Skip to main content
Log in

Recent advances in treating cognitive impairment in schizophrenia

  • Review
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Introduction

Schizophrenia is often associated with chronic disability and poor outcome. In addition to positive symptoms, such as hallucinations and delusions, and negative symptoms including poverty of speech and blunted affect, schizophrenia is also associated with deficits in cognitive function. It has been increasingly recognized that the severity of cognitive impairment is a major determinant of outcome. Therefore, interventions to improve cognitive function also have the capacity to improve quality of life and social and occupational outcomes. Whilst some of the antipsychotic drugs have shown some selective benefits, there is some controversy about the extent of these benefits.

Objectives

This article provides an overview of research into drugs that might enhance cognition in schizophrenia.

Conclusion

Drugs such as modafanil and galantamine are being evaluated, and a number of new drugs are currently in development. Standardized cognitive assessment measures are being developed so studies can be compared more easily. This field is advancing rapidly, but as yet, no widely applicable, evidence-based treatments are available to the clinician.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adler LE, Hoffer LD, Wiser A, Freedman R (1993) Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 150:1856–1861

    PubMed  CAS  Google Scholar 

  • Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR, Lewis DA (1999) Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry 156:1580–1589

    PubMed  CAS  Google Scholar 

  • Akil M, Kolachana BS, Rothmond DA, Hyde TM, Weinberger DR, Kleinman JE (2003) Catechol-O-Methyltransferase genotype and dopamine regulation in the human brain. J Neurosci 23:2008–2013

    PubMed  CAS  Google Scholar 

  • Alves F, Figee M, van Amelsvoort T, Veltman D, de Haan L (2008) The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication. Psychopharmacol Bull 41:121–132

    Google Scholar 

  • Ballon JS, Feifel D (2006) A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry 67:554–566

    Article  PubMed  CAS  Google Scholar 

  • Barch DM, Carter CS (2005) Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res 77:43–58

    Article  PubMed  Google Scholar 

  • Barch DM, Carter CS, the CNTRICS Executive Committee (2008) Measurement issues in the use of cognitive neuroscience tasks in drug development for impaired cognition in schizophrenia: a report of the second consensus building conference of the CNTRICS initiative. Schizophr Bull 34:613–618

    Article  PubMed  Google Scholar 

  • Bardgett ME, Points M, Ramsey-Faulkner C, Topmiller J, Roflow J, McDaniel T, Lamontagne T, Griffith MS (2008) The effects of clonidine on discrete-trial delayed spatial alternation in two rat models of memory loss. Neuropsychopharmacology 33:1980–1991

    Article  PubMed  CAS  Google Scholar 

  • Barnett JH, Scoriels L, Munafò MR (2008) Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene Val158/108Met polymorphism. Biol Psychiatry 64:137–144

    Article  PubMed  CAS  Google Scholar 

  • Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP, Deckersbach T, Kelly JF, Freudenreich O, Goff DC, Evins AE (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33:480–490

    Article  PubMed  CAS  Google Scholar 

  • Bilder RM, Goldman RS, Robinson D, Reiter G, Bell L, Bates J, Pappadopulos E, Willson DF, Alvir JM, Woerner MG, Geisler S, Kane JM, Lieberman JA (2000) Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry 157:549–559

    Article  PubMed  CAS  Google Scholar 

  • Birks J (2006) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 1:CD005593

    PubMed  Google Scholar 

  • Boast C, Bartolomeo AC, Morris H, Moyer JA (1999) 5HT antagonists attenuate MK801-impaired radial arm maze performance in rats. Neurobiol Learn Mem 71:259–271

    Article  PubMed  CAS  Google Scholar 

  • Bodick NC, Offen WW, Levey AI, Cutler NR, Gauthier SG, Satlin A, Shannon HE, Tollefson GD, Rasmussen K, Bymaster FP, Hurley DJ, Potter WZ, Paul SM (1997) Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol 54:465–473

    PubMed  CAS  Google Scholar 

  • Bora E, Veznedaroglu B, Kayahan B (2005) The effect of galantamine added to clozapine on cognition of five patients with schizophrenia. Clin Neuropharmacol 28:139–141

    Article  PubMed  Google Scholar 

  • Breese CR, Lee MJ, Adams CE, Sullivan B, Logel J, Gillen KM, Marks MJ, Collins AC, Leonard S (2000) Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology 23:351–364

    Article  PubMed  CAS  Google Scholar 

  • Briggs CA, Anderson DJ, Brioni JD, Buccafusco JJ, Buckley MJ, Campbell JE, Decker MW, Donnelly-Roberts D, Elliot RL, Gopalakrishnan M, Holladay MW, Hui Y-H, Jackson WJ, Kim DJB, Marsh KC, O’Neill A, Prendergast MA, Ryther KB, Sullivan JP, Arneric SP (1996) Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo. Pharmacol Biochem Behav 57:231–241

    Article  Google Scholar 

  • Brockhaus-Dumke A, Schultze-Lutter F, Mueller R, Tendolkar I, Bechdolf A, Pukrop R, Klosterkoetter J, Ruhrmann S (2008) Sensory gating in schizophrenia: P50 and N100 gating in antipsychotic-free subjects at risk, first-episode, and chronic patients. Biol Psychiatry 64(5):376–384

    Article  PubMed  Google Scholar 

  • Browman KE, Curzon P, Pan JB, Molesky AL, Komater VA, Decker MW, Brioni JD, Moreland RB, Fox GB (2005) A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats. Pharmacol Biochem Behav 82:148–155

    Article  PubMed  CAS  Google Scholar 

  • Buchanan RW, Freedman R, Javitt DC, Abi-Dargham A, Lieberman JA (2007a) Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull 33:1120–1130

    Article  PubMed  Google Scholar 

  • Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, Heresco-Levy U, Carpenter WT (2007b) The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry 164:1593–1602

    Article  PubMed  Google Scholar 

  • Buchanan RW, Conley RR, Dickinson D, Ball MP, Feldman S, Gold JM, McMahon RP (2008) Galantamine for the treatment of cognitive impairments in people with schizophrenia. Am J Psychiatry 165:82–89

    Article  PubMed  Google Scholar 

  • Bymaster FP, Felder C, Ahmed S, McKinzie D (2002) Muscarinic receptors as a target for drugs treating schizophrenia. Curr Drug Targets CNS Neurol Disord 1:163–181

    Article  PubMed  CAS  Google Scholar 

  • Carlsson A (1977) Does dopamine play a role in schizophrenia? Psychol Med 7:583–597

    PubMed  CAS  Google Scholar 

  • Carter CS (2005) Applying new approaches from cognitive neuroscience to enhance drug development for the treatment of impaired cognition in schizophrenia. Schizophr Bull 31:810–815

    Article  PubMed  Google Scholar 

  • Carter CS, Barch DM, Buchanan RW, Bullmore E, Krystal JH, Cohen J, Geyer M, Green M, Nuechterlein KH, Robbins T, Silverstein S, Smith EE, Strauss M, Wykes T, Heinssen R (2008) Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biol Psychiatry 64:4–10

    Article  PubMed  Google Scholar 

  • Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005) Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry 57:1117–1127

    Article  PubMed  CAS  Google Scholar 

  • Cassens G, Inglis AK, Appelbaum PS, Gutheil TG (1990) Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull 16:477–499

    PubMed  CAS  Google Scholar 

  • Castner SA, Williams GV, Goldman-Rakic PS (2000) Reversal of antipsychotic-induced working memory deficits by short term dopamine D1 receptor stimulation. Science 287:2020–2022

    Article  PubMed  CAS  Google Scholar 

  • Censits DM, Ragland JD, Gur RC, Gur RE (1997) Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study. Schizophr Res 24:289–298

    Article  PubMed  CAS  Google Scholar 

  • Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Kirshner MA, Bies RR, Kapur S, Gharabawi G (2006) A model of anticholinergic activity of atypical antipsychotic medications. Schizophr Res 88:63–72

    Article  PubMed  Google Scholar 

  • Chouinard S, Stip E, Poulin J, Melun JP, Godbout R, Guillem F, Cohen H (2007) Rivastigmine treatment as an add-on to antipsychotics in patients with schizophrenia and cognitive deficits. Curr Med Res Opin 23:575–583

    Article  PubMed  CAS  Google Scholar 

  • Corrigan MH, Gallen CC, Bonura ML, Merchant KM (2004) Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial. Biol Psychiatry 55:445–451

    Article  PubMed  CAS  Google Scholar 

  • Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483

    Article  PubMed  CAS  Google Scholar 

  • David AS, Malmberg A, Brandt L, Allebeck P, Lewis G (1997) IQ and risk for schizophrenia: a population-based cohort study. Psychol Med 27:1311–1323

    Article  PubMed  CAS  Google Scholar 

  • Davies MA, Compton-Toth BA, Hufeisen SJ, Meltzer HY, Roth BL (2004) The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine’s actions? Psychopharmacology (Berl) 178:451–460

    Article  CAS  Google Scholar 

  • Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E (2002) Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry 7:1083–1091

    Article  PubMed  CAS  Google Scholar 

  • de Fiebre CM, Meyer EM, Henry JC, Muraskin SI, Kem WR, Papke RL (1995) Characterization of a series of anabaseine derived compounds reveals that the 3-(4)-dimethylaminocinnamylidine derivative is a selective agonist at neuronal nicotinic alpha7/125 i-alpha-bungarotoxin receptor subtypes. Mol Pharmacol 47:164–171

    PubMed  Google Scholar 

  • de Haas SL, de Visser SJ, van der Post JP, de Smet M, Schoemaker RC, Rijnbeek B, Cohen AF, Vega JM, Agrawal NGB, Goel TV, Simpson RC, Pearson LK, Li S, Hesney M, Murphy MG, Van Gerven JMA (2006) Pharmacodynamic and pharmacokinetic effects of TPA023, a GABAA a2,3 subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers. J Psychopharmacol 21:374–383

    Article  PubMed  Google Scholar 

  • deLeon J, Diaz FJ (2005) A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res 76:135–157

    Article  Google Scholar 

  • De Luca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL (2004) Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients. Neuropsychopharmacology 29:1522–1526

    Article  PubMed  CAS  Google Scholar 

  • Dickerson F, Boronow JJ, Ringel N, Parente F (1999) Social functioning and neurocognitive deficits in outpatients with schizophrenia: a 2-year follow-up. Schizophr Res 37:13–20

    Article  PubMed  CAS  Google Scholar 

  • Done DJ, Crow TJ, Johnstone EC, Sacker A (1994) Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11. Br Med J 309:699–703

    CAS  Google Scholar 

  • Dutta R, Greene T, Addington J, McKenzie K, Phillips M, Murray RM (2007) Biological, life course, and cross-cultural studies all point toward the value of dimensional and developmental ratings in the classification of psychosis. Schizophr Bull 33:868–876

    Article  PubMed  Google Scholar 

  • Dyer MA, Freudenreich O, Culhane MA, Pachas GN, Deckersbach T, Murphy E, Goff DC, Evins AE (2008) High-dose galantamine augmentation inferior to placebo on attention, inhibitory control and working memory performance in nonsmokers with schizophrenia. Schizophr Res 102(1–3):88–95

    Article  PubMed  Google Scholar 

  • Field CD, Galletly CA, Anderson D, Walker P (1997) Computer-aided cognitive rehabilitation: possible application to the attentional deficit of schizophrenia. A report of negative results. Percept Mot Skills 85:995–1002

    CAS  Google Scholar 

  • Fields RB, Van Kammen DP, Peters JL, Rosen J, Van Kammen WB, Nugent A, Stipetic M, Linnoila M (1988) Clonidine improves memory function in schizophrenia independently from change in psychosis. Preliminary findings. Schizophr Res 1:417–423

    Article  PubMed  CAS  Google Scholar 

  • Frangou S, Hadjulis M, Vourdas A (2008) The Maudsley Early Onset Schizophrenia Study: cognitive function over a 4-year follow-up period. Schizophr Bull 34:52–59

    Article  PubMed  Google Scholar 

  • Fredrickson A, Snyder PJ, Cromer J, Thomas E, Lewis M, Maruff P (2008) The use of effect sizes to characterize the nature of cognitive change in psychopharmacological studies: an example with scopolamine. Hum Psychopharmacol 23(5):425–436

    Article  PubMed  CAS  Google Scholar 

  • Freedman R, Hall M, Adler LE, Leonard S (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 38:22–33

    Article  PubMed  CAS  Google Scholar 

  • Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams CE, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 94:587–592

    Article  PubMed  CAS  Google Scholar 

  • Freedman R, Leonard S, Waldo M, Gault J, Olincy A, Adler LE (2006) Characterization of allelic variants at chromosome 15q14 in schizophrenia. Genes Brain Behav 5 Suppl 1:14–22

    Article  CAS  Google Scholar 

  • Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR (2008) Initial phase 2 trial of a nicotinic agonist in schizophrenia. Am J Psychiatry 165:1040–1047

    Article  PubMed  Google Scholar 

  • Friedman JI (2004) Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonists. Psychopharmacology 174:45–53

    Article  PubMed  CAS  Google Scholar 

  • Friedman JI, Adler DN, Temporini HD, Kemether E, Harvey PD, White L, Parrella M, Davis KL (2001) Guanfacine treatment of cognitive impairment in schizophrenia. Neuropsychopharmacology 25:402–409

    Article  PubMed  CAS  Google Scholar 

  • Friedman JI, Adler DN, Howanitz E, Harvey PD, Brenner G, Temporini H, White L, Parrella M, Davis KL (2002) A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia. Biol. Psychiatry 51:349–357

    Article  PubMed  CAS  Google Scholar 

  • Furey ML, Pietrini P, Haxby JV (2000) Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science 290:2315–2319

    Article  PubMed  CAS  Google Scholar 

  • Galletly CA, Clark CR, McFarlane AC (2000) Treating cognitive dysfunction in patients with schizophrenia. J Psychiatry Neurosci 25:117–124

    PubMed  CAS  Google Scholar 

  • Galletly CA, Clark CR, McFarlane AC (2005) Clozapine improves working memory updating in schizophrenia. Eur Neuropsychopharmacol 15:601–608

    Article  PubMed  CAS  Google Scholar 

  • Galletly CA, McFarlane AC, Clark CR (2007) Impaired updating of working memory in schizophrenia. Int J Psychophysiol 63:265–274

    Article  PubMed  Google Scholar 

  • Gasparini M, Fabrizio E, Bonifati V, Meco G (1997) Cognitive improvement during Tolcapone treatment in Parkinson’s disease. J Neural Transm 104:887–894

    Article  PubMed  CAS  Google Scholar 

  • George MS, Molnar CE, Grenesko EL, Anderson B, Mu Q, Johnson K, Nahas Z, Knable M, Fernandes P, Juncos J, Huang X, Nichols DE, Mailman RB (2007) A single 20mg dose of dihydrexidine (DAR-0100), a full dopamine D (1) agonist, is safe and tolerated in patients with schizophrenia. Schizophr Res 93:42–50

    Article  PubMed  Google Scholar 

  • Goff DC, Leahy L, Berman I, Posever T, Herz L, Leon AC, Johnson SA, Lynch G (2001) A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol 21:484–487

    Article  PubMed  CAS  Google Scholar 

  • Goff DC, Keefe R, Citrome L, Davy K, Krystal JH, Large C, Thompson TR, Volavka J, Webster EL (2007) Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials. J Clin Psychopharmacol 27:582–589

    Article  PubMed  CAS  Google Scholar 

  • Goff DC, Lamberti JS, Leon AC, Green MF, Miller AL, Patel J, Manschreck T, Freudenreich O, Johnson SA (2008) A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia. Neuropsychopharmacology 33:465–472

    Article  PubMed  CAS  Google Scholar 

  • Goldberg TE, Egan MF, Gscheidle T, Coppola R, Weickert T, Kolachana BS, Goldman D, Weinberger DR (2003) Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 60:889–896

    Article  PubMed  CAS  Google Scholar 

  • Goldberg TE, Goldman RS, Burdick KE, Malhotra AK, Lencz T, Patel RC, Woerner MG, Schooler NR, Kane JM, Robinson DG (2007) Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Arch Gen Psychiatry 64:1115–1122

    Article  PubMed  CAS  Google Scholar 

  • Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330

    PubMed  CAS  Google Scholar 

  • Green MF (2007) Cognition, drug treatment, and functional outcome in schizophrenia: a tale of two transitions. Am J Psychiatry 164:992–994

    Article  PubMed  Google Scholar 

  • Green MF, Marshall BD Jr, Wirshing WC, Ames D, Marder SR, McGurk S, Kern RS, Mintz J (1997) Does risperidone improve verbal working memory in treatment-resistant schizophrenia? Am J Psychiatry 154:799–804

    PubMed  CAS  Google Scholar 

  • Green MF, Kern RS, Braff DL, Mintz J (2000) Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff? Schizophr Bull 26:119–136

    PubMed  CAS  Google Scholar 

  • Green MF, Nuechterlein KH, Kern RS, Baade LE, Fenton WS, Gold JM, Keefe RS, Mesholam-Gately R, Seidman LJ, Stover E, Marder SR (2008) Functional co-primary measures for clinical trials in schizophrenia: results from the MATRICS psychometric and standardization study. Am J Psychiatry 165:221–228

    Article  PubMed  Google Scholar 

  • Griffith JM, O’Neill J, Petty F, Garver D, Young D, Freedman R (1998) Nicotinic receptor desensitization and sensory gating deficits in schizophrenia. Biol Psychiatry 44:98–106

    Article  PubMed  CAS  Google Scholar 

  • Hampson RE, Rogers G, Lynch G, Deadwyler SA (1998) Facilitative effects of the ampakine CX516 on short-term memory in rats: enhancement of delayed-nonmatch-to-sample performance. J Neurosci 18:2740–2747

    PubMed  CAS  Google Scholar 

  • Harrison PJ (2008) Metabotropic glutamate receptor agonists for schizophrenia. Br J Psychiatry 192:86–87

    Article  PubMed  Google Scholar 

  • Harvey PD, Cornblatt B (2008) Pharmacological treatment of cognition in schizophrenia: an idea whose method has come. Am J Psychiatry 165:163–165

    Article  PubMed  Google Scholar 

  • Harvey PD, Bowie CR, Friedman JI (2001) Cognition in schizophrenia. Curr Psychiatry Rep 3:423–428

    Article  PubMed  CAS  Google Scholar 

  • Harvey PD, Rabinowitz J, Eerdekens M, Davidson M (2005) Treatment of cognitive impairment in early psychosis: a comparison of risperidone and haloperidol in a large long-term trial. Am J Psychiatry 162:1888–1895

    Article  PubMed  Google Scholar 

  • Hogarty GE, Flesher S, Ulrich R, Carter M, Greenwald D, Pogue-Geile M, Kechavan M, Cooley S, DiBarry AL, Garrett A, Parepally H, Zoretich R (2004) Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry 61:866–876

    Article  PubMed  Google Scholar 

  • Holthausen EA, Wiersma D, Cahn W, Kahn RS Dingemans PM, Schene AH, Van Den Bosch R (2007) Predictive value of cognition for different domains of outcome in recent-onset schizophrenia. Psychiatry Res 149:71–80

    Article  PubMed  Google Scholar 

  • Hunter MD, Ganesan V, Wilkinson ID, Spence SA (2006) Impact of modafinil on prefrontal executive function in schizophrenia. Am J Psychiatry 163:2184–2186

    Article  PubMed  Google Scholar 

  • Ichikawa J, Dai J, O’Laughlin IA, Fowler WL, Meltzer HY (2002) Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology 26:325–339

    Article  PubMed  CAS  Google Scholar 

  • Javitt DC (2008) Glycine Transport Inhibitors and the Treatment of Schizophrenia. Biol Psychiatry 63:6–8

    Article  PubMed  CAS  Google Scholar 

  • Javitt DC, Duncan L, Balla A, Sershen H (2005) Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action. Mol Psychiatry 10:275–287

    Article  PubMed  CAS  Google Scholar 

  • Jones P, Rodgers B, Murray R, Marmot M (1994) Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344:1398–1402

    Article  PubMed  CAS  Google Scholar 

  • Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, López-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rössler A, Grobbee DE, EUFEST study group (2008) Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371:1085–1097

    Article  PubMed  CAS  Google Scholar 

  • Keedy SK, Ebens CL, Keshavan MS, Sweeney JA (2006) Functional magnetic resonance imaging studies of eye movements in first episode schizophrenia: smooth pursuit, visually guided saccades and the oculomotor delayed response task. Psychiatry Res 146:199–211

    Article  PubMed  Google Scholar 

  • Keefe RS, Fenton WS (2007) How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull 33:912–920

    Article  PubMed  Google Scholar 

  • Keefe RS, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222

    PubMed  CAS  Google Scholar 

  • Keefe RS, Poe M, Walker TM, Kang JW, Harvey PD (2006) The Schizophrenia Cognition Rating Scale: an interview-based assessment and its relationship to cognition, real-world functioning, and functional capacity. Am J Psychiatry 163:426–432

    Article  PubMed  Google Scholar 

  • Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA, CATIE Investigators; Neurocognitive Working Group (2007a) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry 64:633–647

    Article  CAS  Google Scholar 

  • Keefe RS, Sweeney JA, Gu H, Hamer RM, Perkins DO, McEvoy JP, Lieberman JA (2007b) Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry 164:1061–1071

    Article  PubMed  Google Scholar 

  • Keefe RS, Malhotra AK, Meltzer HY, Kane JM, Buchanan RW, Murthy A, Sovel M, Li C, Goldman R (2008) Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial. Neuropsychopharmacology 33:1217–1228

    Article  PubMed  CAS  Google Scholar 

  • Kelly C, McCreadie RG (1999) Smoking habits, current symptoms, and premorbid characteristics of schizophrenic patients in Nithsdale, Scotland. Am J Psychiatry 156:1751–1757

    PubMed  CAS  Google Scholar 

  • Kelly RE Jr, Cohen LJ, Semple RJ, Bialer P, Lau A, Bodenheimer A, Neustadter E, Barenboim A, Galynker II (2006) Relationship between drug company funding and outcomes of clinical psychiatric research. Psychol Med 36:1647–1656

    Article  PubMed  Google Scholar 

  • Kern RS, Nuechterlein KH, Green MF, Baade LE, Fenton WS, Gold JM Keefe RSE, Mesholam-Gately R, Mintz J, Seidman LJ, Stover E, Marder SR (2008) The MATRICS consensus cognitive battery, part 2: co-norming and standardization. Am J Psychiatry 165:214–220

    Article  PubMed  Google Scholar 

  • Kramer MS, Last B, Getson A, Reines SA (1997) The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. D4 Dopamine Antagonist Group. Arch Gen Psychiatry 54:567–572

    CAS  Google Scholar 

  • Kraus MS, Keefe RS (2007) Cognition as an outcome measure in schizophrenia. Br J Psychiatry 191(Suppl. 50):s46–s51

    Article  Google Scholar 

  • Lee SW, Lee JG, Lee BJ, Kim YH (2007) A 12-week, double-blind, placebo-controlled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Int Clin Psychopharmacol 22:63–68

    Article  PubMed  CAS  Google Scholar 

  • Lieberman JA, Sheitman BB, Kinon BJ (1997) Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology 17:205–229

    Article  PubMed  CAS  Google Scholar 

  • Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1023

    Article  PubMed  CAS  Google Scholar 

  • Liljequist R, Haapalinna A, Ahlander M, Li YH, Mannisto PT (1997) Catechol O-methyltransferase inhibitor tolcapone has minor influence on performance in experimental memory models in rats. Behav Brain Res 82:195–202

    Article  PubMed  CAS  Google Scholar 

  • Litman RE, Su TP, Potter WZ, Hong WW, Pickar D (1996) Idazoxan and response to typical neuroleptics in treatment resistant schizophrenia. Comparison with the atypical neuroleptic, clozapine. Br J Psychiatry 168:571–579

    Article  PubMed  CAS  Google Scholar 

  • Maccabe JH (2008) Population-based cohort studies on premorbid cognitive function in schizophrenia. Epidemiol Rev (in press)

  • Manschreck TC, Boshes RA (2007) The CATIE schizophrenia trial: results, impact, controversy. Harv Rev Psychiatry 15:245–258

    Article  PubMed  Google Scholar 

  • Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci U S A 100:6186–6191

    Article  PubMed  CAS  Google Scholar 

  • McEvoy JP, Freudenreich O, Wilson W (1999) Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry 46:125–129

    Article  PubMed  CAS  Google Scholar 

  • McGurk SR, Meltzer HY (2000) The role of cognition in vocational functioning in schizophrenia. Schizophr Res 45:175–184

    Article  PubMed  CAS  Google Scholar 

  • McGurk SR, Mueser KT, Walling D, Harvey PD, Meltzer HY (2004) Cognitive functioning predicts outpatient service utilization in schizophrenia. Ment Health Serv Res 6:185–188

    Article  PubMed  Google Scholar 

  • McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT (2007) A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry 164:1791–1802

    Article  PubMed  Google Scholar 

  • Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Retrieved December 27, 2007 from http://www.matrics.ucla.edu/

  • Medalia A, Gold J, Merriam A (1988) The effects of neuroleptics on neuropsychological test results in schizophrenia. Arch Clin Neuropsychol 3:249–271

    PubMed  CAS  Google Scholar 

  • Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull, 25:233–255

    CAS  Google Scholar 

  • Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: a review. Schizophr Bull 2:19–76

    PubMed  CAS  Google Scholar 

  • Menniti FS, Chappie TA, Humphrey JM, Schmidt CJ (2007) Phosphodiesterase 10A inhibitors: a novel approach to the treatment of the symptoms of schizophrenia. Curr Opin Investig Drugs 8:54–59

    PubMed  CAS  Google Scholar 

  • Meyer EM, Tay ET, Papke RL, Meyers C, Huang GL, de Fiebre CM (1997) 3-2,4-Dimethoxybenzylidene-anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memoryrelated behaviors in a mecamylamine-sensitive manner. Brain Res 768:49–56

    Article  PubMed  CAS  Google Scholar 

  • Milev P, Ho BC, Arndt S, Andreasen NC (2005) Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry 162:495–506

    Article  PubMed  Google Scholar 

  • Mishara AL, Goldberg TE (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

    Article  PubMed  CAS  Google Scholar 

  • Morein-Zamir S, Turner DC, Sahakian BJ (2007) A review of the effects of modafinil on cognition in schizophrenia. Schizophr Bull 33:1298–1306

    Article  PubMed  Google Scholar 

  • Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51:173–184

    Article  PubMed  CAS  Google Scholar 

  • Mueser KT, McGurk SR (2004) Schizophrenia. Lancet 363:2063–2072

    Article  PubMed  Google Scholar 

  • Nagamoto HT, Adler LE, McRae KA, Huettl P, Cawthra E, Gerhardt G, Hea R, Griffith J (1999) Auditory P50 in schizophrenics on clozapine: improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol. Neuropsychobiology 39:10–17

    Article  PubMed  CAS  Google Scholar 

  • Noren U, Bjorner A, Sonesson O, Eriksson L (2006) Galantamine added to antipsychotic treatment in chronic schizophrenia: cognitive improvement? Schizophr Res 85:302–304

    Article  PubMed  CAS  Google Scholar 

  • Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK (2004) Identification of separable cognitive factors in schizophrenia. Schizophr Res 72:29–39

    Article  PubMed  Google Scholar 

  • Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR (2008) The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry 165:203–213

    Article  PubMed  Google Scholar 

  • Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leornard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R (2006) Proof-of-Concept Trial of an alpha7 Nicotinic Agonist in Schizophrenia. Arch Gen Psychiatry 63:630–638

    Article  PubMed  CAS  Google Scholar 

  • Owen MJ, Williams NM, O’Donovan MC (2004) The molecular genetics of schizophrenia: new findings promise new insights. Mol Psychiatry 9:14–27

    Article  PubMed  CAS  Google Scholar 

  • Palmer BA, Heaton RK, Glaksjo JA, Evans JD, Patterson TL, Golshan S, Jeste DV (2002) Heterogeneity in functional status among older outpatients with schizophrenia: employment history, living situation, and driving. Schizophr Res 55:205–215

    Article  PubMed  Google Scholar 

  • Perl O, Strous RD, Dranikov A, Chen R, Fuchs S (2006) Low levels of alpha7-nicotinic acetylcholine receptor mRNA on peripheral blood lymphocytes in schizophrenia and its association with illness severity. Neuropsychobiology 53:88–93

    Article  PubMed  CAS  Google Scholar 

  • Perlis RH, Perlis CS, Wu Y, Hwang C, Joseph M, Nierenberg AA (2005) Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Am J Psychiatry 162:1957–1960

    Article  PubMed  Google Scholar 

  • Perry KW, Nisenbaum LK, George CA, Shannon HE, Felder CC, Bymaster FP (2001) The muscarinic agonist xanomeline increases monoamine release and immediate early gene expression in the rat prefrontal cortex. Biol Psychiatry 49:716–725

    Article  PubMed  CAS  Google Scholar 

  • Porrino LJ, Daunais JB, Rogers GA, Hampson RE, Deadwyler SA (2005) Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates. PLoS Biol 3:e299

    Article  PubMed  CAS  Google Scholar 

  • Poyurovsky M, Koren D, Gonopolsky I, Schneidman M, Fuchs C, Weizman A, Weizman R (2003) Effect of the 5-HT2 antagonist mianserin on cognitive dysfunction in chronic schizophrenia patients: an add-on, double-blind placebo-controlled study. Eur Neuropsychopharmacol 13:123–128

    Article  PubMed  CAS  Google Scholar 

  • Praharaj SK, Verma P, Roy D, Singh A (2005) Is clonidine useful for treatment of clozapine-induced sialorrhea? J Psychopharmacol 19:426–428

    Article  PubMed  CAS  Google Scholar 

  • Pratt JA, Winchester C, Egerton A, Cochran SM, Morris BJ (2008) Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. Br J Pharmacol 153: Suppl 1:S465–S470

    Article  CAS  Google Scholar 

  • Puig O, Penadés R, Gastó C, Catalán R, Torres A, Salamero M (2008) Verbal memory, negative symptomatology and prediction of psychosocial functioning in schizophrenia. Psychiatry Res. 2008 158:11–17

    Article  Google Scholar 

  • Purdon SE, Malla A, Labelle A, Lit W (2001) Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. J Psychiatry Neurosci 26:137–149

    PubMed  CAS  Google Scholar 

  • Raedler TJ, Knable MB, Jones DW, Urbina RA, Gorey JG, Lee KS, Egan MF, Coppola R, Weinberger DR (2003) In vivo determination of muscarinic acetylcholine receptor availability in schizophrenia. Am J Psychiatry 160:118–127

    Article  PubMed  Google Scholar 

  • Raedler TJ, Bymaster FP, Tandon R, Copolov D, Dean B (2007) Towards a muscarinic hypothesis of schizophrenia. Mol Psychiatry 12:232–246

    PubMed  CAS  Google Scholar 

  • Ragland JD, Yoon J, Minzenberg MJ, Carter CS (2007) Neuroimaging of cognitive disability in schizophrenia: search for a pathophysiological mechanism. Int Rev Psychiatry 19:417–427

    Article  PubMed  CAS  Google Scholar 

  • Roth BL, Hanizavareh SM, Blum AE (2004) Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacology (Berl) 174:17–24

    Article  CAS  Google Scholar 

  • Sacco KA, Termine A, Seyal A, Dudas MM, Vessicchio JC, Krishnan-Sarin S, Jatlow PI, Wexler BE, George TP (2005) Effects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry 62:649–659

    Article  PubMed  Google Scholar 

  • Saykin AJ, Shtasel DL, Gur RE, Kester DB, Mozley LH, Stafiniak P, Gur RC (1994) Neuropsychological deficits in neuroleptic naive patients with first-episode Schizophrenia. Arch Gen Psychiatry 51:124–131

    PubMed  CAS  Google Scholar 

  • Scarr E, Cowie TF, Kanellakis S, Sundram S, Pantelis C, Dean B (2008) Decreased cortical muscarinic receptors define a subgroup of subjects with schizophrenia. Mol Psychiatry (in press)

  • Schubert MH, Young KA, Hicks PB (2006) Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry 60:530–533

    Article  PubMed  CAS  Google Scholar 

  • Sergi MJ, Rassovsky Y, Nuechterlein KH, Green MF (2006) Social perception as a mediator of the influence of early visual processing on functional status in schizophrenia. Am J Psychiatry 163:448–454

    Article  PubMed  Google Scholar 

  • Severance EG, Yolken RH (2008) Novel alpha7 nicotinic receptor isoforms and deficient cholinergic transcription in schizophrenia. Genes Brain Behav 7:37–45

    PubMed  CAS  Google Scholar 

  • Shannon HE, Rasmussen K, Bymaster FP, Hart JC, Peters SC, Swedberg MD, Jeppesen L, Sheardown MJ, Sauerberg P, Fink-Jensen A (2000) Xanomeline, an M(1)/M(4) preferring muscarinic cholinergic receptor agonist, produces antipsychotic-like activity in rats and mice. Schizophr Res 42:249–259

    Article  PubMed  CAS  Google Scholar 

  • Silverstein S, Schenkel LS, Valone C, Nuernberger SW (1998) Cognitive deficits and psychiatric rehabilitation outcomes in schizophrenia. Psychiatr Quart 69:169–191

    Article  CAS  Google Scholar 

  • Simosky JK, Stevens KE, Adler LE, Freedman R (2003) Clozapine improves deficient inhibitory auditory processing in DBA/2 mice, via a nicotinic cholinergic mechanism. Psychopharmacology 165:386–396

    PubMed  CAS  Google Scholar 

  • Smith EE, Jonides J (1999) Storage and executive processes in the frontal lobes. Science 283:1657–1661

    Article  PubMed  CAS  Google Scholar 

  • Smith RC, Warner-Cohen J, Matute M, Butler E, Kelly E, Vaidhyanathaswamy S, Khan A (2006) Effects of nicotine nasal spray on cognitive function in schizophrenia. Neuropsychopharmacology 31:637–643

    Article  PubMed  CAS  Google Scholar 

  • Steinberg ML, Williams JM, Ziedonis DM (2004) Financial implications of cigarette smoking among individuals with schizophrenia. Tob Control 13:206

    Article  PubMed  CAS  Google Scholar 

  • Stirling J, White C, Lewis S, Hopkins R, Tantam D, Huddy A, Montague L (2003) Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up study of an epidemiological cohort. Schizophr Res 65:75–86

    Article  PubMed  Google Scholar 

  • Stone JM, Davis JM, Leucht S, Pilowsky LS (2008) Cortical dopamine D2/D3 receptors are a common site of action for antipsychotic drugs—an original patient data meta-analysis of the SPECT and PET in vivo receptor imaging literature. Schizophr Bull (in press)

  • Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, Weizman A (2003) Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 60:133–141

    Article  PubMed  CAS  Google Scholar 

  • Sumiyoshi T, Matsui M, Nohara S, Yamashita I, Kurachi M, Sumiyoshi C, Jayathilake K, Meltzer HY (2001) Enhancement of cognitive performance in schizophrenia by addition of tandospirone to neuroleptic treatment. Am J Psychiatry 158:1722–1725

    Article  PubMed  CAS  Google Scholar 

  • Sumiyoshi T, Park S, Jayathilake K, Roy A, Ertugrul A, Meltzer HY (2007) Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res 95:158–168

    Article  PubMed  Google Scholar 

  • Szöke A, Trandafir A (2008) Longitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry 192:248–257

    Article  PubMed  Google Scholar 

  • Tan H, Callicott JH, Weinberger DR (2007a) Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cerebral Cortex 17Suppl 1:i171–i181

    Article  Google Scholar 

  • Tan HY, Chen Q, Goldberg TE, Mattay VS, Meyer-Lindenberg A, Weinberger DR, Callicott JH (2007b) Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory. J Neurosci 27:13393–133401

    Article  PubMed  CAS  Google Scholar 

  • Tandon R, Keshavan MS, Nasrallah HA (2008) Schizophrenia, “just the facts” what we know in 2008. 2. Epidemiology and etiology. Schizophr Res 102:1–18

    Article  PubMed  Google Scholar 

  • Terry AV Jr, Mahadik SP (2007) Time-dependent cognitive deficits associated with first and second generation antipsychotics: cholinergic dysregulation as a potential mechanism. J Pharmacol Exp Ther 320:961–968

    Article  PubMed  CAS  Google Scholar 

  • Treatment Units for Research on Neurocognition and Schizophrenia (TURNS) Retrieved December 27, 2007 from http://www.turns.ucla.edu/

  • Turner DC, Robbins RW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003) Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology 165:260–269

    PubMed  CAS  Google Scholar 

  • Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ (2004a) Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol Psychiatry 55:1031–1040

    Article  PubMed  CAS  Google Scholar 

  • Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ (2004b) Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology 29:1363–1373

    Article  PubMed  CAS  Google Scholar 

  • Varty GB, Bakshi VP, Geyer MA (1999) M100907, a serotonin 5-HT2A receptor antagonist and putative antipsychotic, blocks dizocilpine-induced prepulse inhibition deficits in Sprague–Dawley and Wistar rats. Neuropsychopharmacology 20:311–321

    Article  PubMed  CAS  Google Scholar 

  • Velligan D, Bow-Thomas CC, Mahurin R, Miller AL, Halgunseth LC (2000) Do specific neurocognitive deficits predict specific domains of function in schizophrenia? J Nerv Ment Dis 288:518–524

    Google Scholar 

  • Verdoux H, Liraud F, Assens F, Abalan F, van Os J (2002) Social and clinical consequences of cognitive deficits in early psychosis: a two-year follow-up study of first-admitted patients. Schizophr Res 56:149–159

    Article  PubMed  Google Scholar 

  • Waddington JL, Youssef HA (1996) Cognitive dysfunction in chronic schizophrenia followed prospectively over 10 years and its longitudinal relationship to the emergence of tardive dyskinesia. Psychol Med 26:681–688

    PubMed  CAS  Google Scholar 

  • Wang D, Noda Y, Zhou Y, Nitta A, Furukawa H, Nabeshima T (2007) Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission. Neuropharmacology 53:379–389

    Article  PubMed  CAS  Google Scholar 

  • Watkins P (2000) COMT inhibitors and liver toxicity. Neurology 55:S51–S52

    PubMed  CAS  Google Scholar 

  • Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann (2001) MR.5-hydroxytryptamine2A receptor inverse agonists as antipsychotics. J Pharmacol Exp Ther 299:268–276

    PubMed  CAS  Google Scholar 

  • Wezenberg E, Verkes RJ, Ruigt GS, Hulstijn W, Sabbe BG (2007) Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology 32:1272–1283

    Article  PubMed  CAS  Google Scholar 

  • Woodward ND, Jayathilake K, Meltzer HY (2007) COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr Res 90:86–96

    Article  PubMed  Google Scholar 

  • Wykes T, Reeder C, Landau S, Everitt B, Knapp M, Patel A, Romeo R (2007) A randomized controlled trial of cognitive remediation. Br J Psychiatry 190:421–427

    Article  PubMed  Google Scholar 

  • Yui K, Goto K, Ikemoto S, Ishiguro T, Angrist B, Duncan GE, Sheitman BB, Lieberman JA, Bracha SH, Ali SF (1999) Neurobiological basis of relapse prediction in stimulant-induced psychosis and schizophrenia: the role of sensitization. Mol Psychiatry 4:512–523

    Article  PubMed  CAS  Google Scholar 

  • Zoccali R, Muscatello MR, Bruno A, Cambria R, Micò U, Spina E, Meduri M (2007) The effect of lamotrigine augmentation of clozapine in a sample of treatment-resistant schizophrenic patients: a double-blind, placebo-controlled study. Schizophr Res 93:109–116

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Thank you to Stacy Bell for all her help with the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cherrie Galletly.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galletly, C. Recent advances in treating cognitive impairment in schizophrenia. Psychopharmacology 202, 259–273 (2009). https://doi.org/10.1007/s00213-008-1302-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1302-9

Keywords

Navigation