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Monoamine-Based Treatments in Schizophrenia: Time to Change the Paradigm?

  • Rodrigo D. Paz
  • Kuei-Yuan Tseng

Functional deficit in the prefrontal cortex (PFC), also known as hypofrontality, is one of the major manifestations in schizophrenia. This is characterized by a failure of the PFC to support behavior. Although the neuronal mechanisms underlying hyporontality are still under debate, most of the neuroimaging findings have been consistent with a hypofunctional PFC state in response to working memory tasks. These cognitive impairments are typically evidenced by lack of PFC activation (for review see Manoach, 2003). However, there are also studies showing either no changes or increased activation of the dorsolateral PFC (Manoach et al., 1999, 2000; Callicott et al., 2000, 2003a, b; Honey et al., 2002). Perhaps these apparently contradictory findings could simply reflect the different strategy used to examine PFC activation and the nonlinear relationship between PFC activation and task demand (Braver et al., 1997; Goldberg et al., 1998; Callicott et al., 1999; Manoach, 2003). PFC response increases parametrically with working memory load until the demand exceeds the functional capacity, during which activation decrease. Despite the fact that patients suffering schizophrenia usually exhibit a relative lower task performance than controls, a similar nonlinear relationship between PFC activation and task demand may also exist in schizophrenia, but shifted toward the left of the curve. A relative decrease or increase of PFC activation could be obtained in schizophrenia subjects depending on the loads required to perform the task and the actual cortical functional level.

Since the early 1950s to our days, pharmacologically oriented treatments in schizophrenia have been monopolized by monoamine modulating drugs. Beginning with the first generation of relatively pure dopamine (DA) antagonists followed by a second generation of antipsychotic drugs with dual DA and serotonin (5HT) antagonist effects, and more recently by partial DA agonists and acetylcholine (Ach) receptor modulating drugs, modern pharmacological interventions in schizophrenia have been fueled with the idea of changing the curse of this devastating disorder by modifying brain monoamine function. However, despite the effectiveness of treating psychotic symptoms, these monoamine-based drugs have very limited effect in restoring the cognitive and emotional disabilities associated to schizophrenia.

In this chapter we will discuss and provide insights on how and why drugs that target the central monoamine system are not necessary effective to prevent cognitive and emotional impairments in schizophrenia. We will summarize evidence indicating that this failure in treating cognitive deficits could be caused by at least two factors. First, most of the cognitive and emotional deteriorations in schizophrenia appear during early adolescence, years before the emergence of psychosis. Secondly, DA antagonists may interfere with several neuronal signaling pathways critically involved in maintaining normal cognitive functions. We hypothesize that a new generation of glutamate modulating drugs could be used to prevent cognitive deteriorations related to schizophrenia in high risk adolescents.

Keywords

Prefrontal Cortex NMDA Receptor Antipsychotic Drug NMDA Antagonist Biol Psychiatry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, B. and Moghaddam, B. (1998) Corticolimbic dopamine neurotransmission is tempo-rally dissociated from the cognitive and locomotor effects of phencyclidine. J Neurosci. 18, 5545-5554.PubMedGoogle Scholar
  2. Adler, C.M., Malhotra, A.K., Elman, I., Goldberg, T., Egan, M., Pickar, D. and Breier, A. (1999) Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia. Am J Psychiatry. 156, 1646-1649.PubMedGoogle Scholar
  3. Ang, Y.G. and Tan, H.Y. (2004) Academic deterioration prior to first episode schizophrenia in young Singaporean males. Psychiatry Res. 121, 303-307.PubMedGoogle Scholar
  4. Arnsten, A.F. (2004) Adrenergic targets for the treatment of cognitive deficits in schizophre-nia. Psychopharmacology (Berl). 174, 25-31.Google Scholar
  5. Arnsten, A.F. and Goldman-Rakic, P.S. (1998) Noise stress impairs prefrontal cortical cogni-tive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch Gen Psy-chiatry. 55, 362-368.Google Scholar
  6. Arnsten, A.F. and Li, B.M. (2005) Neurobiology of executive functions: catecholamine influ-ences on prefrontal cortical functions. Biol Psychiatry. 57, 1377-1384.PubMedGoogle Scholar
  7. Azorin, J.M., Spiegel, R., Remington, G., Vanelle, J.M., Pere, J.J., Giguere, M. and Bourdeix, I. (2001) A double-blind comparative study of clozapine and risperidone in the manage-ment of severe chronic schizophrenia. Am J Psychiatry. 158, 1305-1313.PubMedGoogle Scholar
  8. Bartha, R., Williamson, P.C., Drost, D.J., Malla, A., Carr, T.J., Cortese, L., Canaran, G., Rylett, R.J. and Neufeld, R.W. (1997) Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 54, 959-965.PubMedGoogle Scholar
  9. Benes, F.M., Walsh, J., Bhattacharyya, S., Sheth, A. and Berretta, S. (2003) DNA fragmenta-tion decreased in schizophrenia but not bipolar disorder. Arch Gen Psychiatry. 60, 359-364.PubMedGoogle Scholar
  10. Benes, F.M., Matzilevich, D., Burke, R.E. and Walsh, J. (2006) The expression of proapop-tosis genes is increased in bipolar disorder, but not in schizophrenia. Mol Psychiatry. 11, 241-251.PubMedGoogle Scholar
  11. Bergson, C., Levenson, R., Goldman-Rakic, P.S. and Lidow, M.S. (2003) Dopamine receptor-interacting proteins: the Ca(2+) connection in dopamine signaling. Trends Pharmacol Sci. 24, 486-492.PubMedGoogle Scholar
  12. Braver, T.S., Cohen, J.D., Nystrom, L.E., Jonides, J., Smith, E.E. and Noll, D.C. (1997) A parametric study of prefrontal cortex involvement in human working memory. Neuroi-mage. 5, 49-62.Google Scholar
  13. Breier, A., Malhotra, A.K., Pinals, D.A., Weisenfeld, N.I. and Pickar, D. (1997) Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry. 154, 805-811.PubMedGoogle Scholar
  14. Breier, A.F., Malhotra, A.K., Su, T.P., Pinals, D.A., Elman, I., Adler, C.M., Lafargue, R.T., Clifton, A. and Pickar, D. (1999) Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. Am J Psy-chiatry. 156, 294-298.Google Scholar
  15. Bustillo, J.R., Buchanan, R.W., Irish, D. and Breier, A. (1996) Differential effect of clozapine on weight: a controlled study. Am J Psychiatry. 153, 817-819.PubMedGoogle Scholar
  16. Cai, J.X. and Arnsten, A.F. (1997) Dose-dependent effects of the dopamine D1 receptor ago-nists A77636 or SKF81297 on spatial working memory in aged monkeys. J Pharmacol Exp Ther. 283, 183-189.PubMedGoogle Scholar
  17. Callicott, J.H., Mattay, V.S., Bertolino, A., Finn, K., Coppola, R., Frank, J.A., Goldberg, T.E. and Weinberger, D.R. (1999) Physiological characteristics of capacity constraints in work-ing memory as revealed by functional MRI. Cereb Cortex. 9, 20-26.PubMedGoogle Scholar
  18. Callicott, J.H., Bertolino, A., Mattay, V.S., Langheim, F.J., Duyn, J., Coppola, R., Goldberg, T.E. and Weinberger, D.R. (2000) Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex. 10, 1078-1092.PubMedGoogle Scholar
  19. Callicott, J.H., Egan, M.F., Mattay, V.S., Bertolino, A., Bone, A.D., Verchinksi, B. and Weinberger, D.R. (2003a) Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry. 160, 709-719.PubMedGoogle Scholar
  20. Callicott, J.H., Mattay, V.S., Verchinski, B.A., Marenco, S., Egan, M.F. and Weinberger, D.R. (2003b) Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am J Psychiatry. 160, 2209-2215.PubMedGoogle Scholar
  21. Carpenter, W.T. (2004) Carpenter WT. Is glutamatergic therapy efficacious in schizophrenia? ACNP, San Juan, Puerto Rico.Google Scholar
  22. Carpenter, W.T. and Gold, J.M. (2002) Another view of therapy for cognition in schizophre-nia. Biol Psychiatry. 51, 969-971.PubMedGoogle Scholar
  23. Castner, S.A., Williams, G.V. and Goldman-Rakic, P.S. (2000) Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Sci-ence. 287, 2020-2022.Google Scholar
  24. Chakos, M., Lieberman, J., Hoffman, E., Bradford, D. and Sheitman, B. (2001) Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. Am J Psychiatry. 158, 518-526.PubMedGoogle Scholar
  25. Chou, Y.H., Halldin, C. and Farde, L. (2006) Clozapine binds preferentially to cortical D1-like dopamine receptors in the primate brain: a PET study. Psychopharmacology (Berl). 185, 29-35.Google Scholar
  26. Cohen, S., Chiles, J. and MacNaughton, A. (1990) Weight gain associated with clozapine. Am J Psychiatry. 147, 503-504.PubMedGoogle Scholar
  27. Conley, R.R., Tamminga, C.A., Kelly, D.L. and Richardson, C.M. (1999) Treatment-resistant schizophrenic patients respond to clozapine after olanzapine non-response. Biol Psychia-try. 46, 73-77.Google Scholar
  28. Cosway, R., Byrne, M., Clafferty, R., Hodges, A., Grant, E., Abukmeil, S.S., Lawrie, S.M., Miller, P. and Johnstone, E.C. (2000) Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Psychol Med. 30, 1111-1121.PubMedGoogle Scholar
  29. Damadzic, R., Bigelow, L.B., Krimer, L.S., Goldenson, D.A., Saunders, R.C., Kleinman, J.E. and Herman, M.M. (2001) A quantitative immunohistochemical study of astrocytes in the entorhinal cortex in schizophrenia, bipolar disorder and major depression: absence of sig-nificant astrocytosis. Brain Res Bull. 55, 611-618.PubMedGoogle Scholar
  30. Davis, J.M., Chen, N. and Glick, I.D. (2003) A meta-analysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry. 60, 553-564.PubMedGoogle Scholar
  31. Dorph-Petersen, K.A., Pierri, J.N., Perel, J.M., Sun, Z., Sampson, A.R. and Lewis, D.A. (2005) The influence of chronic exposure to antipsychotic medications on brain size be-fore and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology. 30, 1649-1661.PubMedGoogle Scholar
  32. Eastwood, S.L., Burnet, P.W. and Harrison, P.J. (2005) Decreased hippocampal expression of the susceptibility gene PPP3CC and other calcineurin subunits in schizophrenia. Biol Psy-chiatry. 57, 702-710.Google Scholar
  33. Freedman, R. (2005) The choice of antipsychotic drugs for schizophrenia. N Engl J Med. 353, 1286-1288.PubMedGoogle Scholar
  34. Fuller, R., Nopoulos, P., Arndt, S., O’Leary, D., Ho, B.C. and Andreasen, N.C. (2002) Longi-tudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am J Psychiatry. 159, 1183-1189.PubMedGoogle Scholar
  35. Gardner, D.M., Baldessarini, R.J. and Waraich, P. (2005) Modern antipsychotic drugs: a critical overview. CMAJ. 172, 1703-1711.PubMedGoogle Scholar
  36. Gerber, D.J., Hall, D., Miyakawa, T., Demars, S., Gogos, J.A., Karayiorgou, M. and Tonegawa, S. (2003) Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit. Proc Natl Acad Sci USA. 100, 8993-8998.PubMedGoogle Scholar
  37. Giedd, J.N., Blumenthal, J., Jeffries, N.O., Castellanos, F.X., Liu, H., Zijdenbos, A., Paus, T., Evans, A.C. and Rapoport, J.L. (1999) Brain development during childhood and adoles-cence: a longitudinal MRI study. Nat Neurosci. 2, 861-863.PubMedGoogle Scholar
  38. Goff, D.C. and Coyle, J.T. (2001) The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry. 158, 1367-1377.PubMedGoogle Scholar
  39. Goff, D.C., Tsai, G., Levitt, J., Amico, E., Manoach, D., Schoenfeld, D.A., Hayden, D.L., McCarley, R. and Coyle, J.T. (1999) A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry. 56, 21-27.PubMedGoogle Scholar
  40. Gogtay, N., Giedd, J.N., Lusk, L., Hayashi, K.M., Greenstein, D., Vaituzis, A.C., Nugent, T.F., 3rd, Herman, D.H., Clasen, L.S., Toga, A.W., Rapoport, J.L. and Thompson, P.M. (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA. 101, 8174-8179.PubMedGoogle Scholar
  41. Goldberg, T.E., Berman, K.F., Fleming, K., Ostrem, J., Van Horn, J.D., Esposito, G., Mattay, V.S., Gold, J.M. and Weinberger, D.R. (1998) Uncoupling cognitive workload and pre-frontal cortical physiology: a PET rCBF study. Neuroimage. 7, 296-303.PubMedGoogle Scholar
  42. Grunze, H.C., Rainnie, D.G., Hasselmo, M.E., Barkai, E., Hearn, E.F., McCarley, R.W. and Greene, R.W. (1996) NMDA-dependent modulation of CA1 local circuit inhibition. J Neurosci. 16, 2034-2043.PubMedGoogle Scholar
  43. Hardingham, G.E., Fukunaga, Y. and Bading, H. (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci. 5, 405-414.PubMedGoogle Scholar
  44. Harrison, P.J. (1999) The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain. 122 ( Pt 4), 593-624.PubMedGoogle Scholar
  45. Hegarty, J.D., Baldessarini, R.J., Tohen, M., Waternaux, C. and Oepen, G. (1994) One hun-dred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry. 151, 1409-1416.PubMedGoogle Scholar
  46. Henderson, D.C., Cagliero, E., Gray, C., Nasrallah, R.A., Hayden, D.L., Schoenfeld, D.A. and Goff, D.C. (2000) Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study. Am J Psychiatry. 157, 975-981.PubMedGoogle Scholar
  47. Ho, B.C., Alicata, D., Ward, J., Moser, D.J., O’Leary, D.S., Arndt, S. and Andreasen, N.C. (2003) Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. Am J Psychiatry. 160, 142-148.PubMedGoogle Scholar
  48. Holcomb, H.H., Lahti, A.C., Medoff, D.R., Weiler, M. and Tamminga, C.A. (2001) Sequential regional cerebral blood flow brain scans using PET with H2(15)O demonstrate ketamine actions in CNS dynamically. Neuropsychopharmacology. 25, 165-172.PubMedGoogle Scholar
  49. Holcomb, H.H., Lahti, A.C., Medoff, D.R., Cullen, T. and Tamminga, C.A. (2005) Effects of noncompetitive NMDA receptor blockade on anterior cingulate cerebral blood flow in volunteers with schizophrenia. Neuropsychopharmacology. 30, 2275-2282.PubMedGoogle Scholar
  50. Honey, G.D., Bullmore, E.T. and Sharma, T. (2002) De-coupling of cognitive performance and cerebral functional response during working memory in schizophrenia. Schizophr Res. 53, 45-56.PubMedGoogle Scholar
  51. Huttenlocher, P.R. (1979) Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res. 163, 195-205.PubMedGoogle Scholar
  52. Jackson, M.E., Homayoun, H. and Moghaddam, B. (2004) NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex. Proc Natl Acad Sci USA. 101, 8467-8472.PubMedGoogle Scholar
  53. Javitt, D.C. and Zukin, S.R. (1991) Recent advances in the phencyclidine model of schizo-phrenia. Am J Psychiatry. 148, 1301-1308.PubMedGoogle Scholar
  54. Jay, T.M. (2003) Dopamine: a potential substrate for synaptic plasticity and memory mecha-nisms. Prog Neurobiol. 69, 375-390.PubMedGoogle Scholar
  55. Jernigan, T.L., Trauner, D.A., Hesselink, J.R. and Tallal, P.A. (1991) Maturation of human cerebrum observed in vivo during adolescence. Brain. 114 (Pt 5), 2037-2049.PubMedGoogle Scholar
  56. Jodo, E., Suzuki, Y., Katayama, T., Hoshino, K.Y., Takeuchi, S., Niwa, S. and Kayama, Y. (2005) Activation of medial prefrontal cortex by phencyclidine is mediated via a hippo-campo-prefrontal pathway. Cereb Cortex. 15, 663-669.PubMedGoogle Scholar
  57. Kapur, S., Langlois, X., Vinken, P., Megens, A.A., De Coster, R. and Andrews, J.S. (2002) The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats. J Pharmacol Exp Ther. 302, 1129-1134.PubMedGoogle Scholar
  58. Kane J, Honigfeld G, Singer J, Meltzer H. (1988) Clozapine for the treatment-resistant schizophrenic. Adouble-blind comparison with chlorpromazine. Arch Gen Psychiatry 45 (9): 789-96.PubMedGoogle Scholar
  59. Keefe, R.S., Seidman, L.J., Christensen, B.K., Hamer, R.M., Sharma, T., Sitskoorn, M.M., Rock, S.L., Woolson, S., Tohen, M., Tollefson, G.D., Sanger, T.M. and Lieberman, J.A. (2006a) Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biol Psychiatry. 59, 97-105.PubMedGoogle Scholar
  60. Keefe, R.S., Young, C.A., Rock, S.L., Purdon, S.E., Gold, J.M. and Breier, A. (2006b) One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia. Schizophr Res. 81, 1-15.PubMedGoogle Scholar
  61. Kellendonk, C., Simpson, E.H., Polan, H.J., Malleret, G., Vronskaya, S., Winiger, V., Moore, H. and Kandel, E.R. (2006) Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron. 49, 603-615.PubMedGoogle Scholar
  62. Koh, P.O., Bergson, C., Undie, A.S., Goldman-Rakic, P.S. and Lidow, M.S. (2003) Up-regulation of the D1 dopamine receptor-interacting protein, calcyon, in patients with schizophrenia. Arch Gen Psychiatry. 60, 311-319.PubMedGoogle Scholar
  63. Krystal, J.H., Karper, L.P., Seibyl, J.P., Freeman, G.K., Delaney, R., Bremner, J.D., Heninger, G.R., Bowers, M.B., Jr. and Charney, D.S. (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 51, 199-214.PubMedGoogle Scholar
  64. Krystal, J.H., D'Souza, D.C., Mathalon, D., Perry, E., Belger, A. and Hoffman, R. (2003) NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology (Berl). 169, 215-233.Google Scholar
  65. Lamberti, J.S., Olson, D., Crilly, J.F., Olivares, T., Williams, G.C., Tu, X., Tang, W., Wiener, K., Dvorin, S. and Dietz, M.B. (2006) Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry. 163, 1273-1276.PubMedGoogle Scholar
  66. Lencz, T., Smith, C.W., McLaughlin, D., Auther, A., Nakayama, E., Hovey, L. and Cornblatt, B.A. (2006) Generalized and specific neurocognitive deficits in prodromal schizophrenia. Biol Psychiatry. 59, 863-871.PubMedGoogle Scholar
  67. Leslie, C.A., Robertson, M.W., Cutler, A.J. and Bennett, Jr., J.P., (1991) Postnatal develop-ment of D1 dopamine receptors in the medial prefrontal cortex, striatum and nucleus accumbens of normal and neonatal 6-hydroxydopamine treated rats: a quantitative autora-diographic analysis. Brain Res Dev Brain Res. 62, 109-114.PubMedGoogle Scholar
  68. Lewis, D.A. and Levitt, P. (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci. 25, 409-432.PubMedGoogle Scholar
  69. Lewis, S.W. and Murray, R.M. (1987) Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. J Psychiatr Res. 21, 413-421.PubMedGoogle Scholar
  70. Lewis, D.A., Hashimoto, T. and Volk, D.W. (2005) Cortical inhibitory neurons and schizo-phrenia. Nat Rev Neurosci. 6, 312-324.PubMedGoogle Scholar
  71. Lieberman, J.A. (1999) Is schizophrenia a neurodegenerative disorder? A clinical and neuro-biological perspective. Biol Psychiatry. 46, 729-739.PubMedGoogle Scholar
  72. Lieberman, J., Chakos, M., Wu, H., Alvir, J., Hoffman, E., Robinson, D. and Bilder, R. (2001a) Longitudinal study of brain morphology in first episode schizophrenia. Biol Psy-chiatry. 49, 487-499.Google Scholar
  73. Lieberman, J.A., Perkins, D., Belger, A., Chakos, M., Jarskog, F., Boteva, K. and Gilmore, J. (2001b) The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry. 50, 884-897.PubMedGoogle Scholar
  74. Lieberman, J.A., Stroup, T.S., McEvoy, J.P., Swartz, M.S., Rosenheck, R.A., Perkins, D.O., Keefe, R.S., Davis, S.M., Davis, C.E., Lebowitz, B.D., Severe, J. and Hsiao, J.K. (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 353, 1209-1223.PubMedGoogle Scholar
  75. Lipska, B.K., Lerman, D.N., Khaing, Z.Z., Weickert, C.S. and Weinberger, D.R. (2003) Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs. Eur J Neurosci. 18, 391-402.PubMedGoogle Scholar
  76. Lisman, J.E. and Grace, A.A. (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron. 46, 703-713.PubMedGoogle Scholar
  77. Luby, E.D., Cohen, B.D., Rosenbaum, G., Gottlieb, J.S. and Kelley, R. (1959) Study of a new schizophrenomimetic drug; sernyl. AMA Arch Neurol Psychiatry. 81, 363-369.PubMedGoogle Scholar
  78. Malhotra, A.K., Pinals, D.A., Weingartner, H., Sirocco, K., Missar, C.D., Pickar, D. and Breier, A. (1996) NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology. 14, 301-307.PubMedGoogle Scholar
  79. Malla, A. and Payne, J. (2005) First-episode psychosis: psychopathology, quality of life, and functional outcome. Schizophr Bull. 31, 650-671.PubMedGoogle Scholar
  80. Manoach, D.S. (2003) Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res. 60, 285-298.PubMedGoogle Scholar
  81. Manoach, D.S., Press, D.Z., Thangaraj, V., Searl, M.M., Goff, D.C., Halpern, E., Saper, C.B. and Warach, S. (1999) Schizophrenic subjects activate dorsolateral prefrontal cortex dur-ing a working memory task, as measured by fMRI. Biol Psychiatry. 45, 1128-1137.PubMedGoogle Scholar
  82. Manoach, D.S., Gollub, R.L., Benson, E.S., Searl, M.M., Goff, D.C., Halpern, E., Saper, C.B. and Rauch, S.L. (2000) Schizophrenic subjects show aberrant fMRI activation of dorso-lateral prefrontal cortex and basal ganglia during working memory performance. Biol Psy-chiatry. 48, 99-109.Google Scholar
  83. Marshall, M., Lewis, S., Lockwood, A., Drake, R., Jones, P. and Croudace, T. (2005) Associa-tion between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry. 62, 975-983.PubMedGoogle Scholar
  84. McEvoy, J.P., Lieberman, J.A., Stroup, T.S., Davis, S.M., Meltzer, H.Y., Rosenheck, R.A., Swartz, M.S., Perkins, D.O., Keefe, R.S., Davis, C.E., Severe, J. and Hsiao, J.K. (2006) Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 163, 600-610.PubMedGoogle Scholar
  85. Millar, J.K., Pickard, B.S., Mackie, S., James, R., Christie, S., Buchanan, S.R., Malloy, M.P., Chubb, J.E., Huston, E., Baillie, G.S., Thomson, P.A., Hill, E.V., Brandon, N.J., Rain, J.C., Camargo, L.M., Whiting, P.J., Houslay, M.D., Blackwood, D.H., Muir, W.J. and Porteous, D.J. (2005) DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science. 310, 1187-1191.PubMedGoogle Scholar
  86. Mishara, A.L. and Goldberg, T.E. (2004) A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book. Biol Psychiatry. 55, 1013-1022.PubMedGoogle Scholar
  87. Miyakawa, T., Leiter, L.M., Gerber, D.J., Gainetdinov, R.R., Sotnikova, T.D., Zeng, H., Caron, M.G. and Tonegawa, S. (2003) Conditional calcineurin knockout mice exhibit mul-tiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci USA. 100, 8987-8992.PubMedGoogle Scholar
  88. Moghaddam, B. (2003) Bringing order to the glutamate chaos in schizophrenia. Neuron. 40, 881-884.PubMedGoogle Scholar
  89. Moghaddam, B. and Adams, B.W. (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science. 281, 1349-1352.PubMedGoogle Scholar
  90. Monyer, H., Burnashev, N., Laurie, D.J., Sakmann, B. and Seeburg, P.H. (1994) Developmen-tal and regional expression in the rat brain and functional properties of four NMDA recep-tors. Neuron. 12, 529-540.PubMedGoogle Scholar
  91. Ninan, I., Jardemark, K.E. and Wang, R.Y. (2003) Olanzapine and clozapine but not haloperidol reverse subchronic phencyclidine-induced functional hyperactivity of N-methyl-D-aspartate receptors in pyramidal cells of the rat medial prefrontal cortex. Neuropharmacology. 44, 462-472.PubMedGoogle Scholar
  92. O’Donnell, P., Lewis, B.L., Weinberger, D.R. and Lipska, B.K. (2002) Neonatal hippocampal damage alters electrophysiological properties of prefrontal cortical neurons in adult rats. Cereb Cortex. 12, 975-982.PubMedGoogle Scholar
  93. Olney, J.W. and Farber, N.B. (1995) Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 52, 998-1007.PubMedGoogle Scholar
  94. Paus, T., Zijdenbos, A., Worsley, K., Collins, D.L., Blumenthal, J., Giedd, J.N., Rapoport, J.L. and Evans, A.C. (1999) Structural maturation of neural pathways in children and adoles-cents: in vivo study. Science. 283, 1908-1911.PubMedGoogle Scholar
  95. Paz, R.D., Andreasen, N.C., Daoud, S.Z., Conley, R., Roberts, R., Bustillo, J. and Perrone-Bizzozero, N.I. (2006) Increased expression of activity-dependent genes in cerebellar glu-tamatergic neurons of patients with schizophrenia. Am J Psychiatry. 163, 1829-1831.PubMedGoogle Scholar
  96. Perkins, D.O., Gu, H., Boteva, K. and Lieberman, J.A. (2005) Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry. 162, 1785-1804.PubMedGoogle Scholar
  97. Pillai, A., Terry, A.V., Jr. and Mahadik, S.P. (2006) Differential effects of long-term treatment with typical and atypical antipsychotics on NGF and BDNF levels in rat striatum and hip-pocampus. Schizophr Res. 82, 95-106.PubMedGoogle Scholar
  98. Rabinowitz, J., De Smedt, G., Harvey, P.D. and Davidson, M. (2002) Relationship between premorbid functioning and symptom severity as assessed at first episode of psychosis. Am J Psychiatry. 159, 2021-2026.PubMedGoogle Scholar
  99. Reichenberg, A., Weiser, M., Rapp, M.A., Rabinowitz, J., Caspi, A., Schmeidler, J., Knobler, H.Y., Lubin, G., Nahon, D., Harvey, P.D. and Davidson, M. (2005) Elaboration on premorbid intellectual performance in schizophrenia: premorbid intellectual decline and risk for schizophrenia. Arch Gen Psychiatry. 62, 1297-1304.PubMedGoogle Scholar
  100. Rosenheck, R. (2006) Integration of mental health care and supported employment. Am J Psychiatry. 163, 940; author reply 940.PubMedGoogle Scholar
  101. Rothman, D.L., Sibson, N.R., Hyder, F., Shen, J., Behar, K.L. and Shulman, R.G. (1999) In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics. Philos Trans R Soc Lond B Biol Sci. 354, 1165-1177.PubMedGoogle Scholar
  102. Rowland, L.M., Bustillo, J.R., Mullins, P.G., Jung, R.E., Lenroot, R., Landgraf, E., Barrow, R., Yeo, R., Lauriello, J. and Brooks, W.M. (2005) Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study. Am J Psychiatry. 162, 394-396.PubMedGoogle Scholar
  103. Rund, B.R., Melle, I., Friis, S., Larsen, T.K., Midboe, L.J., Opjordsmoen, S., Simonsen, E., Vaglum, P. and McGlashan, T. (2004) Neurocognitive dysfunction in first-episode psy-chosis: correlates with symptoms, premorbid adjustment, and duration of untreated psy-chosis. Am J Psychiatry. 161, 466-472.PubMedGoogle Scholar
  104. Rycroft, B.K. and Gibb, A.J. (2004) Inhibitory interactions of calcineurin (phosphatase 2B) and calmodulin on rat hippocampal NMDA receptors. Neuropharmacology. 47, 505-514.PubMedGoogle Scholar
  105. Sawaguchi, T. and Goldman-Rakic, P.S. (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.PubMedGoogle Scholar
  106. Shaw, P., Sporn, A., Gogtay, N., Overman, G.P., Greenstein, D., Gochman, P., Tossell, J.W., Lenane, M. and Rapoport, J.L. (2006) Childhood-onset schizophrenia: a double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 63, 721-730.PubMedGoogle Scholar
  107. Smith, K.E., Gibson, E.S. and Dell’Acqua, M.L. (2006) cAMP-dependent protein kinase postsynaptic localization regulated by NMDA receptor activation through translocation of an A-kinase anchoring protein scaffold protein. J Neurosci. 26, 2391-2402.PubMedGoogle Scholar
  108. Sowell, E.R., Peterson, B.S., Thompson, P.M., Welcome, S.E., Henkenius, A.L. and Toga, A.W. (2003) Mapping cortical change across the human life span. Nat Neurosci. 6, 309-315.PubMedGoogle Scholar
  109. Tarazi, F.I., Tomasini, E.C. and Baldessarini, R.J. (1999) Postnatal development of dopamine D1-like receptors in rat cortical and striatolimbic brain regions: an autoradiographic study. Dev Neurosci. 21, 43-49.PubMedGoogle Scholar
  110. Tauscher, J., Hussain, T., Agid, O., Verhoeff, N.P., Wilson, A.A., Houle, S., Remington, G., Zipursky, R.B. and Kapur, S. (2004) Equivalent occupancy of dopamine D1 and D2 recep-tors with clozapine: differentiation from other atypical antipsychotics. Am J Psychiatry. 161, 1620-1625.PubMedGoogle Scholar
  111. Theberge, J., Bartha, R., Drost, D.J., Menon, R.S., Malla, A., Takhar, J., Neufeld, R.W., Rogers, J., Pavlosky, W., Schaefer, B., Densmore, M., Al-Semaan, Y. and Williamson, P.C. (2002) Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry. 159, 1944-1946.PubMedGoogle Scholar
  112. Tibbo, P., Hanstock, C., Valiakalayil, A. and Allen, P. (2004) 3-T proton MRS investigation of glutamate and glutamine in adolescents at high genetic risk for schizophrenia. Am J Psychiatry. 161, 1116-1118.PubMedGoogle Scholar
  113. Tseng, K.Y. and O’Donnell, P. (2004) Dopamine-glutamate interactions controlling prefrontal cortical pyramidal cell excitability involve multiple signaling mechanisms. J Neurosci. 24, 5131-5139.PubMedGoogle Scholar
  114. Tseng, K.Y. and O’Donnell, P. (2005) Post-pubertal emergence of prefrontal cortical up states induced by D1-NMDA co-activation. Cereb Cortex. 15, 49-57.PubMedGoogle Scholar
  115. Tseng, K.Y. and O’Donnell, P. (2007) Dopamine Modulation of Prefrontal Cortical Interneu-rons Changes during Adolescence. Cereb Cortex. 17, 1235-1240.PubMedGoogle Scholar
  116. Tseng, K.Y., Mallet, N., Toreson, K.L., Le Moine, C., Gonon, F. and O’Donnell, P. (2006a) Excitatory response of prefrontal cortical fast-spiking interneurons to ventral tegmental area stimulation in vivo. Synapse. 59, 412-417.PubMedGoogle Scholar
  117. Tseng, K.Y., Amin, F., Lewis, B.L. and O’Donnell, P. (2006b) Altered prefrontal cortical metabolic response to mesocortical activation in adult animals with a neonatal ventral hip-pocampal lesion. Biol Psychiatry. 60, 585-590.PubMedGoogle Scholar
  118. Tseng, K.Y., Lewis, B.L. Lipska, B.K. and O’Donnell, P. (2007) Post-pubertal disruption of medical prefrontal cortical dopamine-glutamate interactions in a developmental animal model of schizophrenia. Biol. Psychiatry. Jan 2; [Epub ahead of print]Google Scholar
  119. Volavka, J., Czobor, P., Cooper, T.B., Sheitman, B., Lindenmayer, J.P., Citrome, L., McEvoy, J.P. and Lieberman, J.A. (2004) Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. J Clin Psychiatry. 65, 57-61.PubMedGoogle Scholar
  120. Webster, M.J., Weickert, C.S., Herman, M.M. and Kleinman, J.E. (2002) BDNF mRNA expression during postnatal development, maturation and aging of the human prefrontal cortex. Brain Res Dev Brain Res. 139, 139-150.PubMedGoogle Scholar
  121. Weinberger, D.R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 44, 660-669.PubMedGoogle Scholar
  122. Weiser, M., Reichenberg, A., Rabinowitz, J., Kaplan, Z., Mark, M., Bodner, E., Nahon, D. and Davidson, M. (2001) Association between nonpsychotic psychiatric diagnoses in adoles-cent males and subsequent onset of schizophrenia. Arch Gen Psychiatry. 58, 959-964.PubMedGoogle Scholar
  123. Wiersma, D., Wanderling, J., Dragomirecka, E., Ganev, K., Harrison, G., An Der Heiden, W., Nienhuis, F.J. and Walsh, D. (2000) Social disability in schizophrenia: its development and prediction over 15 years in incidence cohorts in six European centres. Psychol Med. 30, 1155-1167.PubMedGoogle Scholar
  124. Williams, K., Russell, S.L., Shen, Y.M. and Molinoff, P.B. (1993) Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron. 10, 267-278.PubMedGoogle Scholar
  125. Wyatt, R.J. (1991) Neuroleptics and the natural course of schizophrenia. Schizophr Bull. 17, 325-351.PubMedGoogle Scholar
  126. Zahrt, J., Taylor, J.R., Mathew, R.G. and Arnsten, A.F. (1997) Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory per-formance. J Neurosci. 17, 8528-8535.PubMedGoogle Scholar
  127. Zecevic, N., Bourgeois, J.P. and Rakic, P. (1989) Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. Brain Res Dev Brain Res. 50, 11-32.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Rodrigo D. Paz
    • 1
  • Kuei-Yuan Tseng
    • 2
  1. 1.Department of Psychiatry & NeuroscienceUniversidad Diego PortalesChile
  2. 2.Department of Cellular & Molecular PharmacologyRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA

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