Phenotype of schizophrenia: a review and formulation (original) (raw)

• Tamminga CA . Development in somatic treatments. Am J Psychiatry 1994; 151: 216–219.
  Article PubMed Google Scholar
• Delay J, Deniker P, Harl J-M . Traitement de etats d'excitation et d'agitation par une methode medicamenteuse derivee de l'hibernotherapie. Ann Med Psychol 1952; 110: 267–273.
  CAS Google Scholar
• Carlsson A, Lindquist M . Effect of chlorpromazine and haloperidol of formation of 3- methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 1963; 20: 140–144.
  Article CAS Google Scholar
• Davis JM . Review of antipsychotic drug literature. In: Klein DF, Davis JM (eds). Diagnosis and Drug Treatment of Psychiatric Disorders. The Williams and Wilkins Company: Baltimore, 1969 pp 52–138.
  Google Scholar
• Liddle PF . The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. Br J Psychiatry 1987; 151: 145–151.
  Article CAS PubMed Google Scholar
• Carpenter Jr WT, Buchanan RW . Domains of psychopathology relevant to the study of etiology and treatment in schizophrenia. In: Schulz SC, Tamminga CA (eds). Schizophrenia: Scientific Progress. Oxford University Press: New York, NY, 1989 pp 13–22.
  Google Scholar
• Kay SR, Sevy S . Pyramidical model of schizophrenia. Schizophr Bull 1990; 16: 537–545.
  Article CAS PubMed Google Scholar
• Arndt S, Alliger RJ, Andreasen NC . The distinction of positive and negative symptoms. The failure of a two-dimensional model. Br J Psychiatry 1991; 158: 317–322.
  Article CAS PubMed Google Scholar
• Lenzenweger MF, Dworkin RH, Wethington E . Examining the underlying structure of schizophrenic phenomenology: evidence for a three-process model. Schizophr Bull 1991; 17: 515–524.
  Article CAS PubMed Google Scholar
• Barnes TR, Liddle PF . Evidence for the validity of negative symptoms [Review]. Mod Probl Pharmacopsychiatry 1990; 24: 43–72.
  Article CAS PubMed Google Scholar
• Andreasen NC, Arndt S, Alliger RJ, Miller D, Flaum M . Symptoms of schizophrenia. Methods, meanings, and mechanisms. Arch Gen Psychiatry 1995; 52: 341–351.
  Article CAS PubMed Google Scholar
• Ciompi L, Muller C . Lifestyle and age of schizophrenics. A catamnestic long-term study into old age. (German). Monographien aus dem Gesamtgebiete der Psychiatrie. Psychiatry Series 1976 vol. 1, pp 1–242.
  Google Scholar
• Bleuler M . The Schizophrenic Disorders: Long-Term Patient and Family Studies. Yale University Press: New Haven, CT, 1978.
  Google Scholar
• Lieberman JA . Pathophysiologic mechanisms in the pathogenesis and clinical course of schizophrenia. J Clin Psychiatry 1999; 60(Suppl 12): 9–12.
  PubMed Google Scholar
• Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A . The Vermont longitudinal study of persons with severe mental illness, I: Methodology, study sample, and overall status 32 years later. Am J Psychiatry 1987; 144: 718–726.
  Article CAS PubMed Google Scholar
• Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A . The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. Am J Psychiatry 1987; 144: 727–735.
  Article CAS PubMed Google Scholar
• Huber G, Gross G, Schuttler R . Schizophrenie: Verlaufs und socialpsychiatrische langzeit unter suchungen an den 1945 bis 1959 in Bonn hospitalisierten schizophrenen Kranken. Monographien aus dem Gesamtgebiete der Psychiatrie 1979; Bd 21.
• Tsuang MT, Woolson RF, Fleming JA . Long-term outcome of major psychoses.I. Schizophrenia and affective disorders compared with psychiatrically symptom-free surgical conditions. Arch Gen Psychiatry 1979; 36: 1295–1301.
  Article CAS PubMed Google Scholar
• Harvey PD, Bertisch H, Friedman JI, Marcus S, Parrella M, White L et al. The course of functional decline in geriatric patients with schizophrenia: cognitive-functional and clinical symptoms as determinants of change. Am J Geriatr Psychiatry 2003; 11: 610–619.
  PubMed Google Scholar
• Owen M, Williams N, O'Donovan M . The molecular genetics of schizophrenia: new findings promise new insights. Mol Psychiatry 2003; 9: 14–17.
  Article CAS Google Scholar
• Gottesman II, Gould T . The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160: 636–645.
  Article PubMed Google Scholar
• Kendell RE, Kemp IW . Maternal influenza in the etiology of schizophrenia [see comments]. Arch Gen Psychiatry 1989; 46: 878–882.
  Article CAS PubMed Google Scholar
• Barr CE, Mednick SA, Munk-Jorgensen P . Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study. Arch Gen Psychiatry 1990; 47: 869–874.
  Article CAS PubMed Google Scholar
• Mednick SA, Cannon TD . Fetal development, birth and the syndromes of adult schizophrenia. In: Mednick SA, Cannon TD, Barr CE, Lyon M (eds). Fetal Neural Development and Adult Schizophrenia. Cambridge University Press: New York, NY, 1991.
  Google Scholar
• O'Callaghan E, Sham P, Takei N, Glover G, Murray RM . Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic. Lancet 1991; 337: 1248–1250.
  Article CAS PubMed Google Scholar
• Chapman LJ, Chapman JP . Problems in the measurement of cognitive deficit. Psychol Bull 1973; 79: 380–385.
  Article CAS PubMed Google Scholar
• Gruzelier J, Seymour K, Wilson L, Jolley A, Hirsch S . Impairments on neuropsychologic tests of temporohippocampal and frontohippocampal functions and word fluency in remitting schizophrenia and affective disorders. Arch Gen Psychiatry 1988; 45: 623–629.
  Article CAS PubMed Google Scholar
• Goldberg TE, Ragland JD, Torrey EF, Gold JM, Bigelow LB, Weinberger DR . Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Arch Gen Psychiatry 1990; 47: 1066–1072.
  Article CAS PubMed Google Scholar
• Braff DL, Heaton R, Kuck J, Cullum M, Moranville J, Grant I et al. The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results. Arch Gen Psychiatry 1991; 48: 891–898.
  Article CAS PubMed Google Scholar
• Gur RC, Saykin AJ, Gur RE . Neuropsychological study of schizophrenia. Schizophr Res 1991; 1: 153–162.
  Google Scholar
• Liddle PF, Morris DL . Schizophrenic syndromes and frontal lobe performance. Br J Psychiatry 1991; 158: 340–345.
  Article CAS PubMed Google Scholar
• Gold J, Goldberg T, Weinberger D . Prefrontal function and schizophrenic symptoms. Neuropsychiat Neuropsychol Behav Neurol 1992; 5: 253–261.
  Google Scholar
• Sullivan EV, Shear PK, Zipursky RB, Sagar HJ, Pfefferbaum A . A deficit profile of executive, memory, and motor functions in schizophrenia [published erratum appears in Biol Psychiatry 1995 May 15;37(10):758–760]. Biol Psychiatry 1994; 36: 641–653.
  Article CAS PubMed Google Scholar
• Nuechterlein KH, Dawson ME, Gitlin M, Ventura J, Goldstein MJ, Snyder KS et al. Developmental processes in schizophrenic disorders: longitudinal studies of vulnerability and stress. Schizophr Bull 1992; 18: 387–425.
  Article CAS PubMed Google Scholar
• Saykin AJ, Gur RC, Gur RE, Mozley PD, Mozley LH, Resnick SM et al. Neuropsychological function in schizophrenia. Selective impairment in memory and learning. Arch Gen Psychiatry 1991; 48: 618–624.
  Article CAS PubMed Google Scholar
• Gold JM, Hermann BP, Randolph C, Wyler AR, Goldberg TE, Weinberger DR . Schizophrenia and temporal lobe epilepsy. A neuropsychological analysis. Arch Gen Psychiatry 1994; 51: 265–272.
  Article CAS PubMed Google Scholar
• Goldman-Rakic PS . Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 1994; 6: 348–357.
  Article CAS PubMed Google Scholar
• Avila MT, Hong E, Thaker GK . Current progress in schizophrenia research. Eye movement abnormalities in schizophrenia: what is the nature of the deficit? J Nerv Men Dis 2002; 190: 479–480.
  Article Google Scholar
• Ross RG, Olincy A, Mikulich SK, Radant AD, Harris JG, Waldo M et al. Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes. Psychophysiology 2002; 39: 809–819.
  Article PubMed Google Scholar
• Braff DL, Geyer MA . Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 1990; 47: 181–188.
  Article CAS PubMed Google Scholar
• Swerdlow NR, Geyer MA . Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 1998; 24: 285–301.
  Article CAS PubMed Google Scholar
• Freedman R . Electrophysiological phenotypes. Meth Mol Med 2003; 77: 215–225.
  Google Scholar
• Sweeney JA, Luna B, Srinivasagam NM, Keshavan MS, Schooler NR, Haas GL et al. Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields. Biol Psychiatry 1998; 44: 698–708.
  Article CAS PubMed Google Scholar
• Tregellas JR, Tanabe JL, Miller DE, Ross RG, Olincy A, Freedman R . Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study. Am J Psychiatry 2004; 161: 315–321.
  Article PubMed Google Scholar
• Thaker GK, Ross DE, Cassady SL, Adami HM, Medoff DR, Sherr J . Saccadic eye movement abnormalities in relatives of patients with schizophrenia. Schizophr Res 2000; 45: 235–244.
  Article CAS PubMed Google Scholar
• Thaker GK, Nguyen JA, Tamminga CA . Increased saccadic distractibility in tardive dyskinesia: functional evidence for subcortical GABA dysfunction. Biol Psychiatry 1989; 25: 49–59.
  Article CAS PubMed Google Scholar
• Swerdlow NR, Braff DL, Taaid N, Geyer MA . Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 1994; 51: 139–154.
  Article CAS PubMed Google Scholar
• Swerdlow NR, Braff DL, Geyer MA . Cross-species studies of sensorimotor gating of the startle reflex. Ann N Y Acad Sci 1999; 877: 202–216.
  Article CAS PubMed Google Scholar
• Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M et al. Association of promotor variants in the alpha 7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch Gen Psychiatry 2002; 59: 1085–1096.
  Article CAS PubMed Google Scholar
• Merritt RD, Balogh DW . Critical stimulus duration: schizophrenic trait or state? Schizophr Bull 1985; 11: 341–343.
  Article CAS PubMed Google Scholar
• Braff DL . Impaired speed of information processing in nonmedicated schizotypal patients. Schizophr Bull 1981; 7: 499–508.
  Article CAS PubMed Google Scholar
• Green MF, Nuechterlein KH, Breitmeyer B . Backward masking performance in unaffected siblings of schizophrenic patients. Evidence for a vulnerability indicator. Arch Gen Psychiatry 1997; 54: 465–472.
  Article CAS PubMed Google Scholar
• Nuechterlein KH . Signal detection in vigilance tasks and behavioral attributes among offspring of schizophrenic mothers and among hyperactive children. J Abnorm Psychol 1983; 92: 4–28.
  Article CAS PubMed Google Scholar
• Park S, Holzman PS, Goldman-Rakic PS . Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry 1995; 52: 821–828.
  Article CAS PubMed Google Scholar
• Cannon TD, Mednick SA, Parnas J, Schulsinger F, Praestholm J, Vestergaard A . Developmental brain abnormalities in the offspring of schizophrenic mothers. II. Structural brain characteristics of schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 1994; 51: 955–962.
  Article CAS PubMed Google Scholar
• Faraone SV, Seidman LJ, Kremen WS, Pepple JR, Lyons MJ, Tsuang MT . Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficacy analysis. JAbnorm Psychol 1995; 104: 286–304.
  Article CAS Google Scholar
• Condray R, Steinhauer SR . Schizotypal personality disorder in individuals with and without schizophrenic relatives: similarities and contrasts in neurocognitive and clinical functioning. Schizophr Res 1992; 7: 33–41.
  Article CAS PubMed Google Scholar
• Condray R, Steinhauer SR, van Kammen DP, Kasparek A . Working memory capacity predicts language comprehension in schizophrenic patients. Schizophr Res 1996; 20: 1–13.
  Article CAS PubMed Google Scholar
• Keefe RS, Silverman JM, Mohs RC, Siever LJ, Harvey PD, Friedman L et al. Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Arch Gen Psychiatry 1997; 54: 169–176.
  Article CAS PubMed Google Scholar
• Pogue-Geile MF, Garrett AH, Brunke JJ, Hall JK . Neuropsychological impairments are increased in siblings of schizophrenic patients. Schiophr Res 1991; 4: 390.
  Article Google Scholar
• Roxborough H, Muir WJ, Blackwood DH, Walker MT, Blackburn IM . Neuropsychological and P300 abnormalities in schizophrenics and their relatives. Psychol Med 1993; 23: 305–314.
  Article CAS PubMed Google Scholar
• Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S et al. Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 2002; 71: 877–892.
  Article PubMed PubMed Central Google Scholar
• Schwab SG, Knapp M, Mondabon S, Hallmayer J, Borrmann-Hassenbach M, Albus M et al. Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families. Am J Hum Genet 2003; 72: 185–190.
  Article CAS PubMed Google Scholar
• Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H et al. Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. Proc Natl Acad Sci USA 2002; 99: 13675–13680, 10-15-2002.
  Article CAS PubMed PubMed Central Google Scholar
• Chowdari KV, Mirnics K, Semwal P, Wood J, Lawrence E, Bhatia T et al. Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet 2002; 11: 1373–1380.
  Article CAS PubMed Google Scholar
• Liu H, Heath SC, Sobin C, Roos JL, Galke BL, Blundell ML et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci USA 2002; 99: 3717–3722.
  Article CAS PubMed PubMed Central Google Scholar
• Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917–6922.
  Article CAS PubMed PubMed Central Google Scholar
• Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A et al. A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 2002; 71: 1296–1302.
  Article CAS PubMed PubMed Central Google Scholar
• Harrison PJ, Owen M . Genes for schizophrenia? Recent findings and their pathophysiological implications. Lancet 2003; 361: 417–419.
  Article CAS PubMed Google Scholar
• Shelton RC, Weinberger DR . Brain morphology in schizophrenia. In: Meltzer HY (ed). Psychopharmacology: The Third Generation of Progress. Raven Press: New York, NY, 1987 pp 773–781.
  Google Scholar
• Gur RE, Pearlson GD . Neuroimaging in schizophrenia research [Review]. Schizophr Bull 1993; 19: 337–353.
  Article CAS PubMed Google Scholar
• Shenton ME, Dickey CC, Frumin M, McCarley RW . A review of MRI findings in schizophrenia. Schizophr Res 2001; 49: 1–52.
  Article CAS PubMed PubMed Central Google Scholar
• Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L . Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 1976; 2: 924–926.
  Article CAS PubMed Google Scholar
• Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR . Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia [published erratum appears in N Engl J Med 1990 May 31;322(22):1616]. N Engl J Med 1990; 322: 789–794.
  Article CAS PubMed Google Scholar
• Barta PE, Pearlson GD, Powers RE, Richards SS, Tune LE . Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry 1990; 147: 1457–1462.
  Article CAS PubMed Google Scholar
• Bogerts B, Ashtari M, Degreef G, Alvir JM, Bilder RM, Lieberman JA . Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Res 1990; 35: 1–13.
  Article CAS PubMed Google Scholar
• Breier A, Buchanan RW, Elkashef A, Munson RC, Kirkpatrick B, Gellad F . Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. Arch Gen Psychiatry 1992; 49: 921–926.
  Article CAS PubMed Google Scholar
• Csernansky JG, Joshi S, Wang L, Haller JW, Gado M, Miller JP et al. Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proc Natl Acad Sci USA 1998; 95: 11406–11411.
  Article CAS PubMed PubMed Central Google Scholar
• Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG et al. Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. N Engl J Med 1992; 327: 604–612.
  Article CAS PubMed Google Scholar
• McCarley RW, Shenton ME, O'Donnell BF, Faux SF, Kikinis R, Nestor PG et al. Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. Arch Gen Psychiatry 1993; 50: 190–197.
  Article CAS PubMed Google Scholar
• Pearlson GD, Marsh L . Magnetic resonance imaging in psychiatry. In: Oldham JM, Riba MB, Tasman A (eds). American Psychiatric Press Review of Psychiatry, Vol. 12. American Psychiatric Press: Washington, DC, 1993, pp 347–381.
  Google Scholar
• Andreasen NC, Rezai K, Alliger RJ, Swayze VW, Flaum M, Kirchner P et al. Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Arch Gen Psychiatry 1992; 49: 943–958.
  Article CAS PubMed Google Scholar
• Ingvar DH, Franzen G . Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand 1974; 50: 425–462.
  Article CAS PubMed Google Scholar
• Buchsbaum MS, Ingvar DH, Kessler R, Waters RN, Cappelletti J, van Kammen DP et al. Cerebral glucography with positron tomography. Arch Gen Psychiatry 1982; 39: 251–259.
  Article CAS PubMed Google Scholar
• Buchsbaum MS, DeLisi LE, Holcomb HH, Cappelletti J, King AC, Johnson J et al. Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. Arch Gen Psychiatry 1984; 41: 1159–1166.
  Article CAS PubMed Google Scholar
• Tamminga CA, Thaker GK, Buchanan R, Kirkpatrick B, Alphs LD, Chase TN et al. Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 1992; 49: 522–530.
  Article CAS PubMed Google Scholar
• Cleghorn JM, Kaplan RD, Nahmias C, Garnett ES, Szechtman H, Szechtman B . Inferior parietal region implicated in neurocognitive impairment in schizophrenia [letter; comment]. Arch Gen Psychiatry 1989; 46: 758–760.
  Article CAS PubMed Google Scholar
• Holcomb HH, Cascella NG, Thaker GK, Medoff DR, Dannals RF, Tamminga CA . Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol. Am J Psychiatry 1996; 153: 41–49.
  Article CAS PubMed Google Scholar
• Spence SA, Brooks DJ, Hirsch SR, Liddle PF, Meehan J, Grasby PM . A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control). Brain 1997; 120(Part 11): 1997–2011.
  Article PubMed Google Scholar
• Heckers S, Rauch SL, Goff D, Savage CR, Schacter DLFAJ, Alpert NM . Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nature 1998; 1: 318–323.
  CAS Google Scholar
• Artiges E, Salame P, Recasens C, Poline JB, Attar-Levy D, De La RA et al. Working memory control in patients with schizophrenia: a PET study during a random number generation task. Am J Psychiatry 2000; 157: 1517–1519.
  Article CAS PubMed Google Scholar
• Heckers S, Goff D, Schacter DL, Savage CR, Fischman AJ, Alpert NM et al. Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia. Arch Gen Psychiatry 1999; 56: 1117–1123.
  Article CAS PubMed Google Scholar
• 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.
  Article CAS PubMed Google Scholar
• Harrison PJ, Eastwood SL . Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia. Hippocampus 2001; 11: 508–519.
  Article CAS PubMed Google Scholar
• Liddle PF, Friston KJ, Frith CD, Hirsch SR, Jones T, Frackowiak RS . Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry 1992; 160: 179–186.
  Article CAS PubMed Google Scholar
• Silbersweig DA, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S et al. A functional neuroanatomy of hallucinations in schizophrenia. Nature 1995; 378: 176–179.
  Article CAS PubMed Google Scholar
• Dolan RJ, Fletcher P, Frith CD, Friston KJ, Frackowiak RSJ, Grasby PM . Dopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia. Nature 1995; 378: 180–182.
  Article CAS PubMed Google Scholar
• Weinberger DR, Berman KF, Suddath R, Torrey EF . Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 1992; 149: 890–897.
  Article CAS PubMed Google Scholar
• Frith CD, Friston KJ, Herold S, Silbersweig D, Fletcher P, Cahill C et al. Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task. Br J Psychiatry 1995; 167: 343–349.
  Article CAS PubMed Google Scholar
• Spence SA, Liddle PF, Stefan MD, Hellewell JS, Sharma T, Friston KJ et al. Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised. Br J Psychiatry 2000; 176: 52–60.
  Article CAS PubMed Google Scholar
• Jennings JM, McIntosh AR, Kapur S, Zipursky RB, Houle S . Functional network differences in schizophrenia: a rCBF study of semantic processing. NeuroReport 1998; 9: 1697–1700.
  Article CAS PubMed Google Scholar
• Manoach DS, Press DZ, Thangaraj V, Searl MM, Goff DC, Halpern E et al. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry 1999; 45: 1128–1137.
  Article CAS PubMed Google Scholar
• Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E et al. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 2000; 48: 99–109.
  Article CAS PubMed Google Scholar
• Callicott JH, Ramsey NF, Tallent K, Bertolino A, Knable MB, Coppola R et al. Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia. Neuropsychopharmacology 1998; 18: 186–196.
  Article CAS PubMed Google Scholar
• Stevens AA, Goldman-Rakic PS, Gore JC, Fulbright RK, Wexler BE . Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging. Arch Gen Psychiatry 1998; 55: 1097–1103.
  Article CAS PubMed Google Scholar
• Callicott JH, Mattay VS, Bertolino A, Finn K, Coppola R, Frank JA et al. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex 1999; 9: 20–26.
  Article CAS PubMed Google Scholar
• Bogerts B . Recent advances in the neuropathology of schizophrenia [Review]. Schizophr Bull 1993; 19: 431–445.
  Article CAS PubMed Google Scholar
• Harrison PJ . The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999; 122: 593–624.
  Article PubMed Google Scholar
• Jeste DV, Lohr JB . Hippocampal pathologic findings in schizophrenia. A morphometric study. Arch Gen Psychiatry 1989; 46: 1019–1024.
  Article CAS PubMed Google Scholar
• Falkai P, Bogerts B . Cell loss in the hippocampus of schizophrenics. Eur Arch Psychiatry Neurol Sci 1986; 236: 154–161.
  Article CAS PubMed Google Scholar
• Suddath RL, Casanova MF, Goldberg TE, Daniel DG, Kelsoe Jr JR, Weinberger DR . Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. Am J Psychiatry 1989; 146: 464–472.
  Article CAS PubMed Google Scholar
• Scheibel AB, Kovelman JA . Disorientation of the hippocampal pyramidal cell and its processes in schizophrenic patients (letter). Biol Psychiatry 1981; 16: 101–102.
  Google Scholar
• Colter N, Battal S, Crow TJ, Johnstone EC, Brown R, Bruton C . White matter reduction in the parahippocampal gyrus of patients with schizophrenia [letter]. Arch Gen Psychiatry 1987; 44: 1023.
  Article CAS PubMed Google Scholar
• Arnold SE, Hyman BT, Van Hoesen GW, Damasio AR . Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry 1991; 48: 625–632.
  Article CAS PubMed Google Scholar
• Pakkenberg B . Post-mortem study of chronic schizophrenic brains. Br J Psychiatry 1987; 151: 744–752.
  Article CAS PubMed Google Scholar
• Rosenthal R, Bigelow LB . Quantitative brain measurements in chronic schizophrenia. Br J Psychiatry 1972; 121: 259–264.
  Article CAS PubMed Google Scholar
• Heckers S, Heinsen H, Heinsen Y, Beckmann H . Cortex, white matter, and basal ganglia in schizophrenia: a volumetric postmortem study. Biol Psychiatry 1991; 29: 556–566.
  Article CAS PubMed Google Scholar
• Selemon LD, Kleinman JE, Herman MM, Goldman-Rakic PS . Smaller frontal gray matter volume in postmortem schizophrenic brains. Am J Psychiatry 2002; 159: 1983–1991.
  Article PubMed Google Scholar
• Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney Jr WE et al. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 1995; 52: 258–266.
  Article CAS PubMed Google Scholar
• Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA . Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 2000; 57: 237–245.
  Article CAS PubMed Google Scholar
• Lewis DA . GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Brain Res Rev 2000; 31: 270–276.
  Article CAS PubMed Google Scholar
• Treff WM, Hempel KJ . Die Zelidichte bei Schizophrenen und linisch Gesunden. J Hirnforsch 1958; 4: 314–369.
  CAS PubMed Google Scholar
• Pakkenberg B . Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 1990; 47: 1023–1028.
  Article CAS PubMed Google Scholar
• Lesch A, Bogerts B . The diencephalon in schizophrenia: evidence for reduced thickness of the periventricular grey matter. Eur Arch Psychiatry Neurol Sci 1984; 234: 212–219.
  Article CAS PubMed Google Scholar
• Goldman-Rakic PS, Isseroff A, Schwartz ML, Bugbee NM . The neurobiology of cognitive development. In: Mussen P (ed). Handbook of Child Psychology: Biology and Infancy Development. John Wiley & Sons, Inc.: New York, NY, 1983 pp 281–344.
  Google Scholar
• Weinberger DR . Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44: 660–669.
  Article CAS PubMed Google Scholar
• Benes FM . Myelination of cortical-hippocampal relays during late adolescence. Schizophr Bull 1989; 15: 585–593.
  Article CAS PubMed Google Scholar
• Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP . Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics. J Neurosci 1992; 12: 924–929.
  Article CAS PubMed PubMed Central Google Scholar
• Akbarian S, Bunney Jr WE, Potkin SG, Wigal SB, Hagman JO, Sandman CA et al. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiatry 1993; 50: 169–177.
  Article CAS PubMed Google Scholar
• Jakob H, Beckmann H . Prenatal developmental disturbances in the limbic allocortex in schizophrenics. J Neural Transm 1986; 65: 303–326.
  Article CAS PubMed Google Scholar
• Altshuler LL, Conrad A, Kovelman JA, Scheibel A . Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev collection. Arch Gen Psychiatry 1987; 44: 1094–1098.
  Article CAS PubMed Google Scholar
• Elkashef AM, Issa F, Wyatt RJ . The biochemical basis of schizophrenia. In: Shriqui CL, Nasrallah HA (eds). Contemporary Issues in The Treatment of Schizophrenia. American Psychiatric Press: Washington, DC, 1995 pp 863.
  Google Scholar
• Davis KL, Kahn RS, Ko G, Davidson M . Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991; 148: 1474–1486.
  Article CAS PubMed Google Scholar
• Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R . Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 1999; 46: 56–72.
  Article CAS PubMed Google Scholar
• Wong DF, Wagner Jr HN, Tune LE, Dannals RF, Pearlson GD, Links JM et al. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics [published erratum appears in Science 1987 Feb 6;235(4789):623]. Science 1986; 234: 1558–1563.
  Article CAS PubMed Google Scholar
• Pearlson GD, Wong DF, Tune LE, Ross CA, Chase GA, Links JM et al. In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch Gen Psychiatry 1995; 52: 471–477.
  Article CAS PubMed Google Scholar
• Farde L, Wiesel FA, Stone-Elander S, Halldin C, Nordstrom AL, Hall H et al. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry 1990; 47: 213–219.
  Article CAS PubMed Google Scholar
• Hietala J, Syvälahti E, Vuorio K . Striatal Dopamine D2 Receptor Density in Neuroleptic-Naive Schizophrenics Studied with Positron Emission Tomography, in Biological Psychiatry. Excerpta Medica: Amsterdam, 1991.
  Google Scholar
• Martinot JL, Peron-Magnan P, Huret JD . Striatal D2 dopaminergic receptors assessed with positron emission tomography and [76Br]bromospiperone in untreated schizophrenic patients. Am J Psychiatry 1990; 147: 44–50.
  Article CAS PubMed Google Scholar
• Martinot JL, Paillere-Martinot ML, Loc'h C, Hardy P, Poirier MF, Mazoyer B et al. The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry 1991; 158: 346–350.
  Article CAS PubMed Google Scholar
• Hietala J, Syvälahti E, Vuorio K, Nagren K, Lehikoinen P, Ruotsalainen U et al. Striatal D2 dopamine receptor characteristics in neuroleptic- naive schizophrenic patients studied with positron emission tomography. Arch Gen Psychiatry 1994; 51: 116–123.
  Article CAS PubMed Google Scholar
• Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 1996; 93: 235–240.
  Article Google Scholar
• Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M et al. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 1998; 155: 761–767.
  Article CAS PubMed Google Scholar
• Castner SA, Goldman-Rakic PS . Enhancement of working memory in aged monkeys by a sensitizing regimen of dopamine D1 receptor stimulation. J Neurosci 2004; 24: 1446–1450.
  Article CAS PubMed PubMed Central Google Scholar
• Goldman-Rakic PS, Muly III EC, Williams GV . D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev 2000; 31: 295–301.
  Article CAS PubMed Google Scholar
• Karlsson P, Farde L, Halldin C, Sedvall G . PET study of D(1) dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am J Psychiatry 2002; 159: 761–767.
  Article PubMed Google Scholar
• Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y et al. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 2002; 22: 3708–3719.
  Article CAS PubMed PubMed Central Google Scholar
• Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR et al. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry 1999; 156: 1580–1589.
  Article CAS PubMed Google Scholar
• Akil M, Edgar CL, Pierri JN, Casali S, Lewis DA . Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects. Biol Psychiatry 2000; 47: 361–370.
  Article CAS PubMed Google Scholar
• Goldman-Rakic PS, Castner SA, Svensson TH, Siever LJ, Williams GV . Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology 2004; 174: 3–16.
  Article CAS PubMed Google Scholar
• Freedman DX . LSD, psychotogenic procedures, and brain neurohumors. Psychopharmacol Bull 1975; 11: 42–43.
  CAS PubMed Google Scholar
• Harrison PJ . Neurochemical alterations in schizophrenia affecting the putative receptor targets of atypical antipsychotics. Focus on dopamine (D1, D3, D4) and 5-HT2a receptors. Br J Psychiatry Suppl 1999; 38: 12–22.
  Article Google Scholar
• Marcus MM, Nomikos GG, Svensson TH . Effects of atypical antipsychotic drugs on dopamine output in the shell and core of the nucleus accumbens: role of 5-HT (2A) and alpha(1)-adrenoceptor antagonism. Eur Neuropsychopharmacol 2000; 10: 245–253.
  Article CAS PubMed Google Scholar
• Kuroki T, Meltzer HY, Ichikawa J . 5-HT 2A receptor stimulation by DOI, a 5-HT 2A/2C receptor agonist, potentiates amphetamine-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Brain Res 2003; 972: 216–221.
  Article CAS PubMed Google Scholar
• de Paulis T . M-100907 (Aventis). Curr Opin Investig Drugs 2001; 2: 123–132.
  CAS PubMed Google Scholar
• Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmuller B . Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 1980; 20: 379–382.
  Article CAS PubMed Google Scholar
• Macciardi F, Lucca A, Catalano M, Marino C, Zanardi R, Smeraldi E . Amino acid patterns in schizophrenia: some new findings. Psychiatry Res 1990; 32: 63–70.
  Article CAS PubMed Google Scholar
• Korpi ER, Kaufmann CA, Marnela KM, Weinberger DR . Cerebrospinal fluid amino acid concentrations in chronic schizophrenia. Psychiatry Res 1987; 20: 337–345.
  Article CAS PubMed Google Scholar
• Gattaz WF, Gasser T, Beckmann H . Multidimensional analysis of the concentrations of 17 substances in the CSF of schizophrenics and controls. Biol Psychiatry 1985; 20: 360–366.
  Article CAS PubMed Google Scholar
• Anis NA, Berry SC, Burton NR, Lodge D . The dissociative anesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by _N_- methyl-D-aspartate. Br J Pharmacol 1983; 79: 565–575.
  Article CAS PubMed PubMed Central Google Scholar
• Domino EF, Luby E . Abnormal mental states induced by phencyclidine as a model of schizophrenia. In: Domino EF (ed). PCP (Phencyclidine): Historical and Current Perspectives. NPP Books: Ann Arbor, MI, 1981.
  Google Scholar
• Deutsch SI, Mastropaolo J, Schwartz BL, Rosse RB, Morihisa JM . A ‘glutamatergic hypothesis’ of schizophrenia. Rationale for pharmacotherapy with glycine [Review]. Clin Neuropharmacol 1989; 12: 1–13.
  Article CAS PubMed Google Scholar
• Ulas J, Cotman CW . Excitatory amino acid receptors in schizophrenia [Review]. Schizophr Bull 1993; 19: 105–117.
  Article CAS PubMed Google Scholar
• Tamminga CA, Vogel M, Gao X, Lahti AC, Holcomb HH . The limbic cortex in schizophrenia: focus on the anterior cingulate. Brain Res Brain Res Rev 2000; 31: 364–370.
  Article CAS PubMed Google Scholar
• Holcomb HH, Lahti AC, Medoff DR, Weiler M, Dannals RF, Tamminga CA . Brain activation patterns in schizophrenic and comparison volunteers during a matched-performance auditory recognition task. Am J Psychiatry 2000; 157: 1634–1645.
  Article CAS PubMed Google Scholar
• Medoff DR, Holcomb HH, Lahti AC, Tamminga CA . Probing the human hippocampus using rCBF: contrasts in schizophrenia. Hippocampus 2001; 11: 543–550.
  Article CAS PubMed Google Scholar
• Goldman-Rakic PS . Psychopathology and neuropathology of prefrontal cortex in schizophrenia. In: Fog R, Gerlach J, Hemmingsen R (eds). Schizophrenia: an Integrated View. Munksgaard: Copenhagen, Denmark, 1995 pp 126–138.
  Google Scholar