From the concept of "antipsychotic" to that of "multidimensional normostabilizer": The clinical-therapeutic itinerary of schizophrenia;Dal concetto di antipsicotico a quello di "normostabilizzatore multidimensionale": Il percorso clinico-terapeutico della schizofrenia

Italian Journal of Psychopathology

Volumn 16, Issue 1, 2010, Pages 87-103

  Altamura, Alfredo Carlo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Atypical antipsychotics; Dopamine receptors; Glutamatergic system; Neurobiological theories; Phase related symptomatology; Schizophrenia

Indexed keywords

4 AMINOBUTYRIC ACID; DOPAMINE 2 RECEPTOR BLOCKING AGENT; NEUROLEPTIC AGENT; NEUROTRANSMITTER; SEROTONIN;

ACUTE DISEASE; CENTRAL NERVOUS SYSTEM; CLONAL ANERGY; CONTROLLED STUDY; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DOPAMINERGIC ACTIVITY; DYSMETRIA; HUMAN; NEGATIVE SYNDROME; NEUROCHEMISTRY; POSITIVE SYNDROME; POSITRON EMISSION TOMOGRAPHY; REVIEW; SCHIZOPHRENIA;

EID: 77952992661     PISSN: 15921107     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (141)

1. 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
2. Delay J, Deniker P, Harl J. Traitment des états d'excitation et d'agitation par une méthode medicamenteuse derivée de l'hibernotherapie. Ann Med Psychol 1952;110:267-273
3. Altamura AC, Guercetti G, Invernizzi G. Eterogeneità etiopatogenetica della schizofrenia: nuove evidenze, possibili modelli teorici ed ipotesi terapeutiche. Rivista di Psichiatria 1987;22:1-21.
4. Bleuler E. Dementia praecox oder die Gruppe der Schizofrenien. In: Aschaffenburg G, editor. Handbuch der psychiatrie. Vienna: Leipzig 1911-1928.
5. Arieti S. Some aspects of the psychopathology of schizophrenia. Am J Psychother 1954;8:396-414.
6. Cooper B. Social class and prognosis in schizophrenia. I. Br J Med Psychol 1961;34:157-162
7. Cooper B. Social class and prognosis in schizophrenia. II. Br J Prev Soc Med 1961;15:31-41.
8. Schneider K. Klinische psychopathologie. Stuttgart: Thieme Verlag 1955.
9. Snyder SH, Aghajanian GK, Matthysse S. Prospects for research on schizophrenia. V. Pharmacological observations, drug-induced psychoses. Neurosci Res Program Bull 1972;10:430-445
10. Snyder SH. Catecholamines in the brain as mediators of amphetamine psychosis. Arch Gen Psychiatry 1972; 27:169-179
11. Seeman P, Lee T, Chau-Wong M, Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976;261:717-719
12. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des 2009;15:2550-2559
13. Van Os J, Kapur S. Schizophrenia. Lancet 2009;374:635-645
14. Altamura AC, Bobo WV, Meltzer HY. Factors affecting outcome in schizophrenia and their relevance for psychopharmacological treatment. Int Clin Psychopharmacol 2007;22:249-267
15. Baaré WF, van Oel CJ, Hulshoff Pol HE, Schnack HG, Durston S, et al. S. Volumes of brain structures in twins discordant for schizophrenia. Arch Gen Psychiatry 2001;58:33-40.
16. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Möller HJ. WFSBP Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia. Part 1: acute treatment of schizophrenia. World J Biol Psychiatry 2005;6:132-191
17. Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Möller HJ. WFSBP Task Force on Treatment Guidelines for Schizophrenia. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: long-term treatment of schizophrenia. World J Biol Psychiatry 2006;7:5-40.
18. Tan HY, Callicott JH, Weinberger DR. Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cereb Cortex 2007;17:S171-81.
19. Csernansky JG, Bardgett ME. Limbic-cortical neuronal damage and the pathophysiology of schizophrenia. Schizophr Bull 1998;24:231-248
20. Montgomery SA, van Zwieten-Boot B. ECNP Consensus meeting. Negative, depressive and cognitive symptoms of schizophrenia. Nice, March 2004. Eur Neuropsychopharmacol 2007;17:70-77
21. Mehler-Wex C, Riederer P, Gerlach M. Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson's disease, schizophrenia and attention deficit hyperactivity disorder. Neurotox Res 2006;10:167-179
22. Meltzer HY, Li Z, Kaneda Y, Ichikawa J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27:1159-1172
23. Peroutka SJ. Serotonin receptor variants in disease: new therapeutic opportunities? Ann N Y Acad Sci 1998; 861:16-25.
24. Royston MC, Simpson MDC. Post mortem chemistry of schizophrenia. In: Kerwin R, Dawbarn D, Mc Culloch J, Tamminga C, editora. Neurobilogy in psychiatry. Cambridge: Cambridge University Press 1991, pp. 1-14.
25. Seeman P. Glutamate and dopamine components in schizophrenia. J Psychiatry Neurosci 2009 34:143-149
26. Wassef A, Baker J, Kochan LD. GABA and schizophrenia: a review of basic science and clinical studies. J Clin Psychopharmacol 2003; 23:601-640
27. Javitt DC. Glycine modulators in schizophrenia. Curr Opin Investig Drugs 2002;3:1067-1072
28. Coyle JT. Substance use disorders and schizophrenia: a question of shared glutamatergic mechanisms. Neurotox Res 2006;10-221-233
29. Binder EB, Kinkead B, Owens MJ, Nemeroff CB. The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs. Biol Psychiatry 2001;50:856-872
30. Sim K, Yang GL, Loh D, Poon LY, Sitoh YY, Verma S, et al. White matter abnormalities and neurocognitive deficits associated with the passivity phenomenon in schizophrenia: a diffusion tensor imaging study. Psychiatry Res 2009;172:121-127
31. Koutsouleris N, Gaser C, Jäger M, Bottlender R, Frodl T, Holzinger S, et al. Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study. Neuroimage 2008;39:1600-1612
32. Fornito A, Yücel M, Pantelis C. Reconciling neuroimaging and neuropathological findings in schizophrenia and bipolar disorder. Curr Opin Psychiatry 2009;22:312-319
33. Borgwardt SJ, McGuire PK, Aston J, Berger G, Dazzan P, Gschwandtner U, et al. Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis. Br J Psychiatry Suppl 2007;51:S69-75.
34. Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ, et al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 2003;361:281-288
35. Sun D, Stuart GW, Jenkinson M, Wood SJ, McGorry PD, Velakoulis D, et al. Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Mol Psychiatry 2009;14:976-986
36. Farrow TF, Whitford TJ, Williams LM, Gomes L, Harris AW. Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder. Biol Psychiatry 2005;58:713-723
37. Whitford TJ, Grieve SM, Farrow TF, Gomes L, Brennan J, Harris AW, et al. Progressive grey matter atrophy over the first 2-3 years of illness in first-episode schizophrenia: a tensor-based morphometry study. Neuroimage 2006;32:511-519
38. Koo MS, Levitt JJ, Salisbury DF, Nakamura M, Shenton ME, McCarley RW. A cross-sectional and longitudinal magnetic resonance imaging study of cingulate gyrus gray matter volume abnormalities in first-episode schizophrenia and first-episode affective psychosis. Arch Gen Psychiatry 2008; 65:746-760
39. Lieberman JA, Tollefson GD, Charles C, Zipursky R, Sharma T, Kahn RS, et al. HGDH Study Group. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005;62:361-370
40. Kanahara N, Shimizu E, Sekine Y, Uchida Y, Shibuya T, Yamanaka H, et al. Does hypofrontality expand to global brain area in progression of schizophrenia? A cross-sectional study between first-episode and chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:410-415
41. Murray RM, Lappin J, Di Forti M. Schizophrenia: from developmental deviance to dopamine dysregulation. Eur Neuropsychopharmacol 2008;18:S129-34.
42. Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull 2009;35:528-548
43. Parellada E, Lomena F, Font M, Pareto D, Gutierrez F, Simo M, et al. Fluordeoxyglucose-PET study in first-episode schizophrenic patients during the hallucinatory state, after remission and during linguistic-auditory activation. Nucl Med Commun 2008;29:894-900.
44. Park IH, Kim JJ, Chun J, Jung YC, Seok JH, Park HJ, Lee JD. Medial prefrontal default-mode hypoactivity affecting trait physical anhedonia in schizophrenia. Psychiatry Res 2009;171:155-165
45. Andreasen NC. The American concept of schizophrenia. Schizophr Bull 1989; 15:519-531
46. van Os J, Murray R. Gene-environment interactions in schizophrenia. Introduction. Schizophr Bull 2008;34:1064-1065
47. Stip E, Letourneau G. Psychotic symptoms as a continuum between normality and pathology. Can J Psychiatry 2009;54:140-151
48. Eaton WW, Romanoski A, Anthony JC, Nestadt G. Screening for psychosis in the general population with a self-report interview. J Nerv Ment Dis 1991;179:689-693
49. Van Os J, Hanssen M, Bijl RV, Ravelli A. Strauss (1969) revisited: a psychosis continuum in the general population? Schizophr Res 2000;45:11-20.
50. King M, Nazroo J, Weich S, McKenzie K, Bhui K, Karlsen S, et al. Psychotic symptoms in the general population of England - a comparison of ethnic groups (The EMPIRIC study). Soc Psychiatry Psychiatr Epidemiol 2005;40:509.
51. Perälä J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsä E, Pirkola S, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007;64:19-28.
52. Gruzelier J, Richardson A. Patterns of cognitive asymmetry and psychosis proneness. Int J Psychophysiol 1994;18:217-225
53. Chapman JP, Kwapil TR, Eckblad M, Chapman LJ. Putatively psychosis-prone subjects 10 years later. J Abnorm Psychol 1994;103:171-183
54. Hanssen M, Bak M, Bijl R, Vollebergh W, van Os J. The incidence and outcome of subclinical psychotic experiences in the general population. Br J Clin Psychol 2005,44:181-191
55. Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H. Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. Arch Gen Psychiatry 2000;57:1053-1058
56. Boks MP, Schipper M, Schubart CD, Sommer IE, Kahn RS, Ophoff RA. Investigating gene environment interaction in complex diseases: increasing power by selective sampling for environmental exposure. Int J Epidemiol 2007;36:1363-1369
57. Meehl PE. Schizotaxia, schizotypy, schizophrenia. American Psychologist 1962;17:827-838
58. Clarke MC, Tanskanen A, Huttunen M, Whittaker JC, Cannon M. Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia. Am J Psychiatry 2009;166:1025-1030
59. Van Os J, Castle DJ, Takei N, Der G, Murray RM. Psychotic illness in ethnic minorities: clarification from the 1991 census. Psychol Med 1996;26:203-208
60. Peralta V, Cuesta MJ, Giraldo C, Cardenas A, Gonzalez F. Classifying psychotic disorders: issues regarding categorial vs. dimensional approaches and time frame to assess symptoms. Eur Arch Psychiatry Clin Neurosci 2002;252:12-18
61. Bilder RM, Goldman RS, Volavka J, Czobor P, Hoptman M, Sheitman B, et al. Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry 2002;159:1018-1028
62. Liddle PF. The symptoms of chronic schizophrenia. A re-examination of the positive-negative dichotomy. Br J Psychiatry 1987;151:145-151
63. Liddle PF. Syndromes of schizophrenia on factor analysis. Br J Psychiatry 1992;161:861.
64. Peralta V, Cuesta MJ, de Leon J. An empirical analysis of latent structures underlying schizophrenic symptoms: a four-syndrome model. Biol Psychiatry 1994;36:726-736
65. Salokangas RK. Structure of schizophrenic symptomatology and its changes over time: prospective factor-analytical study. Acta Psychiatr Scand 1997;95:32-39
66. Peralta V, Cuesta MJ. How many and which are the Psychopathological dimensions in schizophrenia? Issues influencing their ascertainment. Schizophr Res 2001;49:269-285
67. Lindenmayer JP, Grochowski S, Hyman RB. Five factor model of schizophrenia: replication across samples. Schizophr Res 1995;14:229-234
68. Lançon C, Auquier P, Nayt G, Reine G. Stability of the five-factor structure of the Positive and Negative Syndrome Scale (PANSS). Schizophr Res 2000;42:231-239
69. Gold JM. Cognitive deficits as treatment targets in schizophrenia. Schizophr Res 2004;72:21-28
70. Andreasen NC, Paradiso S, O'Leary DS. "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical- cerebellar circuitry? Schizophr Bull 1998;24:203-218
71. Cornblatt B, Obuchowski M, Roberts S, Pollack S, Erlenmeyer-Kimling L. Cognitive and behavioral precursors of schizophrenia. Dev Psychopathol 1999;11:487-508.
72. Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 1994;344:1398-1402
73. Niendam TA, Bearden CE, Rosso IM, Sanchez LE, Hadley T, Nuechterlein KH, et al. A prospective study of childhood neurocognitive functioning in schizophrenic patients and their siblings. Am J Psychiatry 2003;160:2060-2062
74. David AS, Malmberg A, Brandt L, Allebeck P, Lewis G. IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 1997;27:1311-1323
75. Reichenberg A, Weiser M, Rabinowitz J, Caspi A, Schmeidler J, Mark M, et al. A population-based cohort study of premorbid intellectual, language, and behavioral functioning in patients with schizophrenia, schizoaffective disorder, and nonpsychotic bipolar disorder. Am J Psychiatry 2002;159:2027-2035
76. Meltzer HY, Park S, Kessler R. Cognition, schizophrenia, and the atypical antipsychotic drugs. Proc Natl Acad Sci USA 1999; 96:13591-13593
77. Lysaker PH, Bell MD, Zito WS, Bioty SM. Social skills at work. Deficits and predictors of improvement in schizophrenia. J Nerv Ment Dis 1995;183:688-692
78. Lysaker P, Bell M. Work and meaning: disturbance of volition and vocational dysfunction in schizophrenia. Psychiatry 1995;58:392-400.
79. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153:321-330
80. Meltzer HY, Thompson PA, Lee MA, Ranjan R. Neuropsychologic deficits in schizophrenia: relation to social function and effect of antipsychotic drug treatment. Neuropsychopharmacology 1996; 14:S27-33.
81. Velligan DI, Mahurin RK, Diamond PL, Hazleton BC, Eckert SL, Miller AL. The functional significance of symptomatology and cognitive function in schizophrenia. Schizophr Res 1997;25:21-31.
82. Dazzan P, Lloyd T, Morgan KD, Zanelli J, Morgan C, Orr K, et al. Neurological abnormalities and cognitive ability in first-episode psychosis. Br J Psychiatry 2008;193:197-202.
83. Klingberg S, Wittorf A, Wiedemann G. Disorganization and cognitive impairment in schizophrenia: independent symptom dimensions? Eur Arch Psychiatry Clin Neurosci 2006; 256:532-540
84. Berman I, Viegner B, Merson A, Allan E, Pappas D, Green AI. Differential relationships between positive and negative symptoms and neuropsychological deficits in schizophrenia. Schizophr Res 1997;3:1-10.
85. Meltzer HY. Role of serotonin in the action of atypical antipsychotic drugs. Clin Neurosci 1995;3:64-75.
86. Harvey PD, Keefe RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001;158:176-184
87. Friedman JI, Temporini H, Davis KL. Pharmacologic strategies for augmenting cognitive performance in schizophrenia. Biol Psychiatry 1999;45:1-16.
88. Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DA, et al. The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone. Biol Psychiatry 2002;51:972-978
89. Purdon SE. Cognitive improvement in schizophrenia with novel antipsychotic medications. Schizophr Res 1999;35:S51-60.
90. Altamura AC, Guercetti G, Percudani M. Dexamethasone suppression test in negative and positive schizophrenia. Psychiatry Res 1989;30:69-75.
91. Altamura AC, Mauri MC, Cavallaro R, Gorni A. Haloperidol metabolism and antipsychotic effect in schizophrenia. Lancet 1987;1:814-815
92. Crow TJ. Brain changes and negative symptoms in schizophrenia. Psychopathology 1995; 28:18-21.
93. Meltzer HY. Clozapine: is another view valid? Am J Psychiatry 1995;152:821-825
94. Meltzer HY, Matsubara S, Lee JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther 1989; 251:238-246
95. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry 2002;47:27-38.
96. Altamura AC. Novel antipsychotics and the problem of clinical stabilization in schizophrenia: are they "stabilizer" rather than typical compounds? Int Clin Psychopharmacol 1996;11:153-155
97. Kane JM. The current status of neuroleptic therapy. J Clin Psychiatry 1989;50:322-328
98. Percudani M, Fattore G, Galletta J, Mita PL, Contini A, Altamura AC. Health care costs of therapy-refractory schizophrenic patients treated with clozapine: a study in a community psychiatric service in Italy. Acta Psychiatr Scand 1999;99:274-280
99. Green MF, Marshall BD Jr, Wirshing WC, Ames D, Marder SR, McGurk S, et al. Does risperidone improve verbal working memory in treatment-resistant schizophrenia? Am J Psychiatry 1997;154:799-804.
100. Hagger C, Buckley P, Kenny JT, Friedman L, Ubogy D, Meltzer HY. Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 1993;34:702-712
101. Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the "right stuff"? Schizophr Bull 2000;26:119-136
102. Breier A. Clozapine and noradrenergic function: support for a novel hypothesis for superior efficacy. J Clin Psychiatry 1994; 55:S122-5.
103. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-1223
104. Potkin SG, Weiden PJ, Loebel AD, Warrington LE, Watsky EJ, Siu CO. Remission in schizophrenia: 196-week, double-blind treatment with ziprasidone vs. haloperidol. Int J Neuropsychopharmacol 2009;12:1233-1248
105. Meltzer HY, Sumiyoshi T. Does stimulation of 5-HT(1A) receptors improve cognition in schizophrenia? Behav Brain Res 2008;195:98-102.
106. Kern RS, Green MF, Cornblatt BA, Owen JR, McQuade RD, Carson WH, et al. The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology (Berl) 2006;187:312-320
107. Harvey PD, Rabinowitz J, Eerdekens M, Davidson M. Treatment of cognitive impairment in early psychosis: a comparison of risperidone and haloperidol in a large long-term trial. Am J Psychiatry 2005;162:1888-1895
108. Meltzer HY, McGurk SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 1999;25:233-255
109. Velligan DI, Newcomer J, Pultz J, Csernansky J, Hoff AL, Mahurin R, et al. Does cognitive function improve with quetiapine in comparison to haloperidol? Schizophr Res 2002;53:239-248
110. Altamura AC, Mundo E, Bassetti R, Green A, Lindenmayer JP, Alphs L, et al. Transcultural differences in suicide attempters: analysis on a high-risk population of patients with schizophrenia or schizoaffective disorder. Schizophr Res 2007;89:140-146
111. Patterson TL, Leeuwenkamp OR. Adjunctive psychosocial therapies for the treatment of schizophrenia. Schizophr Res 2008;100:108-119
112. McGorry PD. Psychoeducation in first-episode psychosis: a therapeutic process. Psychiatry 1995;58:313-28.
113. Leucht S, Lasser R. The concepts of remission and recovery in schizophrenia. Pharmacopsychiatry 2006;39:161-170
114. Zygmunt A, Olfson M, Boyer CA, Mechanic D. Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 2002;159:1653-1664
115. Chue P. The assessment and management of antipsychotic-associated metabolic disturbances from a psychiatric perspective. Can J Psychiatry 2004;49:200-207
116. Naber D, Karow A, Lambert M. Subjective well-being under the neuroleptic treatment and its relevance for compliance. Acta Psychiatr Scand 2005;427:S29-34.
117. van Os J, Altamura AC, Bobes J, Owens DC, Gerlach J, Hellewell JS, et al. 2-COM: an instrument to facilitate patient-professional communication in routine clinical practice. Acta Psychiatr Scand 2002;106:446-452
118. Van Os J, Altamura AC, Bobes J, Gerlach J, Hellewell JS, Kasper S, et al. Evaluation of the Two-Way Communication Checklist as a clinical intervention. Results of a multinational, randomised controlled trial. Br J Psychiatry 2004;184:79-83.
119. Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, et al. Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 2008;165:1040-1047
120. Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, et al. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry 2008;165:1585-1593
121. Shekhar A, Potter WZ, Lightfoot J, Lienemann J, Dubé S, Mallinckrodt C, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry 2008;165:1033-1039
122. Meltzer HY, Arvanitis L. Bauer D, Rein W. Placebo controlled evluation of four novel compounds for the treatment of schizophrenia and schizoaffective disorder. Am J Psychiatry 2004;161:975-984
123. Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry 1993;150:1731-1733
124. Moghaddam B, Adams BW. Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 1998;281:1349-1352
125. Gao XM, Sakai K, Roberts RC, Conley RR, Dean B, Tamminga CA. Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia. Am J Psychiatry 2000;157:1141-1149
126. Chose S, Gleason KA, Potts BW, Lewis-Amezcua K, Tamminga CA. Differential expression of metabotropic glutamate receptors 2 and 3 in schizophrenia: a mechanism for antipsychotic drug action? Am J Psychiatry 2009;166:812-820
127. Rorick-Kehn LM, Johnson BG, Knitowski KM, Salhoff CR, Witkin JM, Perry KW,et al. In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders. Psychopharmacology (Berl) 2007;193:121-136
128. Kim DH, Maneen MJ, Stahl SM. Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia. Neurotherapeutics 2009;6:78-85.
129. Javitt D.C. Is the glycine site half saturated or half unsaturated? Effects of glutamatergic drugs in schizophrenia patients. Curr Opin Psychiatry 2006;19:151-157
130. Litman RE, Su TP, Potter WZ, Hong WW, Pickar D. Idazoxan and response to typical neuroleptics in treatment-resistant schizophrenia. Comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 1996;168:571-579
131. Marcus MM, Jardemark KE, Wadenberg ML, Langlois X, Hertel P, Svensson TH. Combined alpha2 andD2/3 receptor blockade enhances cortical glutamatergic transmission and reverses cognitive impairment in the rat. Int J Neuropsychopharmacol 2005;8:315-327
132. Bishara D, Taylor D. Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. Drugs 2008;68:2269-2292
133. Altamura AC, Mundo E, Dell'Osso B, Tacchini G, Buoli M, et al. Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: a 4-year follow-up naturalistic study. J Affect Disord 2008;110:135-141
134. Cahn W, Rais M, Stigter FP, van Haren NE, Caspers E, Hulshoff Pol HE, et al. Psychosis and brain volume changes during the first five years of schizophrenia. Eur Neuropsychopharmacol 2009; 19:147-151
135. Moorhead TW, McKirdy J, Sussmann JE, Hall J, Lawrie SM, Johnstone EC, et al. Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry. 2007;62:894-900.
136. Strakowski SM, DelBello MP, Zimmerman ME, Getz GE, Mills NP, Ret J, et al. Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder. Am J Psychiatry 2002;159:1841-1847
137. Altamura AC, Mauri MC, Guercetti G, Cazzullo CL. Fluphenazine decantate in acute and maintenance therapy of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 1987;11:613-623
138. Carlsson A, Hansson LO, Waters N, Carlsson ML. A glutamatergic deficiency model of schizophrenia. Br J Psychiatry Suppl 1999;37:2-6.
139. Altamura AC. A multidimensional (pharmacokinetic and clinical-biological) approach to neuroleptic response in schizophrenia. With particular reference to drug resistance. Schizophr Res 1993;8:187-198
140. Altamura AC, Boin F, Maes M. HPA axis and cytokines dysregulation in schizophrenia: potential implications for the antipsychotic treatment. Eur Neuropsychopharmacol 1999;10:1-4.
141. Altamura AC, Glick ID. Designing outcome studies to determine efficacy and safety of antipsychotics for "real world" treatment of schizophrenia. Int J Neuropsychopharmacol 2010; in press.