Neuroimaging Findings in Schizophrenia: From Mental to Neuronal Fragmentation

Handbook of Medical Psychiatry

Volumn , Issue , 2003, Pages 237-258

  Kegeles, Lawrence S ^a   Laruelle, Marc ^a  

^a Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85031140248     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.3109/9780203912485-21     Document Type: Chapter

References (202)

1. Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 1976; 2(7992):924– 926.
2. Andreasen NC, Swayze VW, 2nd, Flaum M, Yates WR, Arndt S, McChesney C. Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Effects of gender, age, and stage of illness. Arch Gen Psychiatry 1990; 47(11):1008– 1015.
3. Raz S, Raz N. Structural brain abnormalities in the major psychoses: a quantitative review of the evidence from computerized imaging. Psychol Bull 1990; 108(1):93–108.
4. Van Horn JD, McManus IC. Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle:brain ratio (VBR). Br J Psychiatry 1992; 160:687–697.
5. Strakowski SM, DelBello MP, Adler C, Cecil DM, Sax KW. Neuroimaging in bipolar disorder. Bipolar Disord 2000; 2(3 Pt 1):148–164.
6. McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, Fischer IA, Shenton ME. MRI anatomy of schizophrenia. Biol Psychiatry 1999; 45(9):1099–1119
7. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET. Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000; 157(1):16–25.
8. Nelson MD, Saykin AJ, Flashman LA, Riordan HJ. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry 1998; 55(5):433–440.
9. Bogerts B, Lieberman JA, Ashtari M, Bilder RM, Degreef G, Lerner G, Johns C, Masiar S. Hippocampus-amygdala volumes and psychopathol ogy in chronic schizophrenia. Biol Psychiatry 1993; 33(4):236–246.
10. Goldberg TE, Torrey EF, Berman KF, Weinberger DR. Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia. Psychiatry Res 1994; 55(1):51–61.
11. Barta PE, Pearlson GD, Powers RE, Richards SS, Tune LE. Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am. J. Psychiatry 1990; 147(11):1457–1462.
12. Flaum M, O’Leary DS, Swayze VW, 2nd, Miller DD, Arndt S, Andreasen NC. Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders. J Psychiatr Res 1995; 29(4):261– 276.
13. Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M. Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl Med 1992; 327(9):604–612.
14. Selemon LD, Rajkowska G, Goldman-Rakic PS. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method. J Comp Neurol 1998; 392(3):402–412.
15. Wible CG, Shenton ME, Hokama H, Kikinis R, Jolesz FA, Metcalf D, McCarley RW. Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study. Arch Gen Psychiatry 1995; 52(4):279–288.
16. Chakos MH, Lieberman JA, Bilder RM, Borenstein M, Lerner G, Bogerts B, Wu HW, Kinon B, Ashtari M. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 1994; 151(10):1430–1436.
17. Ohnuma T, Kimura M, Takahashi T, Iwamoto N, Arai H. A magnetic resonance imaging study in first-episode disorganized-type patients with schizophrenia. Psychiatry Clin Neurosci 1997; 51(1):9–15.
18. Gur RE, Cowell P, Turetsky BI, Gallacher F, Cannon T, Bilker W, Gur RC. A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures. Arch Gen Psychiatry 1998; 55(2):145–152.
19. DeLisi LE, Sakuma M, Tew W, Kushner M, Hoff AL, Grimson R. Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia. Psychiatry Res 1997; 74(3):129–140.
20. Degreef G, Ashtari M, Wu HW, Borenstein M, Geisler S, Lieberman J. Follow up MRI study in first episode schizophrenia. Schizophr Res 1991; 5(3):204–206.
21. Ingvar DH, Franzen G. Abnormalities of cerebral blood flow dstribution in patients with chronic schizophrenia. Acta Psychiatr Scand 1974; 50:425–462.
22. Cohen RM, Semple WE, Gross M, Nordahl TE. From syndrome to illness: delineating the pathophysiology of schizophrenia with PET. Schizophr Bull 1988; 14(2):169–176.
23. Williamson P. Hypofrontality in schizophrenia: a review of the evidence. Can J Psychiatry 1987; 32(5):399–404.
24. Gur RE, Pearlson GD. Neuroimaging in schizophrenia research. Schizophr Bull 1993; 19(2):337–353.
25. Kotrla KJ, Weinberger DR. Brain imaging in schizophrenia. Ann Rev Med 1995; 46:113–122.
26. Chua SE, McKenna PJ. Schizophrenia—a brain disease: a critical review of structural and functional cerebral abnormality in the disorder. Br J Psychiatry 1995; 166(5):563–582.
27. Liddle PF. Functional imaging—schizophrenia. Br Med Bull 1996; 52(3):486–494.
28. Andreasen NC, O’Leary DS, Flaum M, Nopoulos P, Watkins GL, Boles Ponto LL, Hichwa RD. Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuroleptic-naive patients. Lancet 1997; 349(9067):1730–1734.
29. Buchsbaum MS, Hazlett EA. Positron emission tomography studies of abnormal glucose metabolism in schizophrenia. Schizophr Bull 1998; 24(3):343–364.
30. Liddle PF, Friston KJ, Frith CD, Hirsch SR, Jones T, Frackowiak RS. Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry 1992; 160:179–186.
31. Weinberger DR, Berman KF, Zec RF. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry 1986; 43:114–124.
32. Andreasen NC, Rezai K, Alliger R, Swayze VW 2nd, Flaum M, Kirchner P, Cohen G, O’Leary DS. Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry 1992; 49(12):943–958.
33. Frith CD, Friston KJ, Herold S, Silbersweig D, Fletcher P, Cahill C, Dolan RJ, Frackowiak RS, Liddle PF. Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task. Br J Psychiatry 1995; 167(3):343–349.
34. Curtis VA, Bullmore ET, Brammer MJ, Wright IC, Williams SC, Morris RG, Sharma TS, Murray RM, McGuire PK. Attenuated frontal activation during a verbal fluency task in patients with schizophrenia. Am J Psychiatry 1998; 155(8):1056–1063.
35. Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD. Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry 1998; 155(9):1285–1287.
36. Weinberger DR, Berman KF. Prefrontal function in schizophrenia: confounds and controversies. Phil Trans R Soc Lond Ser B. Biol Sci 1996; 351(1346):1495–1503.
37. Friston KJ, Frith CD, Liddle PF, Frackowiak RS. Functional connectivity: the principal-component analysis of large (PET) data sets. J. Cereb. Blood Flow Metab 1993; 13(1):5–14.
38. Braver TS, Cohen JD, Nystrom LE, Jonides J, Smith EE, Noll DC. A parametric study of prefrontal cortex involvement in human working memory. Neuroimage 1997; 5(1):49–62.
39. Barch DM, Braver TS, Nystrom LE, Forman SD, Noll DC, Cohen JD. Dissociating working memory from task difficulty in human prefrontal cortex. Neuropsychologia 1997; 35(10):1373–1380.
40. Manoach DS, Press DZ, Thangaraj V, Searl MM, Goff DC, Halpern E, Saper CB, Warach S. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry 1999; 45(9):1128–1137.
41. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E, Saper CB, Rauch SL. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance [in process citation]. Biol Psychiatry 2000; 48(2):99–109.
42. Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex 2000; 10(11):1078–1092.
43. Wagner H Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom SB, Lukas SE, Kramer AV, Kuhar MJ. Imaging dopamine receptors in the human brain by positron tomography. Science 1983; 221(4617): 1264–1266.
44. Rossum V. The significance of dopamine receptor blockade for the mechanism of action of neuroleptic drugs. Arch Int Pharmacodyn Ther 1966; 160:492–494.
45. Carlsson A, Lindqvist M. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 1963; 20:140–144.
46. Seeman P, Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 1975; 188:1217–1219.
47. Creese I, Burt DR, Snyder SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976; 19:481– 483.
48. Connell PH. Amphetamine Psychosis. London; Chapman and Hall, 1958.
49. Angrist BM, Gershon S. The phenomenology of experimentally induced amphetamine psychosis—preliminary observation. Biol Psychiatry 1970; 2:95–107.
50. Goldman-Rakic PS, Selemon LD. Functional and anatomical aspects of prefrontal pathology in schizophrenia. Schizophr Bull 1997; 23:437–458.
51. Weinberger DR. Implications of the normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44:660–669.
52. Knable MB, Weinberger DR. Dopamine, the prefrontal cortex and schizophrenia. J Psychopharmacol 1997; 11(2):123–131.
53. 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; 156(10):1580–1589.
54. Deutch AY. Prefrontal cortical dopamine systems and the elaboration of functional corticostriatal circuits: implications for schizophrenia and Parkinson’s disease. J Neural Transm Gen Sect 1993; 91(2–3):197– 221.
55. Wilkinson LS. The nature of interactions involving prefrontal and striatal dopamine systems. J Psychopharmacol 1997; 11(2):143–150.
56. Weinberger DR, Laruelle M. Neurochemical and neuropharmacological imaging in schizophrenia. In Neuropsychopharmacology—the fifth generation of progress. Davis KL, Charney DS, Coyle JT, Nemeroff C, eds. Lippincott, New York; Williams and Wilkins, 2001.
57. Wong DF, Wagner HN, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JK, Malat J, Williams JA, O’Tuama LA, Snyder SH, Kuhar MJ, Gjedde A. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 1986; 234:1558–1563.
58. Crawley JC, Owens DG, Crow TJ, Poulter M, Johnstone EC, Smith T, Oldland SR, Veall N, Owen F, Zanelli GD. Dopamine D2 receptors in schizophrenia studied in vivo. Lancet 1986; 2(8500):224–225.
59. Blin J, Baron JC, Cambon H, Bonnet AM, Dubois B, Loc’h C, Maziere B, Agid Y. Striatal dopamine D2 receptors in tardive dyskinesia. PET study. J Neurol Neurosurg Psychiatry 1989; 52(11):1248–1252.
60. Martinot J-L, Peron-Magnan P, Huret J-D, Mazoyer B, Baron J-C, Boulenger J-P, Caillard V, Syrota A. Striatal D2 dopaminergic receptors assessed with positron emission tomography and 76-Br-bromospiperone in untreated patients. Am J Psychiatry 1990; 147:346– 350.
61. Tune LE, Wong DF, Pearlson G, Strauss M, Young T, Shaya EK, Dannals RF, Wilson AA, Ravert HT, Sapp J. Dopamine D2 receptor density estimates in schizophrenia: a positron emission tomography study with 11C-N-methylspiperone. Psychiatry Res 1993; 49(3):219–237.
62. Nordstrom AL, Farde L, Eriksson L, Halldin C. No elevated D2 dopamine receptors in neuroleptic-naïve schizophrenic patients revealed by positron emission tomography and [11C]N-methylspiperone [see comments]. Psychiatry Res 1995; 61(2):67–83.
63. Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M. Tateno Y, Toru M. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997; 385(6617):634–636.
64. Farde L, Wiesel F, Stone-Elander S, Halldin C, Nordsro¨m AL, Hall H, Sedvall G. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 1990; 47:213– 219.
65. Hietala J, Syva¨lahti E, Vuorio K, Nagren K, Lehikoinen P, Ruotsalainen U,. Ra¨kko¨la¨inen V, Lehtinen V, Wegelius U. Striatal D2 receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography. Arch Gen Psychiatry 1994; 51:116–123.
66. 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.
67. Laruelle M, Abi-Dargham A, Van Dyck CH, Gil R, De Souza CD, Erdos J, McCance 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.
68. Knable MB, Egan MF, Heinz A, Gorey J, Lee KS, Coppola R, Weinberger DR. Altered dopaminergic function and negative symptoms in drug-free patients with schizophrenia. [123I]-iodobenzamide SPECT study. Br J Psychiatry 1997; 171:574–577.
69. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, deBartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D. Schizophrenia is associated with elevated amphetamineinduced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 1997; 94(6):2569–2574.
70. Abi-Dargham A, Gil R, Krystal J, Baldwin R, Seibyl J, Bowers M, Van Dyck C, Charney D, Innis R, Laruelle M. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 1998; 155:761–767.
71. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles L, Weiss R, Cooper T, Mann JJ, Van Heertum R, Gorman J, Laruelle M. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 2000; 97(14):8104–8109.
72. Martinot Jl, Paille`re-Martinot ML, Loc’h C, Hardy P, Poirier MF, Mazoyer B, Beaufils B, Mazie`re B, Alliaire JF, Syrota A. The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry 1991; 158:346–350.
73. Martinot JL, Paille`re-Martinot ML, Loch’H C, Lecrubier Y, Dao-Castellana MH, Aubin F, Allilaire JF, Mazoyer B, Mazie`re B, Syrota A. Central D2 receptors and negative symptoms of schizophrenia. Br J Pharmacol. 1994; 164:27–34.
74. Seeman P, Guan H-C, Niznik HB. Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3 H]raclopride: implications for positron emission tomography of the human brain. Synapse 1989; 3:96–97.
75. Seeman P. Brain dopamine receptors in schizophrenia. PET problems. Arch Gen Psychiatry 1988; 45:598–560.
76. Reith J, Benkelfat C, Sherwin A, Yasuhara Y, Kuwabara H, Andermann F, Bachneff S, Cumming P, Diksic M, Dyve SE, Etienne P, Evans AC, Lal S, Shevell M, Savard G, Wong DF, Chouinard G, Gjedde A. Elevated dopa decarboxylase activity in living brain of patients with psychosis. Proc Natl Acad Sci USA 1994; 91:11651–11654.
77. Hietala J, Syvalahti E, Vuorio K, Rakkolainen V, Bergman J, Haaparanta M, Solin O, Kuoppamaki M, Kirvela O, Ruotsalainen U. Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients. Lancet 1995; 346(8983):1130–1131.
78. Dao-Castellana MH, Paillere-Martinot ML, Hantraye P, Attar-Levy D, Remy P, Crouzel C, Artiges E, Feline A, Syrota A, Martinot JL. Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophr Res 1997;23(2):167–174.
79. Hietala J, Syvalahti E, Vilkman H, Vuorio K, Rakkolainen V, Bergman J, Haaparanta M, Solin O, Kuoppamaki M, Eronen E, Ruotsalainen U, Salokangas RK. Depressive symptoms and presynaptic dopamine function in neurolepticnaive schizophrenia. Schizophr Res 1999; 35(1):41– 50.
80. Lindstrom LH, Gefvert O, Hagberg G, Lundberg T, Bergstrom M, Hartvig P, Langstrom B. Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(beta-11C) DOPA and PET. Biol Psychiatry 1999; 46(5):681–688.
81. Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000; 20(3):423– 451.
82. Villemagne VL, Wong DF, Yokoi F, Stephane M, Rice KC, Matecka D, Clough DJ, Dannals RF, Rothman RB. GBR12909 attenuates amphetamineinduced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans. Synapse 1999; 33(4):268–273.
83. Laruelle M, Iyer RN, Al-Tikriti MS, Zea-Ponce Y, Malison R, Zoghbi SS, Baldwin RM, Kung HF, Charney DS, Hoffer PB, Innis RB, Bradberry CW. Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 1997; 25:1–14.
84. Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R. Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 1999; 46(1):56–72.
85. Hwang D, Kegeles LS, Laruelle M. (-)-N-[(11)C] propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors. Nucl Med Biol 2000; 27(6):533–539.
86. 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(2):125–132.
87. Kegeles LS, Abi-Dargham A, Zea-Ponce Y, Rodenhiser-Hill J, Mann JJ, Van Heertum RL, Cooper TB, Carlsson A, Laruelle M. Modulation of amphetamine-induced striatal dopamine release by ketamine in humans: implications for schizophrenia. Biol Psychiatry 2000; 48(7):627–640.
88. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991; 148(10):1301–1308.
89. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 1995; 52(12):998–1007.
90. Moghaddam B. Recent basic findings in support of excitatory amino acid hypotheses of schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 1994; 18(5):859–870.
91. Laruelle M, D’Souza CD, Baldwin RM, AbiDargham A, Kanes SJ, Fingado CL, Seibyl JP, Zoghbi SS, Bowers MB, Jatlow P, Charney DS, Innis RB. Imaging D-2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology 1997; 17(3):162–174.
92. Fujita M, Verhoeff NP, Varrone A, Zoghbi SS, Baldwin RM, Jatlow PA, Anderson GM, Seibyl JP, Innis RB. Imaging extrastriatal dopamine D (2) receptor occupancy by endogenous dopamine in healthy humans. Eur J Pharmacol 2000; 387(2):179– 188.
93. Laruelle M, Abi-Dargham A, Van Dyck C, Gil R, D’Souza CD, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [(123)I]beta-CIT. Biol Psychiatry 2000; 47(5):371–379.
94. Hirai M, Kitamura N, Hashimoto T, Nakai T, Mita T, Shirakawa O, Yamadori T, Amano T, NoguchiKuno SA, Tanaka C. [3 H]GBR-12935 binding sites in human striatal membranes: binding characteristics and changes in parkinsonians and schizophrenics. Jpn J Pharmacol 1988; 47(3):237–243.
95. Czudek C, Reynolds GP. [3 H]GBR 12935 binding to the dopamine uptake site in post-mortem brain tissue in schizophrenia. J Neural Transm 1989; 77(2–3):227– 230.
96. Pearce RK, Seeman P, Jellinger K, Tourtellotte WW. Dopamine uptake sites and dopamine receptors in Parkinson’s disease and schizophrenia. Eur Neurol 1990; 30(suppl 1):9–14.
97. 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(5):546–557.
98. Chinaglia G, Alvarez FJ, Probst A, Palacios JM. Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson’s disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3 H]mazindol. Neuroscience 1992; 49(2):317–327.
99. Knable MB, Hyde TM, Herman MM, Carter JM, Bigelow L, Kleinman JE. Quantitative autoradiography of dopamine-D1 receptors, D2 receptors, and dopamine uptake sites in postmortem striatal specimens from schizophrenic patients. Biol Psychiatry 1994; 36(12):827–835.
100. De Keyser J, Ebinger G, Vauquelin G. Evidence for a widespread dopaminergic innervation of the human cerebral neocortex. Neurosci Lett 1989; 104:281–285.
101. 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; 11:245–256.
102. Laruelle M, Casanova M, Weinberger D, Kleinman J. Postmortem study of the dopaminergic D1 receptors in the dorsolateral prefrontal cortex of schizophrenics and controls. Schizophrenia Res 1990; 3:30–31.
103. Knable MB, Hyde TM, Murray AM, Herman MM, Kleinman JE. A postmortem study of frontal cortical dopamine D1 receptors in schizophrenics, psychiatric controls, and normal controls. Biol Psychiatry 1996; 40(12):1191–1199.
104. Meador-Woodruff JH, Haroutunian V, Powchik P, Davidson M, Davis KL, Watson SJ. Dopamine receptor transcript expression in striatum and prefrontal and occipital cortex. Focal abnormalities in orbitofrontal cortex in schizophrenia. Arch Gen Psychiatry 1997; 54(12):1089–1095.
105. Abi-Dargham A, Gil R, Mawlawi O, Hwang DR, Kochan L, Lombardo I, Rodenhiser J, Kegeles L, Martinez D, Keilp J, Van Heertum R, Gorman J, Laruelle M. Selective alteration in D1 receptors in schizophrenia: a PET in vivo study. J Nucl Med 2001; 42:17P.
106. Lewis DA. GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Rev 2000; 31(2–3):270–276.
107. Benes FM. Emerging principles of altered neural circuitry in schizophrenia. Brain Res Rev 2000; 31(2– 3):251–269.
108. Busatto GF, Pilowsky LS, Costa DC, Ell PJ, David AS, Lucey JV, Kerwin RW. Correlation between reduced in vivo benzodiazepine receptor binding and severity of psychotic symptoms in schizophrenia. Am J Psychiatry 1997; 154(1):56–63.
109. Verhoeff NP, Soares JC, D’Souza CD, Gil R, Degen K, Abi-Dargham A, Zoghbi SS, Fujita M, Rajeevan N, Seibyl JP, Krystal JH, Van Dyck CH, Charney DS, Innis RB. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Res 1999; 91(3):163–173.
110. Abi-Dargham A, Laruelle M, Krystal J, D’Souza C, Zoghbi S, Baldwin RM, Seibyl J, Mawlawi O, de Erasquin G, Charney D, Innis RB. No evidence of altered in vivo benzodiazepine receptor binding in schizophrenia. Neuropsychopharmacology 1999; 20(6):650–661.
111. Schro¨ der J, Bubeck B, Demisch S, Sauer H. Benzodiazepine receptor distribution and diazepam binding in schizophrenia: an exploratory study. Psychiat. Res. Neuroimaging 1997; 68(2–3):125–131.
112. Ball S, Busatto GF, David AS, Jones SH, Hemsley DR, Pilowsky LS, Costa DC, Ell PJ, Kerwin RW. Cognitive functioning and GABAA/benzodiazepine receptor binding in schizophrenia: a 123I-iomazenil SPET study. Biol Psychiatry 1998; 43(2):107–117.
113. Benes FM, Wickramasinghe R, Vincent SL, Khan Y, odtenkopf M. Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain. Brain Res 1997; 755(1):121–129.
114. Abi-Dargham A, Krystal J. Serotonin receptors as target of antipsychotic medications. In: Neurotransmitter Receptors in Actions of Antipsychotic Medications. Lidow MS, ed. Boca Raton, FL; CRC Press LLC, 2000, pp 79–107.
115. Lewis R, Kapur S, Jones C, DaSilva J, Brown GM, Wilson AA, Houle S, Zipursky RB. Serotonin 5-HT2 receptors in schizophrenia: a PET study using [18F]setoperone in neuroleptic-naive patients and normal subjects. Am J Psychiatry 1999; 156(1):72–78.
116. 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(1):13–17.
117. Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M. Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography. Life Sci 2000; 66(25):2455–2464.
118. 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(6):1016–1018.
119. 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(2):286– 293.
120. 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–S20.
121. Farde L, Nordstro¨ m 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; 49:538–544.
122. Wolkin A, Barouche F, Wolf AP, Rotrosen J, Fowler JS, Shiue CY, Cooper TB, Brodie JD. Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry 1989; 146(7):905–908.
123. 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.
124. Nordstrom AL, Farde L, Wiesel FA, Forslund K, Pauli S, Halldin C, Uppfeldt G. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients. Biol Psychiatry 1993; 33(4):227–235.
125. 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(4):514–520.
126. 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 [see comments]. Am J Psychiatry 1995; 152(10): 1444–1449.
127. 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; 110:265–272.
128. 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(10):L103– L107.
129. Knable MB, Heinz A, Raedler T, Weinberger DR. Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Psychiatr Res Neuroimag 1997; 75(2):91–101.
130. Kapur S, Zipursky RB, Remington G, Jones C, DaSilva J, Wilson AA, Houle S. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 1998; 155(7):921–928.
131. 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(2):119–126.
132. 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(6):553–559.
133. Pilowsky LS, Mulligan RS, Acton PD, Ell PJ, Costa DC, Kerwin RW. Limbic selectivity of clozapine. Lancet 1997; 350(9076):490–491.
134. Farde L, Suhara T, Nyberg S, Karlsson P, Nakashima Y, Hietala J, Halldin C. 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(4):396–404.
135. Bigliani V, Mulligan RS, Acton PD, Visvikis D, Ell PJ, Stephenson C, Kerwin RW, Pilowsky LS. 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; 175:231–238.
136. Abi-Dargham A, Hwang DR, Huang Y, Zea-Ponce Y, Martinez D, Lombardo I, Broft A, Hashimoto T, Slifstein M, Mawlawi O, Van Heertum R, Laruelle M. Reliable quantification of both striatal and extrastriatal D2 receptors in humans with [18F]fallypride. J Nucl Med 2000; 41:139P.
137. Mukherjee J, Christian BT, Narayanan TK, Shi B, Mantil J. Measurement of striatal and extrastriatal D-2 receptor occupancy by clozapine and risperidone using [18F]fallypride and PET. Neuroimage 2000; 11:S53.
138. 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(2):1058–1066.
139. 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; 3:332–341.
140. Martinez D, Hwang DR, Broft A, Mawlawi O, Simpson N, Ngo K, Pidcock J, Van Heertum R, Laruelle M. PET imaging of amphetamine-induced endogenous dopamine release in mesolimbic and nigro-striatal dopamine systems in humans. J Nucl Med 2000; 41:105P.
141. Drevets WC, Price JC, Kupfer DJ, Kinahan PE, Lopresti B, Holt D, Mathis C. PET measures of amphetamine-induced dopamine release in ventral versus dorsal striatum. Neuropsychopharmacology 1999; 21(6):694–709.
142. Wolkin A, Brodie JD, Barouche F, Rotrosen J, Wolf AP, Smith M, Fowler J, Cooper TB. Dopamine receptor occupancy and plasma haloperidol levels. Arch Gen Psychiatry 1989; 46(5):482–484.
143. Fitzgerald PB, Kapur S, Remington G, Roy P, Zipursky RB. Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels. Psychopharmacology (Berl) 2000; 149(1):1–5.
144. Hagberg G, Gefvert O, Bergstrom M, Wieselgren IM, Lindstrom L, Wiesel FA, Langstrom B. N-[11C]methylspiperone PET, in contrast to [11C]raclopride, fails to detect D2 receptor occupancy by an atypical neuroleptic. Psychiatry Res 1998; 82(3):147–160.
145. Nasrallah HA, Skinner TE, Schmalbrock P, Robitaille PM. In vivo 1H-NMR-spectroscopy of the limbic temporal lobe in patients with schizophrenia. In: NMR Spectroscopy in Psychiatric Brain Disorders. Nasrallah HA, Pettegrew JW, eds. Washington, D C, American Psychiatric Press, 1995, pp 1–20.
146. Gupta RK, Gupta P, Moore RD. NMR studies of intracellular metal ions in intact cells and tissues. Annu Rev Biophys Bioeng 1984; 13:221–246.
147. Pettegrew JW, Withers G, Panchalingam K, Post JF. Considerations for brain pH assessment by 31P NMR. Magn Reson Imag 1988; 6(2):135–142.
148. Murphy EJ, Rajagopalan B, Brindle KM, Radda GK. Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med 1989; 12(2):282–289.
149. Pettegrew JW, Keshavan MS, Panchalingam K, Strychor S, Kaplan DB, Tretta MG, Allen M. Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drugnaive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy [see comments]. Arch Gen Psychiatry 1991; 48(6):563–568.
150. Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res 1982; 17(4):319–334.
151. Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, Van Kammen DP, King AC, Johnson JL, Manning RG, Flynn RW, Mann LS, Bunney WE Jr, Sokoloff L. Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia. Arch Gen Psychiatry 1982; 39(3):251–259.
152. Andreasen NC, Rezai K, Alliger R, Swayze VW 2nd, Flaum M, Kirchner P, Cohen G, O’Leary DS. Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon-133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry 1992; 49(12):943–958.
153. Stanley JA, Williamson PC, Drost DJ, Carr TJ, Rylett RJ, Malla A, Thompson RT. An in vivo study of the prefrontal cortex of schizophrenic patients at different stages of illness via phosphorus magnetic resonance spectroscopy. Arch Gen Psychiatry 1995; 52(5):399– 406.
154. Williamson P, Drost D, Stanley J, Carr T, Morrison S, Merskey H. Localized phosphorus-31 magnetic resonance spectroscopy in chronic schizophrenic patients and normal controls. Arch Gen Psychiatry 1991; 48(6):578.
155. Kato T, Shioiri T, Murashita J, Hamakawa H, Inubushi T, Takahashi S. Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia. Psychiatry Res 1995; 61(3): 151–160.
156. Potwarka JJ, Drost DJ, Williamson PC, Carr T, Canaran G, Rylett WJ, Neufeld RW. A 1H-decoupled 31P chemical shift imaging study of medicated schizophrenic patients and healthy controls. Biol Psychiatry 1999; 45(6):687–693.
157. Shioiri T, Kato T, Inubushi T, Murashita J, Takahashi S. Correlations of phosphomonoesters measured by phosphorus-31 magnetic resonance spectroscopy in the frontal lobes and negative symptoms in schizophrenia. Psychiatry Res 1994; 55(4):223–235.
158. Volz HP, Rzanny R, Rossger G, Hubner G, Kreitschmann-Andermahr I, Kaiser WA, Sauer H. Decreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31Pmagneto-resonance spectroscopic study. Psychiatry Res 1997; 76(2–3):123–129.
159. Deicken RF, Calabrese G, Merrin EL, Meyerhoff DJ, Dillon WP, Weiner MW, Fein G. 31Phosphorus magnetic resonance spectroscopy of the frontal and parietal lobes in chronic schizophrenia. Biol Psychiatry 1994; 36(8):503–510.
160. Fujimoto T, Nakano T, Takano T, Hokazono Y, Asakura T, Tsuji T. Study of chronic schizophrenics using 31P magnetic resonance chemical shift imaging. Acta Psychiatr Scand 1992; 86(6):455–462.
161. Kegeles LS, Humaran TJ, Mann JJ. In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy. Biol Psychiatry 1998; 44:382–398.
162. Keshavan MS, Stanley JA, Pettegrew JW. Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings—part II. Biol Psychiatry 2000; 48(5):369–380.
163. O’Callaghan E, Redmond O, Ennis R, Stack J, Kinsella A, Ennis JT, Larkin C, Waddington JL. Initial investigation of the left temporoparietal region in schizophrenia by 31P magnetic resonance spectroscopy. Biol Psychiatry 1991; 29(11):1149–1152.
164. Fukuzako H, Takeuchi K, Ueyama K, Fukuzako T, Hokazono Y, Hirakawa K, Yamada K, Hashiguchi T, Takigawa M, Fujimoto T. 31P magnetic resonance spectroscopy of the medial temporal lobe of schizophrenic patients with neuroleptic-resistant marked positive symptoms. Eur Arch Psychiatry Clin Neurosci 1994; 244(5):236–240.
165. Fukuzako H, Fukuzako T, Hashiguchi T, Kodama S, Takigawa M, Fujimoto T. Changes in levels of phosphorus metabolites in temporal lobes of drug-naïve schizophrenic patients. Am J Psychiatry 1999; 156(8):1205–1208.
166. Calabrese G, Deicken RF, Fein G, Merrin EL, Schoenfeld F, Weiner MW. 31Phosphorus magnetic resonance spectroscopy of the temporal lobes in schizophrenia. Biol Psychiatry 1992; 32(1):26–32.
167. Deicken RF, Calabrese G, Merrin EL, Vinogradov S, Fein G, Weiner MW. Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: a 31phosphorous magnetic resonance spectroscopic imaging study. Biol Psychiatry 1995; 38(5):279–286.
168. Frahm J, Merboldt KD, Hanicke W. Localized proton spectroscopy using stimulated echoes. J Magn Reson Imaging 1987; 72:502–508.
169. Urenjak J, Williams SR, Gadian DG, Noble M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 1993; 13:981–989.
170. Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience 1991; 45:37–45.
171. DeStefano N, Francis G, Antel JP, Arnold DL. Reversible decreases of N-acetylaspartate in the brain of patients with relapsing remitting multiple sclerosis. Proc Soc Magn Res Med 1993; 1:280.
172. Tsai G, Coyle JT. N-Acetylaspartate in neuropsychiatric disorders. Prog Neurobiol 1995; 46:531–540.
173. Maier M. In vivo magnetic resonance spectroscopy. Applications in psychiatry. Br J Psychiatry 1995; 167(3):299–306.
174. Behar KL, Rothman DL, Spencer DD, Petroff OA. Analysis of macromolecule resonances in 1H NMR spectra of human brain. Magn Reson Med 1994; 32(3):294–302.
175. Hwang JH, Graham GD, Behar KL, Alger JR, Prichard JW, Rothman DL. Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain. Magn Reson Med 1996; 35(5):633–639.
176. Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci USA 1993; 90(12):5662–5666.
177. Keltner JR, Wald LL, Christensen JD, Maas LC, Moore CM, Cohen BM, Renshaw PF. A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses. Magn Reson Med 1996; 36:458–461.
178. Mason GF, Pan JW, Ponder SL, Twieg DB, Pohost GM, Hetherington HP. Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T. Magn Reson Med 1994; 32(1):142–145.
179. Stanley JA, Williamson PC, Drost DJ, Rylett RJ, Carr TJ, Malla A, Thompson RT. An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients. Schizophr Bull 1996; 22(4):597–609.
180. Bartha R, al-Semaan YM, Williamson PC, Drost DJ, Malla AK, Carr TJ, Densmore M, Canaran G, Neufeld RW. A short echo proton magnetic resonance spectroscopy study of the left mesial-temporal lobe in first-onset schizophrenic patients. Biol Psychiatry 1999; 45(11):1403–1411.
181. Cecil KM, Lenkinski RE, Gur RE, Gur RC. Proton magnetic resonance spectroscopy in the frontal and temporal lobes of neuroleptic naive patients with schizophrenia. Neuropsychopharmacology 1999; 20(2):131–140.
182. Choe BY, Suh TS, Shinn KS, Lee CW, Lee C, Paik IH. Observation of metabolic changes in chronic schizophrenia after neuroleptic treatment by in vivo hydrogen magnetic resonance spectroscopy. Invest Radiol 1996; 31(6):345–352.
183. Bertolino A, Nawroz S, Mattay VS, Barnett AS, Duyn JH, Moonen CTW, Frank JA, Tedeschi G, Weinberger DR. Regionally specific pattern of neurochemical pathology in schizophrenia as assessed by multislice proton magnetic resonance spectroscopic imaging. Am J Psychiatry 1996; 153:1554–1563.
184. Bertolino A, Callicott JH, Elman I, Mattay VS, Tedeschi G, Frank JA, Breier A, Weinberger DR. Regionally specific neuronal pathology in untreated patients with schizophrenia: a proton magnetic resonance spectroscopic imaging study. Biol Psychiatry 1998; 43(9):641–648.
185. Deicken RF, Zhou L, Corwin F, Vinogradov S, Weiner MW. Decreased left frontal lobe N-acetylaspartate in schizophrenia. Am J Psychiatry 1997; 154(5):688–690.
186. Buckley PF, Moore C, Long H, Larkin C, Thompson P, Mulvany F, Redmond O, Stack JP, Ennis JT, Waddington JL. 1H-Magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates. Biol Psychiatry 1994; 36(12):792–800.
187. Fukuzako H, Takeuchi K, Hokazono Y, Fukuzako T, Yamada K, Hashiguchi T, Obo Y, Ueyama K, Takigawa M, Fujimoto T. Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report. Psychiatry Res 1995; 61(4):193–200.
188. Callicott JH, Egan MF, Bertolino A, Mattay VS, Langheim FJ, Frank JA, Weinberger DR. Hippocampal N-acetyl aspartate in unaffected siblings of patients with schizophrenia: a possible intermediate neurobiological phenotype. Biol Psychiatry 1998; 44(10):941–950.
189. Choe BY, Kim KT, Suh TS, Lee C, Paik IH, Bahk YW, Shinn KS, Lenkinski RE. 1H Magnetic resonance spectroscopy characterization of neuronal dysfunction in drug-naive, chronic schizophrenia. Acad Radiol 1994; 1:211–216.
190. Deicken RF, Zhou L, Schuff N, Fein G, Weiner MW. Hippocampal neuronal dysfunction in schizophrenia as measured by proton magnetic resonance spectroscopy. Biol Psychiatry 1998; 43(7):483–488.
191. Lim KO, Adalsteinsson E, Spielman D, Sullivan EV, Rosenbloom MJ, Pfefferbaum A. Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia. Arch Gen Psychiatry 1998; 55(4):346–352.
192. Maier M, Ron MA, Barker GJ, Tofts PS. Proton magnetic resonance spectroscopy: an in vivo method of estimating hippocampal neuronal depletion in schizophrenia. Psychol Med 1995; 25(6):1201–1209.
193. Nasrallah HA, Skinner TE, Schmalbrock P, Robitaille PM. Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study. Br J Psychiatry 1994; 165(4):481–485.
194. Yurgelun-Todd DA, Renshaw PF, Gruber SA, Waternaux C, Cohen BM. Proton magnetic resonance spectroscopy of the temporal lobes in schizophrenics and normal controls. Schizophr Res 1996; 19:55–59.
195. Heimberg C, Komoroski RA, Lawson WB, Cardwell D, Karson CN. Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect. Psychiatry Res 1998; 83(2):105–115.
196. Renshaw PF, Yurgelun-Todd DA, Tohen M, Gruber S, Cohen BM. Temporal lobe proton magnetic resonance spectroscopy of patients with first-episode psychosis. Am J Psychiatry 1995; 152(3):444–446.
197. Keshavan MS, Montrose DM, Pierri JN, Dick EL, Rosenberg D, Talagala L, Sweeney JA. Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies. Prog Neuropsychopharmacol Biol Psychiatry 1997; 21(8):1285–1295.
198. Bertolino A, Esposito G, Callicott JH, Mattay VS, Van Horn JD, Frank JA, Berman KF, Weinberger DR. Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia. Am J sychiatry 2000; 157(1):26–33.
199. Tofts PS, Wray S. A critical assessment of methods of measuring metabolite concentrations by NMR spectroscopy. NMR Biomed 1988; 1:1–10.
200. Shungu DC, Bhujwalla ZM, Li SJ, Rose LM, Wehrle JP, Glickson JD. Determination of absolute phosphate metabolite concentration in RIF-1 tumors in vivo by 31P-1H-2H NMR spectroscopy using water as an internal intensity reference. Magn Reson Med 1992; 28:105–121.
201. Rothman DL, Novotny EJ, Shulman GI, Howseman AM, Petroff OA, Mason G, Nixon T, Hanstock CC, Prichard JW, Shulman RG. 1H-[13C] NMR measurements of [4–13C]glutamate turnover in human brain. Proc Natl Acad Sci USA 1992; 89(20):9603–9606.
202. Laakso A, Vilkman H, Alakare B, Haaparanta M, Bergman J, Solin O, Peurasaari J, Rakkolainen V, Syvalahti E, Hietala J. Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography. Am J Psychiatry 2000; 157(2):269–271.