. Bantick RA, Rabiner EA, Hirani E, de Vries MH, Hume SP, Grasby PM. Occupancy of agonist drugs at the 5-HT1A receptor. Neuropsychopharmacology 2004;29:847-59.
249. Kumar JS, Majo VJ, Hsiung SC, et al. Synthesis and in vivo validation of [O-methyl-11C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin- 1-yl]butyl}-4-methyl- 2H-[1,2,4]triazine-3,5-dione: a novel 5-HT1A receptor agonist positron emission tomography ligand. J Med Chem 2006;49:125-34.
250. Prabhakaran J, Parsey RV, Majo VJ, et al. Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4- methyl-2H-[1,2,4]-triazi ne-3,5-dione: a novel agonist 5-HT1A receptor PET ligand. Bioorg Med Chem Lett 2006;16:2101-4.
251. Narendran R, Hwang DR, Slifstein M, et al. In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (-)-N-[11C]propylnorapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride. Synapse 2004;52:188-208.
252. Dougherty D, Alpert N, Rauch S, Fischman A, eds. In vivo neuroreceptor imaging techniques in psychiatric drug development. Washington, DC: American Psychiatric Publishing, 2001.
253. Glazer WM, Kane JM. Depot neuroleptic therapy: an underutilized treatment option. J Clin Psychiatry 1992;53:426-33.
254. Johnson DA. Observations on the use of long-acting depot neuroleptic injections in the maintenance therapy of schizophrenia. J Clin Psychiatry 1984;45:13-21.
255. Gefvert O, Eriksson B, Persson P, et al. Pharmacokinetics and D2 receptor occupancy of long-acting injectable risperidone (Risperdal Consta) in patients with schizophrenia. Int J Neuropsychopharmacol 2005;8:27-36.
256. Remington G, Mamo D, Labelle A, et al. A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone. Am J Psychiatry 2006;163:396-401.
257. Carlsson A, Waters N, Carlsson ML. Neurotransmitter interactions in schizophrenia - therapeutic implications. Biol Psychiatry 1999;46:1388-95.
258. Carr DB, Sesack SR. Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons. J Neurosci 2000;20:3864-73.
259. Karreman M, Moghaddam B. The prefrontal cortex regulates the basal release of dopamine in the limbic striatum: an effect mediated by ventral tegmental area. J Neurochem 1996;66:589-98.
260. Goff DC, Coyle JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 2001;158:1367-77.
261. Goff DC, Tsai G, Levitt J, et al. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999;56:21-7.
262. van Berckel BN, Kegeles LS, Waterhouse R, et al. Modulation of amphetamine-induced dopamine release by group II metabotropic glutamate receptor agonist LY354740 in non-human primates studied with positron emission tomography. Neuropsychopharmacology 2006;31:967-77.
263. Schoepp DD. New directions in the treatment of schizophrenia: modulators of mGlu2 and/or mGlu3 receptors. In: Proceedings of the Annual Meeting of the American College of Neuropsychopharmacology, Hollywood, FL, December 2006.
264. Moghaddam B, Adams BW. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 1998;281:1349-52.
265. Tsukada H, Harada N, Ohba H, Nishiyama S, Kakiuchi T. Facilitation of dopaminergic neural transmission does not affect [11C]SCH23390 binding to the striatal D1 dopamine receptors, but the facilitation enhances phosphodiesterase type-IV activity through D1 receptors: PET studies in the conscious monkey brain. Synapse 2001;42:258-65.