Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia

Cerebral Cortex

Volumn 17, Issue SUPPL. 1, 2007, Pages

  Tan, Hao Yang ^a   Callicott, Joseph H ^a   Weinberger, Daniel R ^a  

^a NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

Dopamine; FMRI; Genetics; Glutamate; Psychosis; Working memory

Indexed keywords

GENETICS; HUMAN; IMAGE PROCESSING; PATHOLOGY; PATHOPHYSIOLOGY; PREFRONTAL CORTEX; PSYCHOLOGY; REVIEW; RISK; SCHIZOPHRENIA; SHORT TERM MEMORY;

HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MEMORY, SHORT-TERM; PREFRONTAL CORTEX; RISK; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY;

EID: 38449120712     PISSN: 10473211     EISSN: 14602199     Source Type: Journal    
DOI: 10.1093/cercor/bhm069     Document Type: Article

References (162)

1. Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR, Kleinman JE. 2003. Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J Neurosci. 23:2008-2013. (Pubitemid 36368887)
2. Andreasen NC, O'Leary DS, Arndt S, Cizadlo T, Rezai K, Watkins GL, Boles Ponto LL, Hichwa RD. 1995. I. PET studies of memory: novel and practiced free recall of complex narratives. Neuro Image. 2:284.
3. Andreasen NC, Rezai K, Alliger R, Swayze II VW, Flaum M, Kirchner P, Cohen G, O'Leary DS. 1992. 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. 49:943.
4. Ang YG, Tan HY. 2004. Academic deterioration prior to first episode schizophrenia in young Singaporean males. Psychiatry Res. 121:303-307.
5. Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, Alce G, Iudicello JE, Akbar N, Egan MF, et al. 2007. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 32:1011-1020 (Pubitemid 46631983)
6. Awh E, Jonides J, Smith EE, Schumacher EH, Koeppe RA, Katz S. 1996. Dissociation of storage and rehearsal in verbal working memory: evidence from positron emission tomography. Psychol Sci. 7:25-31.
7. Baddeley AD. 2003. Working memory: looking back and looking forward. Nat Rev Neurosci. 4:829-839.
8. Badner JA, Gershon ES. 2002. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry. 7:405-411. (Pubitemid 34499362)
9. Barch DM, Carter CS, Braver TS, Sabb FW, MacDonald A, Noll DC, Cohen JD. 2001. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Arch Gen Psychiatry. 58:280-288. (Pubitemid 32209682)
10. Barch DM, Csernansky JG, Conturo T, Snyder AZ. 2002. Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism? J Abnorm Psychol. 111:478-494. (Pubitemid 34791149)
11. Barch DM, Sheline YI, Csernansky JG, Snyder AZ. 2003. Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Biol Psychiatry. 53:376.
12. Berman KF, Doran AR, Pickar D, Weinberger DR. 1993. Is the mechanism of prefrontal hypofunction in depression the same as in schizophrenia? Regional cerebral blood flow during cognitive activation. Br J Psychiatry. 162:183-192. (Pubitemid 23041394)
13. Bertolino A, Caforio G, Blasi G, Candia MD, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott JH, et al. 2004. Interaction of COMT Val108/158 met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry. 161:1798-1805. (Pubitemid 39314673)
14. Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates JA, Pappadopulos E, Willson DF, Alvir J M J, Woerner MG, et al. 2000. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry. 157:549-559. (Pubitemid 30191193)
15. Blasi G, Mattay VS, Alessandro B, Elvevag B, Callicott JH, Das S, Kolachana B, Egan MF, Goldberg TE, Weinberger DR. 2005. Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci. 25:5038-5045. (Pubitemid 40712847)
16. Braver TS, Barch DM, Cohen JD. 1999. Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function. Biol Psychiatry. 46:312.
17. Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R, Goldberg TE, Weinberger DR. 2000. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex. 10:1078-1092.
18. Callicott JH, Egan MF, Mattay VS, Bertolino A, Bone AD, Verchinksi B, Weinberger DR. 2003. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry. 160:709-719. (Pubitemid 41079604)
19. Callicott JH, Mattay VS, Bertolino A, Finn K, Coppola R, Frank JA, Goldberg TE, Weinberger DR. 1999. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex. 9:20-26. (Pubitemid 29062016)
20. Callicott JH, Mattay VS, Verchinski BA, Marenco S, Egan MF, Weinberger DR. 2003. Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am J Psychiatry. 160:2209-2215. (Pubitemid 39619615)
21. Callicott JH, Tallent K, Bertolino A, Knable MB, Coppola R, Goldberg T, Mattay VS, Weinberger DR, Van Gelderen P, Moonen C T W, et al. 1998. Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia. Neuropsychopharmacology. 18:186.
22. Callicott JH, Weinberger DR. 1999. Neuropsychiatric dynamics: the study of mental illness using functional magnetic resonance imaging. Eur J Radiol. 30:95.
23. Cannon M, Caspi A, Moffitt TE, Harrington H, Taylor A, Murray RM, Poulton R. 2002. Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder-results from a longitudinal birth cohort. Arch Gen Psychiatry. 59:449-456. (Pubitemid 34477681)
24. Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML. 2001. Interactions between monoamines, glutamate, and GABA in schizophrenia: new Evidence. Annu Rev Pharmacol Toxicol. 41:237-260. (Pubitemid 32385889)
25. Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD. 1998. Functional hypofrontality and working memory dysfunction in schizophrenia. Am J Psychiatry. 155:1285-1287. (Pubitemid 28402528)
26. Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, et al. 2005. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene × environment interaction. Biol Psychiatry. 57:1117-1127. (Pubitemid 40615773)
27. Cavada C, Goldman-Rakic PS. 1989. Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J Comp Neurol. 287:422-445. (Pubitemid 19239071)
28. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, et al. 2004. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet. 75:807-821. (Pubitemid 39390488)
29. Chen Q, He G, Chen Q, Wu S, Xu Y, Feng G, Li Y, Wang L, He L. 2005. A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population. Schizophr Res. 73:21.
30. Corbetta M, Kincade MJ, Lewis C, Snyder AZ, Sapir A. 2005. Neural basis and recovery of spatial attention deficits in spatial neglect. Nat Neurosci. 8:1603.
31. Coyle JT, Tsai G, Goff D. 2003. Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann N Y Acad Sci. 1003:318-327. (Pubitemid 38083065)
32. Curtis VA, Bullmore ET, Morris RG, Brammer MJ, Williams S C R, Simmons A, Sharma T, Murray RM, McGuire PK. 1999. Attenuated frontal activation in schizophrenia may be task dependent. Schizophr Res. 37:35-44. (Pubitemid 29167024)
33. Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. 1999. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry. 156:1328-1335. (Pubitemid 29416527)
34. Deco G, Rolls ET. 2005. Sequential memory: a putative neural and synaptic dynamical mechanism. J Cogn Neurosci. 17:294-307. (Pubitemid 40197524)
35. Deco G, Rolls ET, Horwitz B. 2004. "What" and "where" in visual working memory: a computational neurodynamical perspective for integrating fMRI and single-neuron data. J Cogn Neurosci. 16:683-701. (Pubitemid 38659553)
36. de Frias CM, Annerbrink K, Westberg L, Eriksson E, Adolfsson R, Nilsson LG. 2006. Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults. J Cogn Neurosci. 17:1018-1025.
37. D'Esposito M, Postle BR, Ballard D, Lease J. 1999. Maintenance versus manipulation of information held in working memory: an eventrelated fMRI study. Brain Cogn. 41:66-86. (Pubitemid 29487529)
38. Diamond A, Biriand L, Fossella J, Gehlbach L. 2004. Genetic and neurochemical modulation of prefrontal cognitive functions in children. Am J Psychiatry. 161:125-132. (Pubitemid 38419317)
39. Durstewitz D, Seamans JK. 2002. The computational role of dopamine D1 receptors in working memory. Neural Netw. 15:561-572. (Pubitemid 34951143)
40. Durstewitz D, Seamans JK, Sejnowski TJ. 2000. Neurocomputational models of working memory. Nat Neurosci. 3 Suppl: 1184-1191.
41. Egan MF, Goldberg TE, Gscheidle T, Weirich M, Rawlings R, Hyde TM, Bigelow L, Weinberger DR. 2001. Relativerisk forcognitiveimpairments in siblings of patients with schizophrenia. Biol Psychiatry. 50:98-107. (Pubitemid 32728209)
42. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. 2001. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA. 98:6917-6922. (Pubitemid 32538317)
43. Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, et al. 2004. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci USA. 101:12604-12609. (Pubitemid 39122071)
44. Fallin MD, Lasseter VK, Avramopoulos D, Nicodemus KK, Wolyniec PS, McGrath JA, Steel G, Nestadt G, Liang K-Y, Huganir RL, et al. 2005. Bipolar I disorder and schizophrenia: a 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios. Am J Hum Genet. 77:918-936. (Pubitemid 41698514)
45. Fan JB, Zhang CS, Gu NF, Li XW, Sun WW, Wang HY, Feng GY, St Clair D, Lin H. 2005. Catechol-O-methyltransferase gene val/met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol Psychiatry. 57:139-144.
46. Fletcher PC, McKenna PJ, Frith CD, Grasby PM, Friston KJ, Dolan RJ. 1998. Brain activations in schizophrenia during a graded memory task studied with functional neuroimaging. Arch Gen Psychiatry. 55:1001-1008. (Pubitemid 28506842)
47. Fuller R, Nopoulos P, Arndt S, O'Leary D, Ho BC, Andreasen NC. 2002. Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am J Psychiatry. 159:1183-1189. (Pubitemid 34743259)
48. Fuster JM. 1997. The prefrontal cortex-anatomy, physiology, and neuropsychology of the frontal lobe. Philadelphia, PA: Lippincott-Raven.
49. Fuster JM. 2000. Executive frontal functions. Exp Brain Res. 133:66.
50. Garey LJ, Ong WY, Patel TS, Kanna IM, Davis A, Mortimer AM, Barnes T R E, Hirsh SR. 1998. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry. 65:446-453. (Pubitemid 28438871)
51. Gevins A, Smith ME, McEvoy L, Yu D. 1997. High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb Cortex. 7:374-385. (Pubitemid 27231313)
52. Glahn DC, Ragland JD, Abramoff A, Barrett J, Laird AR, Bearden CE, Velligan DI. 2005. Beyond hypofrontality: a quantitative metaanalysis of functional neuroimaging studies of working memory in schizophrenia. Hum Brain Mapp. 25:60-69. (Pubitemid 40656193)
53. Glantz LA, Lewis DA. 2000. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry. 57:65-73. (Pubitemid 30035660)
54. Glatt SJ, Faraone SV, Tsuang MT. 2003. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatry. 160:469-476. (Pubitemid 41094254)
55. Gold JM, Carpenter C, Goldberg TE, Weinberger DR, Randolph C. 1997. Auditory working memory and Wisconsin card sorting test performance in schizophrenia. Arch Gen Psychiatry. 54:159.
56. Goldberg T, Egan M, Gscheidle T, Coppola R, Weickert T, Kolachana B, Goldman D, Weinberger D. 2003. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry. 60:889-896. (Pubitemid 37122307)
57. Goldberg TE, Patterson KJ, Taqqu Y, Wilder K. 1998. Capacity limitations in short-term memory in schizophrenia: tests of competing hypotheses. Psychol Med. 28:665-673. (Pubitemid 28241298)
58. Goldberg TE, Weinberger DR. 1988. Probing prefrontal function in schizophrenia with neuropsychological paradigms. Schizophr Bull. 14:179.
59. Goldberg TE, Weinberger DR. 1996. Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies. J Clin Psychiatry. 57:62-65. (Pubitemid 26327760)
60. Goldberg TE, Weinberger DR, Berman KF, Pliskin NH, Podd MH. 1987. Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry. 44:1008-1014. (Pubitemid 18009657)
61. Goldman-Rakic PS. 1987. Circuitry of primate prefrontal cortex and regulation of behavior by representational memory. In: Plum F, Mountcastle V, editors. Handbook of physiology: the nervous system V. Vol. 5. Bethesda, MD: American Physiological Society. p. 373-417.
62. Goldman-Rakic PS. 1988. Topography of cognition: parallel distributed networks in primate association cortex. Annu Rev Neurosci. 11:137-156.
63. Goldman-Rakic PS. 1990. Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. Prog Brain Res. 85:325-336.
64. Goldman-Rakic PS. 1994. Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci. 6:348-357. (Pubitemid 24344855)
65. Goldman-Rakic PS. 1995. Cellular basis of working memory. Neuron. 14:477.
66. Goldman-Rakic PS. 1996. Regional and cellular fractionation of working memory. Proc Natl Acad Sci USA. 93:13473-13480. (Pubitemid 26424144)
67. Goldman-Rakic PS. 1999. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry. 46:650-661. (Pubitemid 29401861)
68. Green MF. 1996. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 153:321-330. (Pubitemid 26074706)
69. Harrison PJ. 1999. The neuropathology of schizophrenia-a critical review of the data and their interpretation. Brain. 122:593-624. (Pubitemid 29158770)
70. Harrison PJ, Weinberger DR. 2005. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry. 10:40-68. (Pubitemid 40139588)
71. Honey R A E, Honey GD, O'Loughlin C, Sharar SR, Kumaran D, Bullmore ET, Menon DK, Donovan T, Lupson VC, Bisbrown-Chippendale R, et al. 2004. Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an fMRI study. Neuropsychopharmacology. 29:1203-1214. (Pubitemid 38670056)
72. Horwitz B, Poeppel D. 2002. How can EEG/MEG and fMRI/PET data be combined? Hum Brain Mapp. 17:1-3. (Pubitemid 34966790)
73. Insel TR, Scolnick EM. 2006. Cure therapeutics and strategic prevention: raising the bar for mental health research. Mol Psychiatry. 11:11-17. (Pubitemid 43251083)
74. Jansma JM, Ramsey NF, van der Wee N J A, Kahn RS. 2004. Working memory capacity in schizophrenia: a parametric fMRI study. Schizophr Res. 68:159-171. (Pubitemid 38526140)
75. Johansen-Berg H, Rushworth M F S, Bogdanovic MD, Kischka U, Wimalaratna S, Matthews PM. 2002. The role of ipsilateral premotor cortex in hand movement after stroke. Proc Natl Acad Sci USA. 99:14518-14523. (Pubitemid 35257703)
76. Jones P, Rodgers B, Murray R, Marmot M. 1994. Child developmental risk-factors for adult schizophrenia in the British 1946 birth cohort. Lancet. 344:1398-1402. (Pubitemid 24365314)
77. Jonides J, Schumacher EH, Smith EE, Koeppe RA, Awh E, Reuter-Lorenz PA, Marshuetz C, Willis CR. 1998. The role of parietal cortex in verbal working memory. J Neurosci. 18:5026-5034. (Pubitemid 28285411)
78. Just MA, Carpenter PA. 1996. A capacity theory of comprehension: individual differences in working memory. Psychol Rev. 103:122-149.
79. Keefe R S E, Lees Roitman SE, Harvey PD, Blum CS, DuPre RL, Prieto DM, Davidson M, Davis KL. 1995. A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia. Schizophr Res. 17:25.
80. Kim D-S, Kim M. 2005. Combining functional and diffusion tensor MRI. Ann N Y Acad Sci. 1064:1-15. (Pubitemid 43030945)
81. Kim JH, Glahn DC, Nuechterlein KH, Cannon TD. 2004. Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory. Schizophr Res. 68:173-187. (Pubitemid 38526141)
82. Kim JJ, Kwon JS, Park HJ, Youn T, Kang DH, Kim MS, Lee DS, Lee MC. 2003. Functional disconnection between the prefrontal and parietal cortices during working memory processing in schizophrenia: A O-15 H2O PET study. Am J Psychiatry. 160:919-923. (Pubitemid 41079577)
83. Koechlin E, Ody C, Kouneiher FT. 2003. The architecture of cognitive control in the human prefrontal cortex. Science. 302:1181-1185. (Pubitemid 37421016)
84. Krystal JH, Perry EB Jr, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, MacDougall L, Abi-Saab W, D'Souza DC. 2005. Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry. 62:985-994.
85. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. 1996. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 6:243.
86. Laruelle M, Kegeles LS, Abi-Dargham A. 2003. Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci. 1003:138-158. (Pubitemid 38083052)
87. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I, Williams NM, Schwab SG, Pulver AE, Faraone SV, et al. 2003. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet. 73:34-48. (Pubitemid 36793778)
88. Lewis DA, Cruz D, Eggan S, Erickson S. 2004. Postnatal development of prefrontal inhibitory circuits and the pathophysiology of cognitive dysfunction in schizophrenia. Ann N Y Acad Sci USA. 1021:64-76. (Pubitemid 38879612)
89. Lewis DA, Melchitzky DS, Seasack SR, Whitehead RE, Sungyoung A U H, Sampson A. 2001. Dopamine transporter immunoreactivity in monkey cerebral cortex. J Comp Neurol. 432:119-136.
90. Lisman JE, Fellous JM, Wang XJ. 1998. A role for NMDA-receptor channels in working memory. Nat Neurosci. 1:273-275. (Pubitemid 128652671)
91. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J. 1995. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry (Mosc). 34:4202.
92. MacDonald AW 3rd, Carter CS, Kerns JG, Ursu S, Barch DM, Holmes AJ, Stenger VA, Cohen JD. 2005. Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. Am J Psychiatry. 162:475-484. (Pubitemid 40343914)
93. Malhotra AK, Kestler LJ, Mazzanti C, Bates JA, Goldberg T, Goldman D. 2002. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry. 159:652-654. (Pubitemid 34274949)
94. Manoach DS. 2003. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res. 60:285-298. (Pubitemid 36184716)
95. Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E, Saper CB, Rauch SL. 2000. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry. 48:99-109. (Pubitemid 30618799)
96. Manoach DS, Press DZ, Thangara JV, Searl MM, Goff DC, Halpern E, Saper CB, Warach S. 1999. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task as measured by fMRI. Biol Psychiatry. 45:1128-1137. (Pubitemid 29236553)
97. Marti SB, Cichon S, Propping P, Nothen M. 2002. Metabotropic glutamate receptor 3 (GRM3) gene variation is not associated with schizophrenia or bipolar affective disorder in the German population. Am J Med Genet. 114:46-50.
98. Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR. 2003. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA. 100:6186-6191. (Pubitemid 36576952)
99. McGlashan TH, Hoffman RE. 2000. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch Gen Psychiatry. 57:637-648. (Pubitemid 30445855)
100. Menon V, Anagnoson RT, Mathalon DH, Glover GH, Pfefferbaum A. 2001. Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms. Neuro Image. 13:433.
101. Meyer-Lindenberg A, Kohn PD, Kolachana B, Kippenhan S, McInerney-Leo A, Nussbaum R, Weinberger DR, Berman KF. 2005. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nat Neurosci. 8:594-596. (Pubitemid 40594200)
102. Meyer-Lindenberg A, Poline J-B, Kohn PD, Holt JL, Egan MF, Weinberger DR, Berman KF. 2001. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiatry. 158:1809-1817. (Pubitemid 33054773)
103. Meyer-Lindenberg AS, Nichols T, Callicott JH, Ding J, Kolachana BS, Buckholtz J, Mattay VS, Egan MF, Weinberger DR. 2006. Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry. 11:867-877. (Pubitemid 44299108)
104. Meyer-Lindenberg AS, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberger DR, Berman KF. 2005. Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch Gen Psychiatry. 62:379-386. (Pubitemid 40471687)
105. Meyer-Lindenberg AS, Weinberger DR. 2006. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci. 7:818-827. (Pubitemid 44435264)
106. Moghaddam B. 2003. Bringing order to the glutamate chaos in schizophrenia. Neuron. 40:881-884. (Pubitemid 37522046)
107. Moghaddam B, Adams BW. 1998. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science. 281:1349-1352. (Pubitemid 28406826)
108. Murphy KC. 2002. Schizophrenia and velo-cardio-facial syndrome. Lancet. 359:426-430. (Pubitemid 34158957)
109. Nolan KA, Bilder RM, Lachman HM, Volavka J. 2004. Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Val and Met alleles on cognitive stability and flexibility. Am J Psychiatry. 161:359-361. (Pubitemid 38419288)
110. Norton N, Williams H, Dwyer S, Ivanov D, Preece A, Gerrish A, Williams N, Yerassimou P, Zammit S, O'Donovan M, et al. 2005. No evidence for association between polymorphisms in GRM3 and schizophrenia. BMC Psychiatry. 5:23.
111. Park S, Holzman PS. 1992. Schizophrenics show spatial working memory deficits. Arch Gen Psychiatry. 49:975.
112. Paulesu E, Frith CD, Frackowiak RS. 1993. The neural correlates of the verbal component of working memory. Nature. 362:342-345. (Pubitemid 23101305)
113. Perlstein W, Carter C, Noll D, Cohen J. 2001. Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. Am J Psychiatry. 158:1105-1113. (Pubitemid 32623115)
114. Perlstein WM, Dixit NK, Carter CS, Noll DC, Cohen JD. 2003. Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia. Biol Psychiatry. 53:25-38. (Pubitemid 36050933)
115. Petersen SE, van Mier H, Fiez JA, Raichle ME. 1998. The effects of practice on the functional anatomy of task performance. Proc Natl Acad Sci USA. 95:853-860. (Pubitemid 28124878)
116. Petrides M, Pandya DN. 1984. Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J Comp Neurol. 228:105-116. (Pubitemid 14061782)
117. Ramsey NF, Jansma JM, Jager G, Van Raalten T, Kahn RS. 2004. Neurophysiological factors in human information processing capacity. Brain. 127:517-525. (Pubitemid 38295469)
118. Ramsey NF, Koning HA, Welles P, Cahn W, Van der Linden JA, Kahn RS. 2002. Excessive recruitment of neural systems subserving logical reasoning in schizophrenia. Brain. 125:1793-1807.
119. Rypma B, D'Esposito M. 1999. The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences. Proc Natl Acad Sci USA. 96:6558-6563. (Pubitemid 29256705)
120. Sartorius LJ, Nagappan G, Lipska BK, Lu B, Sei Y, Ren-Patterson R, Li Z, Weinberger DR, Harrison PJ. 2006. Alternative splicing of human metabotropic glutamate receptor 3. J Neurochem. 96:1139-1148.
121. Sawaguchi T, Goldman-Rakic PS. 1991. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science. 251:947-950. (Pubitemid 21926192)
122. Sawaguchi T, Goldman-Rakic PS. 1994. The role of D1-dopamine receptor in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task. J Neurophysiol. 71:515-528. (Pubitemid 24068583)
123. Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P. 2003. Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling. Neuro Image. 19:751-763. (Pubitemid 36918218)
124. Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Stoeter P. 2003. Altered effective connectivity in drug free schizophrenic patients. Neuro Report. 14:2233-2237.
125. Seamans JK, Durstewitz D, Christie BR, Stevens CF, Sejnowski TJ. 2001. Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons. Proc Natl Acad Sci USA. 98:301-306. (Pubitemid 32095904)
126. Seamans JK, Gorelova N, Durstewitz D, Yang CR. 2001. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J Neurosci. 21:3628.
127. Seamans JK, Yang CR. 2004. The principal features and mechanisms of dopamine modulationinthe prefrontalcortex. Prog Neurobiol. 74:1-57. (Pubitemid 39286053)
128. Seasack SR, Hawrylak VA, Matus C, Guido MA, Levey AI. 1998. Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J Neurosci. 18:2697-2708. (Pubitemid 28141815)
129. Selemon LD, Goldman-Rakic PS. 1985. Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci. 5:776-794. (Pubitemid 15100467)
130. Selemon LD, Goldman-Rakic PS. 1999. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry. 45:17-25. (Pubitemid 29049200)
131. Selemon LD, Mrzljak J, Kleinman JE, Herman MM, Goldman-Rakic PS. 2003. Regional specificity in the neuropathologic substrates of schizophrenia-a morphometric analysis of Broca's area 44 and area 9. Arch Gen Psychiatry. 60:69-77. (Pubitemid 36070867)
132. Serrien DJ, Ivry RB, Swinnen SP. 2006. Dynamics of hemispheric specialization and integration in the context of motor control. Nat Rev Neurosci. 7:160.
133. Sesack SR, Carr DB, Omelchenko N, Pinto A. 2003. Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynaptic actions. Ann N Y Acad Sci. 1003:36-52. (Pubitemid 38083044)
134. Shadmehr R, Holcomb HH. 1997. Neural correlates of motor memory consolidation. Science. 277:821-825. (Pubitemid 27366734)
135. Shallice T. 1988. From neuropsychology to mental structure. Cambridge (MA): Cambridge University Press.
136. Silver H, Feldman P, Bilker WB, Gur RC. 2003. Working memory deficit as a core neuropsychological dysfunction in schizophrenia. Am J Psychiatry. 160:1809-1816. (Pubitemid 41103315)
137. Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley RW. 2004. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc Natl Acad Sci USA. 101:17288-17293. (Pubitemid 39627812)
138. Stevens AA, Goldman-Rakic PS, Gore JC, Fulbright RK, Wexler BE. 1998. Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging. Arch Gen Psychiatry. 55:1097-1103. (Pubitemid 28558282)
139. Tamminga CA, Lahti AC, Medoff DR, Gao XM, Holcomb HH. 2003. Evaluating glutamatergic transmission in schizophrenia. Ann N Y Acad Sci. 1003:113-118. (Pubitemid 38083049)
140. Tan HY, Choo WC, Fones C S L, Chee M W L. 2005. fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. Am J Psychiatry. 162:1849-1858. (Pubitemid 41428614)
141. Tan HY, Sust S, Buckholtz JW, Mattay VS, Meyer-Lindenberg AS, Egan MF, Weinberger DR, Callicott JH. 2006. Dysfunctional prefrontal regional specialization and compensation in schizophrenia. Am J Psychiatry. 163:1969-1977. (Pubitemid 44807789)
142. Tan HY, Chen Q, Sust S, Buckholtz JW, Meyers J, Egan M, Mattay VS, Meyer-Lindenberg A, Weinberger DR, Callicott JH. 2007. Evidence of biologic epistasis between COMT and GRM3 on human prefrontal function during working memory. Proc Natl Acad Sci USA. (In press).
143. The International Hap Map Consortium. 2005. A haplotype map of the human genome. Nature. 437:1299-1320.
144. Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. 2001. From the cover: mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci USA. 98:11650-11655. (Pubitemid 32928783)
145. Toga AW, Thompson PM, Sowell ER. 2006. Mapping brain maturation. Trends Neurosci. 29:148-159.
146. Vijayraghavan S, Wang M, Birnbaum SG, Williams GV, Arnsten A F T. 2007. Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci. 10:376-384.
147. Wang J, O'Donnell P. 2001. D1 dopamine receptors potentiate NMDA-mediated excitability increase in layer v prefrontal cortical pyramidal neurons. Cereb Cortex. 11:452-462. (Pubitemid 32428071)
148. Wang X-J. 1999. Synaptic basis of cortical persistent activity: the importance of NMDA receptors to working memory. J Neurosci. 19:9587-9603. (Pubitemid 30228110)
149. Wang XJ. 2001. Synaptic reverberation underlying mnemonic persistent activity. Trends Neurosci. 24:455-463.
150. Weickert TW, Goldberg TE, Gold JM, Bigelow LB, Egan MF, Weinberger DR. 2000. Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect. Arch Gen Psychiatry. 57:907-913.
151. Weickert TW, Goldberg TE, Mishara A, Apud JA, Kolachana BS, Egan MF, Weinberger DR. 2004. Catechol-O-methyltransferase val108/158met genotype predicts working memory response to antipsychotic medications. Biol Psychiatry. 56:677.
152. Weinberger DR. 1987. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 44:660-669. (Pubitemid 17099795)
153. Weinberger DR, Berman K, Zec R. 1986. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: I. Regional cerebral blood flow evidence. Arch Gen Psychiatry. 43:114-124. (Pubitemid 16163530)
154. Weinberger DR, Berman KF. 1996. Prefrontal function in schizophrenia: confounds and controversies. Philos Trans R Soc Lond B Biol Sci. 351:1495-1503. (Pubitemid 27005376)
155. Weinberger DR, Berman KF, Illowsky BP. 1988. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism. Arch Gen Psychiatry. 45:609-615.
156. Weinberger DR, Egan MF, Bertolino A, Callicott JH, Mattay VS, Lipska BK, Berman KF, Goldberg TE. 2001. Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry. 50:825-844. (Pubitemid 34020697)
157. Whalley HC, Simonotto E, Flett S, Marshall I, Ebmeier KP, Owens D G C, Goddard NH, Johnstone EC, Lawrie SM. 2004. fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. Brain. 127:478.
158. Whalley HC, Simonotto E, Moorhead W, McIntosh A, Marshall I, Ebmeier KP, Owens D G C, Goddard NH, Johnstone EC, Lawrie SM. 2006. Functional imaging as a predictor of schizophrenia. Biol Psychiatry. 60:454-462. (Pubitemid 44292155)
159. Williams GV, Goldman-Rakic PS. 1995. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature. 376:572-575.
160. Winterer G, Egan MF, Kolachana BS, Goldberg TE, Coppola R, Weinberger DR. 2006. Prefrontal electrophysiologic "noise" and catechol-O- methyltransferase genotype in schizophrenia. Biol Psychiatry. 60:578-584. (Pubitemid 44402372)
161. Winterer G, Musso F, Beckmann C, Mattay V, Egan MF, Jones DW, Callicott JH, Coppola R, Weinberger DR. 2006. Instability of prefrontal signal processing in schizophrenia. Am J Psychiatry. 163:1960-1968. (Pubitemid 44807788)
162. Winterer G, Weinberger DR. 2004. Genes, dopamine and cortical signalto-noise ratio in schizophrenia. Trends Neurosci. 27:683-690. (Pubitemid 39335839)