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Cognitive Factors in Schizophrenia: Causes, Impact, and Treatment

Published online by Cambridge University Press:  07 November 2014

Abstract

Greater attention has been given to the cognitive dimension in schizophrenia in recent years. This has resulted from increased recognition that cognitive impairment and negative symptoms of the disease have a greater impact on quality of life (QOL) compared to positive symptoms. Successful treatment of positive symptoms in patients with schizophrenia has not been shown to robustly translate into improvements in employment status or social relationships, while cognitive improvements are strongly associated with these important aspects of QOL and independence. These findings are based on extensive testing with standard cognitive tests for measuring executive function, verbal learning and memory, word recall, verbal working memory, spatial working memory, attention, and vigilance. Verbal learning and executive function, in particular, have been found to be valid predictors of employment success independent of the degree of severity of positive symptoms.

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Academic Supplement
Copyright
Copyright © Cambridge University Press 2004

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References

REFERENCES

1.Laruelle, M, Kegeles, LS, Abi-Dargham, A. Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci. 2003;1003:138158.Google Scholar
2.Coyle, JT, Tsai, G. The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. Psychopharmacology (Berl). 2004;174:3238.CrossRefGoogle Scholar
3.Harvey, PD, Keefe, RSE. Studies of cognitive change in patients with schizophrenia following novel anitpsychotic treatment. Am J Psychiatry. 2001;158:176184.CrossRefGoogle Scholar
4.Meltzer, HY, McGurk, SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull. 1999;25:233255.CrossRefGoogle ScholarPubMed
5.Lee, MA, Jayathilake, K, Meltzer, HY. A comparison of the effect of clozapine with typical neuroleptics on cognitive function in neuroleptic-responsive schizophrenia. Schizophr Res. 1999;37:111.Google Scholar
6.Harvey, PD, Meltzer, H, Simpson, GM, et al.Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia. Schizophr Res. 2004;66:101113.CrossRefGoogle ScholarPubMed
7.Andreasen, NC. A unitary model of schizophrenia: Bleuler's “fragmented phrene” as schizencephaly. Arch Gen Psychiatry. 1999;56:781787.Google Scholar
8.Sharma, T, Antonova, L. Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am. 2003;26:2540.Google Scholar
9.Schuepbach, D, Keshavan, MS, Kmiec, JA, Sweeney, JA. Negative symptom resolution and improvements in specific cognitive deficits after acute treatment in first-episode schizophrenia. Schizophr Res. 2002;53:249261.Google Scholar
10.Cassens, G, Inglis, AK, Appelbaum, PS, Gutheil, TG. Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull. 1990;16:477499.Google Scholar
11.Spohn, HE, Strauss, ME. Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol. 1989;98:367380.Google Scholar
12.Purdon, SE. Measuring neuropsychological change in schizophrenia with novel antipsychotic medications. J Psychiatry Neurosci. 2000;25:108116.Google ScholarPubMed
13.Crow, TJ. Positive and negative schizophrenia and their response to dopamine. Br J Psychiatry. 1980;137:383386.Google Scholar
14.Crow, TJ. The two-syndrome concept: origins and current status. Schizophr Bull. 1985;11:471486.Google Scholar
15.Johnstone, EC, Crow, TJ, Frith, CD, Husband, J, Kreel, L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976;2:924926.Google Scholar
16.Saykin, AJ, Shtasel, DL, Gur, RE, et al.Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Arch Gen Psychiatry. 1994;51:124131.CrossRefGoogle ScholarPubMed
17.Heaton, RK, Crowley, TJ. Effect of psychiatric disorders and their somatic treatments on neuropsychological test results. In: Filskov, S, Bold, TJ, eds. Handbook of Clinical Neuropsychology. New York, NY: John Wiley & Sons; 1981:481525.Google Scholar
18.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153:321330.Google Scholar
19.Breier, A, Schreiber, JL, Dyer, J, Pickar, D. National Institute of Mental Health longitudinal study of chronic schizophrenia: prognosis and predictors of outcome. Arch Gen Psychiatry. 1991;48:239246.CrossRefGoogle ScholarPubMed
20.Ho, BC, Nopoulos, P, Flaum, M, Arndt, S, Andreasen, NC. Two-year outcome in first-episode schizophrenia: predictive value of symptoms for quality of life. Am J Psychiatry. 1998;155:11961201.CrossRefGoogle ScholarPubMed
21.Robinson, DG, Woerner, MG, McMeniman, M, Mendelowitz, A, Bilder, RM. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161:473479.Google Scholar
22.Lysaker, P, Bell, M, Beam-Goulet, J. Wisconsin card sorting test and work performance in schizophrenia. Psychiatry Res. 1995;56:4551.Google Scholar
23.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(Suppl 3):27S33S.Google Scholar
24.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;25:2131.Google Scholar
25.Heaton, RK, Chelune, GJ, Lehman, RA. Using neuropsychological and personality tests to assess the likelihood of patient employment. J Nerv Ment Dis. 1978;166:408416.Google Scholar
26.McGurk, SR, Meltzer, HY. The role of cognition in vocational functioning in schizophrenia. Schizophr Res. 2000;45:175184.Google Scholar
27.Penn, DL, Mueser, KT, Spaulding, W, Hope, DA, Reed, D. Information processing and social competence in chronic schizophrenia. Schizophr Bull. 1995;21:269281.Google Scholar
28.Liberman, RP, Corrigan, PW. Designing new psychosocial treatments for schizophrenia. Psychiatry. 1993;56:238249; discussion 250-233.Google Scholar
29.Weinberger, DR, Berman, KF, Chase, TN. Mesocortical dopaminergic function and human cognition. Ann N Y Acad Sci. 1988;537:330338.CrossRefGoogle ScholarPubMed
30.Honey, GD, Bullmore, ET, Soni, W, Varatheesan, M, Williams, SC, Sharma, T. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci U S A. 1999;96:1343213437.CrossRefGoogle ScholarPubMed
31.Brozoski, TJ, Brown, RM, Rosvold, HE, Goldman, PS. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science. 1979;205:929932.Google Scholar
32.Watanabe, M, Kodama, T, Hikosaka, K. Increase of extracellular dopamine in primate prefrontal cortexs during a working memory task. J Neurophysiol. 1997;78:27952798.Google Scholar
33.Breier, A. Cognitive deficit in schizophrenia and its neurochemical basis. Br J Psychiatry Suppl. 1999(37):1618.Google Scholar
34.Breese, GR, Knapp, DJ, Moy, SS. Integrative role for serotonergic and glutamatergic receptor mechanisms in the action of NMDA antagonists: potential relationships to antipsychotic drug actions on NMDA antagonist responsiveness. Neurosci Biobehav Rev. 2002;26:441455.Google Scholar
35.Sur, C, Kinney, GG. The therapeutic potential of glycine transporter-1 inhibitors. Expert Opin Investig Drugs. 2004;13:515521.Google Scholar
36.Sumiyoshi, T, Anil, AE, Jin, D, JayatMake, K, Lee, M, Meltzer, HY. Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int J Neuropsychopharmacol. 2004;7:18.Google Scholar
37.Javitt, DC. Glycine modulators in schizophrenia. Curr Opin Investig Drugs. 2002;3:10671072.Google Scholar
38.Marcus, MM, Nomikos, GG, Svensson, TH. Differential actions of typical and atypical antipsychotic drugs on dopamine release in the core and shell of the nucleus accumbens. Eur Neuropsychopharmacol. 1996;6:2938.Google Scholar
39.Sakia, K, Gao, XM, Hashimoto, T, Tamminga, CA. Traditional and new antipsychotic drugs differentially alter neurotransmission markers in basalganglia-thalmocortical neural pathways. Synapse. 2001;39:152160.Google Scholar
40.Purdon, SE, Woodward, N, Lindborg, SR, Stip, E. Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol. Psychopharmacology (Berl). 2003;169:390397.CrossRefGoogle ScholarPubMed
41.Deutsch, JA, Hamburg, MD, Dahl, H. Anticholinesterase-induced amnesia and its temporal aspects. Science. 1966;151:221223.Google Scholar
42.Deutsch, JA. The cholinergic synapse and the site of memory. In: McGaugh, J, ed. The Chemistry of Mood, Motivation, and Memory. New York, NY: Plenum Press; 1972:187205.Google Scholar
43.Squire, LR, Glick, SD, Goldfarb, J. Relearning at different times after training as affected by centrally and peripherally acting cholinergic drugs in the mouse. J Comp Physiol Psychol. 1971;74:4145.Google Scholar
44.Minzenberg, MJ, Poole, JH, Benton, C, Vinogradov, S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry. 2004;161:116124.Google Scholar
45.Brebion, G, Bressan, RA, Amador, X, Malaspina, D, Gorman, JM. Medications and verbal memory impairment in schizophrenia: the role of anticholinergic drugs. Psychol Med. 2004;34:369374.CrossRefGoogle ScholarPubMed
46.Bymaster, FP, Calligaro, DO, Falcone, JF, et al.Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychophormacology. 1996;14:8796.CrossRefGoogle ScholarPubMed
47.Ichikawa, J, Dai, J, O'Laughlin, LA, Fowler, WL, Meltzer, HY. Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology. 2002;26:325339.Google Scholar
48.Kane, J, Honigfeld, G, Singer, J, Mekzer, H. Clozapine for the treatmentresistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789796.Google Scholar
49.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;34:702712.Google Scholar
50.Meltzer, HY, Matsubara, S, Lee, JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin 2 pKi values. J Pharmacol Exp Ther. 1989;251:238246.Google Scholar
51.Meltzer, HY, Li, Z, Kaneda, Y, Ichikawa, J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:11591172.Google Scholar
52.Millan, MJ. Improving the treatment of schizophrenia: focus on serotonin (5-HT)(1A) receptors. J Pharmacol Exp Ther. 2000;295:853861.Google Scholar
53.Kuroki, T, Meltzer, HY, Ichikawa, J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol. Exp Ther. 1999;288:774781.Google Scholar
54.Liegeois, JF, Ichikawa, J, Meltzer, HY. 5-HT(2A) receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontral cortex and inhibits that in the nucleus accumbens in a dose-dependent manner. Brain Res. 2002;947:157165.Google Scholar
55.Remington, G. Understanding antipsychotic “atypicality”: a clinical and pharmacological moving target. J Psychiatry Neurosci. 2003;28:275284.Google ScholarPubMed
56.Seeman, P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002;47:2738.Google Scholar
57.Kapur, S, Seeman, P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry. 2001;158:360369.Google Scholar
58.Roth, BL, Sheffler, D, Potkin, SG. Atypical antipsychotic drug actions: unitary or multiple mechanisms for ‘atypicality’? Clin Neurosci Res. 2003;3:108117.Google Scholar
59.Harvey, PD. Paper presented at: American Psychiatric Association 55th Institute on Psychiatric Services; October 30, 2003; Boston, Mass.Google Scholar
60.Harvey, PD, Siu, CO, Romano, S. Randomized, controlled, double-blind, multicenter comparison of the cognitive effects of ziprasidone versus olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Psychopharmocology (Berl). 2004;172:324332.Google Scholar
61.Stahl, SM, Shayegan, DK. The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 (suppl 19):612.Google Scholar
62.Stahl, SM. Psychopharmacology of Antipsychotics. London, England: Martin Dunitz Ltd.; 1999.Google Scholar
63.Schmidt, AW, Lebel, LA, Howard, HR Jr, Zorn, SH. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001;425:197201.Google Scholar
64.Shapiro, DA, Renock, S, Arrington, E, et al.Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmocology. 2003;28:14001411.Google Scholar
65.Harvey, PD. Ziprasidone and cognition: the evolving story. J Clin Psychiatry. 2003;64(suppl 19):3339.Google Scholar
66.Goff, DC, Hennen, J, Lyoo, IK, et al.Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine. Biol Psychiatry. 2002;51:493497.Google Scholar
67.Lee, MA, Thompson, PA, Meltzer, HY. Effects of clozapine on cognitive function in schizophrenia. J Clin Psychiatry. 1994;55(Suppl B):8287.Google Scholar
68.Marder, SR. Facilitating compliance with antipsychotic medication. J Clin Psychiatry. 1998;59(Suppl 3):2125.Google ScholarPubMed
69.Aguglia, E, De Vanna, M, Onor, ML, Ferrara, D. Insight in persons with schizophrenia: effects of switching from conventional neuroleptics to atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:12291233.Google Scholar
70.Siris, SG. Depression in schizophrenia: perspective in the era of “atypical” antipsychotic agents. Am J Psychiatry. 2000;157:13791389.CrossRefGoogle ScholarPubMed
71.Harvey, PD, Keefe, RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry. 2001;158:176184.Google Scholar
72.Albus, M, Hubmann, W, Ehrenberg, C, et al.Neuropsychological impairment in first-episode and chronic schizophrenic patients. Eur Arch Psychiatry Clin Neurosci. 1996;246:249255.Google Scholar
73.Bourson, A, Boess, FG, Bos, M, Sleight, AJ. Involvement of 5-HT6 receptors in nigro-striatal function in rodents. Br J Pharmacol. 1998;125:15621566.Google Scholar
74.Riemer, C, Borroni, E, Levet-Trafit, B, et al.Influence of the 5-HT6 receptor on acetylcholine release in the cortex: pharmacological characterization of 4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl) phenylamine, a potent and selective 5-HT6 receptor antagonist. J Med Chem. 2003;46:12731276.Google Scholar
75.Roth, BL, Craigo, SC, Choudhary, MS, et al.Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994;268:14031410.Google Scholar
76.Egan, MF, Weinberger, DR. Neurobiology of schizophrenia. Curr Opin Neurobiol. 1997;7:701707.Google Scholar