Cognitive Impairment in Schizophrenia

Chapter
First Online:
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 213)

Abstract

Cognitive functioning is moderately to severely impaired in patients with schizophrenia. This impairment is the prime driver of the significant disabilities in occupational, social, and economic functioning in patients with schizophrenia and an important treatment target. The profile of deficits in schizophrenia includes many of the most important aspects of human cognition: attention, memory, reasoning, and processing speed. While various efforts are under way to identify specific aspects of neurocognition that may lie closest to the neurobiological etiology and pathophysiology of the illness, and may provide relevant convergence with animal models of cognition, standard neuropsychological measures continue to demonstrate the greatest sensitivity to functionally relevant cognitive impairment.

The effects of antipsychotic medications on cognition in schizophrenia and first-episode psychosis appear to be minimal. Important work on the effects of add-on pharmacologic treatments is ongoing. Very few of the studies completed to date have had sufficient statistical power to generate firm conclusions; recent studies examining novel add-on treatments have produced some encouraging findings. Cognitive remediation programs have generated considerable interest as these methods are far less costly than pharmacologic treatment and are likely to be safer. A growing consensus suggests that these interventions produce modest gains for patients with schizophrenia, but the efficacy of the various methods used has not been empirically investigated.

Keywords

Cognition Neurocognition Neuropsychology Cognitive neuroscience Memory Attention Processing speed Executive functioning Social cognition Cognitive remediation Enhancement 
This is a preview of subscription content, log in to check access

References

  1. Addington J, Addington D (1998) Facial affect recognition and information processing in schizophrenia and bipolar disorder. Schizophr Res 32:171–181PubMedCrossRefGoogle Scholar
  2. Addington J, Addington D (2000) Neurocognitive and social functioning in schizophrenia: a 2.5 year follow-up study. Schizophr Res 44:47–56PubMedCrossRefGoogle Scholar
  3. Addington J, Addington D, Maticka-Tyndale E (1991) Cognitive functioning and positive and negative symptoms in schizophrenia. Schizophr Res 5:123–134PubMedCrossRefGoogle Scholar
  4. Aleman A, Hijman R, de Haan EH, Kahn RS (1999) Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry 156:1358–1366PubMedGoogle Scholar
  5. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders DSM-IV-TR, Text Revision 4th edn. American Psychiatric Association, Washington, DC, ISBN 0-89042-024-6Google Scholar
  6. Baddeley A (1992) Working memory. Science 255:556–559, ReviewPubMedCrossRefGoogle Scholar
  7. Barch DM, Keefe RSE (2010) Anticipating DSM-V: Opportunities and challenges for cognition and psychosis. Schizophr Bull 36:43–47PubMedCrossRefGoogle Scholar
  8. Bell MD, Bryson G (2001) Work rehabilitation in schizophrenia: does cognitive impairment limit improvement? Schizophr Bull 27:269–279PubMedCrossRefGoogle Scholar
  9. Bell MD, Greig TC, Kaplan E, Bryson G (1997) Wisconsin Card Sorting Test dimensions in schizophrenia: factorial, predictive, and divergent validity. J Clin Exp Neuropsychol 19:933–941PubMedCrossRefGoogle Scholar
  10. Bilder RM, Mukherjee S, Rieder RO, Pandurangi AK (1985) Symptomatic and neuropsychological components of defect states. Schizophr Bull 11:409–419PubMedCrossRefGoogle Scholar
  11. Brekke JS, Long JD, Nesbitt N, Sobel E (1997) The impact of service characteristics on functional outcomes from community support programs for persons with schizophrenia: a growth curve analysis. J Consult Clin Psychol 65:464–475PubMedCrossRefGoogle Scholar
  12. Brekke JS, Kohrt B, Green MF (2001) Neuropsychological functioning as a moderator of the relationship between psychosocial functioning and the subjective experience of self and life in schizophrenia. Schizophr Bull 27:697–708PubMedCrossRefGoogle Scholar
  13. Brekke JS, Hoe M, Long J, Green MF (2007) How neurocognition and social cognition influence functional change during community-based psychosocial rehabilitation for individuals with schizophrenia. Schizophr Bull 33:1247–1256PubMedCrossRefGoogle Scholar
  14. Bressi S, Miele L, Bressi C et al (1996) Deficit of central executive component of working memory in schizophrenia. New Trends Exp Clin Psychiatry 12:243–252Google Scholar
  15. Brewer WJ, Wood SJ, McGorry PD, Francey SM, Phillips LJ, Yung AR, Anderson V, Copolov DL, Singh B, Velakoulis D, Pantelis C (2003) Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia. Am J Psychiatry 160:1790–1794PubMedCrossRefGoogle Scholar
  16. Brewer WJ, Francey SM, Wood SJ, Jackson HJ, Pantelis C, Phillips LJ, Yung AR, Anderson VA, McGorry PD (2005) Memory impairments identified in people at ultra-high risk for psychosis who later develop first episode psychosis. Am J Psychiatry 162:71–78PubMedCrossRefGoogle Scholar
  17. Buchanan RW, Holstein C, Breier A (1994) The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance. Biol Psychiatry 36:717–725PubMedCrossRefGoogle Scholar
  18. Buchanan RW, Davis M, Goff D, Green MF, Keefe RS, Leon AC, Nuechterlein KH, Laughren T, Levine R, Stover E, Fenton W, Marder SR (2005) A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 31:5–19PubMedCrossRefGoogle Scholar
  19. Buchanan RW, Keefe RS, Umbricht D, Green MF, Laughren T, Marder SR (2011a) The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: What do we know 5 years later? Schizophr Bull 37:1209–1017PubMedCrossRefGoogle Scholar
  20. Buchanan RW, Keefe RS, Lieberman JA, Barch DM, Csernansky JG, Goff DC, Gold JM, Green MF, Jarskog LF, Javitt DC, Kimhy D, Kraus MS, McEvoy JP, Mesholam-Gately RI, Seidman LJ, Ball MP, McMahon RP, Kern RS, Robinson J, Marder SR (2011b) A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry 69:442–449PubMedCrossRefGoogle Scholar
  21. Burdick KE, Goldberg TE, Cornblatt BA, Keefe RS, Gopin CB, Derosse P, Braga RJ, Malhotra AK (2011) The MATRICS consensus cognitive battery in patients with bipolar I disorder. Neuropsychopharmacology 36:1587–1592PubMedCrossRefGoogle Scholar
  22. Callicott JH, Mattay VS, Bertolino A, Finn K, Coppola R, Frank JA, Goldberg TE, Weinberger DR (1999) Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex 9:20–26PubMedCrossRefGoogle Scholar
  23. Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, Walker E, Seidman LJ, Perkins D, Tsuang M, McGlashan T, Heinssen R (2008) Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiatry 65:28–37PubMedCrossRefGoogle Scholar
  24. Carter CS, Barch DM (2007) Cognitive neuroscience-based approaches to measuring and improving treatment effects on cognition in schizophrenia: the CNTRICS initiative. Schizophr Bull 33:1131–1137PubMedCrossRefGoogle Scholar
  25. Carter C, Robertson L, Nordahl T, Chaderjian M, Kraft L, O’Shora-Celaya L (1996) Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients. Biol Psychiatry 40:930–932PubMedCrossRefGoogle Scholar
  26. 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 64:4–10PubMedCrossRefGoogle Scholar
  27. Caspi A, Reichenberg A, Weiser M, Rabinowitz J, Kaplan Z, Knobler H, Davidson-Sagi N, Davidson M (2003) Cognitive performance in schizophrenia patients assessed before and following the first psychotic episode. Schizophr Res 65:87–94PubMedCrossRefGoogle Scholar
  28. Corcoran R, Mercer G, Frith CD (1995) Schizophrenia, symptomatology and social inference: investigating “theory of mind” in people with schizophrenia. Schizophr Res 17:5–13PubMedCrossRefGoogle Scholar
  29. Corrigan PW, Liberman RP, Engel JD (1990) From noncompliance to collaboration in the treatment of schizophrenia. Hosp Commun Psychiatry 41:1203–1211Google Scholar
  30. David AS, Malmberg A, Brandt L, Allebeck P, Lewis G (1997) IQ and risk for schizophrenia: A population-based cohort study. Psychol Med 27:1311–1323PubMedCrossRefGoogle Scholar
  31. Davidson M, Harvey PD, Powchik P, Parrella M, White L, Knobler HY, Losonczy MF, Keefe RS, Frecska E (1995) Severity of symptoms in chronically institutionalized geriatric schizophrenic patients. Am J Psychiatry 152:197–207PubMedGoogle Scholar
  32. Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M (1999) Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 156:1328–1335PubMedGoogle Scholar
  33. Davis SM, Koch GG, Davis CE, LaVange LM (2003) Statistical approaches to effectiveness measurement and outcome-driven re-randomizations in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies. Schizophr Bull 29:73–80PubMedCrossRefGoogle Scholar
  34. Dias EC, Butler PD, Hoptman MJ, Javitt DC (2011) Early sensory contributions to contextual encoding deficits in schizophrenia. Arch Gen Psychiatry 68:654–664PubMedCrossRefGoogle Scholar
  35. 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 37:13–20PubMedCrossRefGoogle Scholar
  36. Dickinson D, Ramsey ME, Gold JM (2007) Overlooking the obvious: A meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch Gen Psychiatry 64:532–542PubMedCrossRefGoogle Scholar
  37. Donohoe G, Owens N, O’Donnell C, Burke T, Moore L, Tobin A, O’Callaghan E (2001) Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: A discriminant function analysis. Eur Psychiatry 16:293–298PubMedCrossRefGoogle Scholar
  38. Drury VM, Robinson EJ, Birchwood M (1998) Theory of mind skills during an acute episode of psychosis and following recovery. Psychol Med 28:1101–1112PubMedCrossRefGoogle Scholar
  39. Edwards J, Pattison PE, Jackson HJ, Wales RJ (2001) Facial affect and affective prosody recognition in first-episode schizophrenia. Schizophr Res 48:235–253PubMedCrossRefGoogle Scholar
  40. Ertuğrul A, Uluğ B (2002) The influence of neurocognitive deficits and symptoms on disability in schizophrenia. Acta Psychiatr Scand 105:196–201PubMedCrossRefGoogle Scholar
  41. Evans JD, Heaton RK, Paulsen JS, Palmer BW, Patterson T, Jeste DV (2003) The relationship of neuropsychological abilities to specific domains of functional capacity in older schizophrenic patients. Biol Psychiatry 53:422–430PubMedCrossRefGoogle Scholar
  42. Fenton WS, Blyler CR, Heinssen RK (1997) Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull 23:637–651PubMedCrossRefGoogle Scholar
  43. Friedman L (2002) Psychoanalysis: practice and technique. J Am Psychoanal Assoc 50:727–732PubMedCrossRefGoogle Scholar
  44. Fuller R, Nopoulos P, Arndt S, O’Leary D, Ho BC, Andreasen NC (2002) Longitudinal assessment of premorbid cognitive functioning in patients with schizophrenia through examination of standardized scholastic test performance. Am J Psychiatry 159:1183–1189PubMedCrossRefGoogle Scholar
  45. Gaebel W, Wölwer W (1992) Facial expression and emotional face recognition in schizophrenia and depression. Eur Arch Psychiatry Clin Neurosci 242:46–52PubMedCrossRefGoogle Scholar
  46. George TP, Ziedonis DM, Feingold A, Pepper WT, Satterburg CA, Winkel J, Rounsaville BJ, Kosten TR (2000) Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. Am J Psychiatry 157:1835–1842PubMedCrossRefGoogle Scholar
  47. Gold JM, Goldberg RW, McNary SW, Dixon LB, Lehman AF (2002) Cognitive correlates of job tenure among patients with severe mental illness. Am J Psychiatry 159:1395–1402PubMedCrossRefGoogle Scholar
  48. Gold JM, Wilk CM, McMahon RP, Buchanan RW, Luck SJ (2003) Working memory for visual features and conjunctions in schizophrenia. J Abnorm Psychol 112:61–71PubMedCrossRefGoogle Scholar
  49. Goldberg TE, Weinberger DR, Berman KF, Pliskin NH, Podd MH (1987) Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry 44:1008–1014PubMedCrossRefGoogle Scholar
  50. Goldberg TE, Ragland JD, Torrey EF, Gold JM, Bigelow LB, Weinberger DR (1990) Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Arch Gen Psychiatry 47:1066–1072PubMedCrossRefGoogle Scholar
  51. Goldman-Rakic PS (1987) Circuitry of the frontal association cortex and its relevance to dementia. Arch Gerontol Geriatr 6:299–309PubMedCrossRefGoogle Scholar
  52. Goldman-Rakic PS (1994) Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 6:348–357PubMedGoogle Scholar
  53. Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330PubMedGoogle Scholar
  54. 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, ReviewPubMedCrossRefGoogle Scholar
  55. Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, Fenton WS, Frese F, Goldberg TE, Heaton RK, Keefe RSE, Kern RS, Kraemer H, Stover E, Weinberger DR, Zalcman S, Marder SR (2004) Approaching a consensus cognitive battery for clinical trials in schizophrenia: The NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry 56:301–307PubMedCrossRefGoogle Scholar
  56. Green MF, Schooler NR, Kern RS, Frese FJ, Granberry W, Harvey PD, Karson CN, Peters N, Stewart M, Seidman LJ, Sonnenberg J, Stone WS, Walling D, Stover E, Marder SR (2011) Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia. Am J Psychiatry 168:400–407PubMedCrossRefGoogle Scholar
  57. Harvey PD, Keefe RSE (1997) Cognitive impairment in schizophrenia and implications of atypical neuroleptic treatment. CNS Spectrums 2:1–11Google Scholar
  58. 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 162:1888–1895PubMedCrossRefGoogle Scholar
  59. Harvey PD, Velligan DI, Bellack AS (2007) Performance-based measures of functional skills: usefulness in clinical treatment studies. Schizophr Bull 33:1138–1148PubMedCrossRefGoogle Scholar
  60. Hawkins KA, Addington J, Keefe RS, Christensen B, Perkins DO, Zipursky R, Woods SW, Miller TJ, Marquez E, Breier A, McGlashan TH (2004) Neuropsychological status of subjects at high risk for a first episode of psychosis. Schizophr Res 67:115–122PubMedCrossRefGoogle Scholar
  61. Heaton RK, Pendleton MG (1981) Use of Neuropsychological tests to predict adult patients’ everyday functioning. J Consult Clin Psychol 49:807–821PubMedCrossRefGoogle Scholar
  62. Heinrichs RW, Zakzanis KK (1998) Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12:426–445PubMedCrossRefGoogle Scholar
  63. Hyman SE, Fenton WS (2003) Medicine. What are the right targets for psychopharmacology? Science 299:350–351PubMedCrossRefGoogle Scholar
  64. Jarboe KS, Schwartz SK (1999) The relationship between medication noncompliance and cognitive function in patients with schizophrenia. J Am Psychiatr Nurses Assoc 5:S2–S8CrossRefGoogle Scholar
  65. Jeste SD, Patterson TL, Palmer BW, Dolder CR, Goldman S, Jeste DV (2003) Cognitive predictors of medication adherence among middle-aged and older outpatients with schizophrenia. Schizophr Res 63:49–58PubMedCrossRefGoogle Scholar
  66. Jones P, Rodgers B, Murray R, Marmot M (1994) Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344:1398–1402PubMedCrossRefGoogle Scholar
  67. Keefe RSE (1995) The contribution of neuropsychology to psychiatry. Am J Psychiatry 152:6–15PubMedGoogle Scholar
  68. Keefe RSE (2000) Working memory dysfunction and its relevance in schizophrenia. In: Sharma T, Harvey PD (eds) Cognition in schizophrenia: characteristics, correlates, and treatment. Oxford University Press, Oxford, pp 16–49Google Scholar
  69. Keefe RSE, Fenton WS (2007) How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull 33:912–920PubMedCrossRefGoogle Scholar
  70. Keefe RSE, Harvey PD (2008) Implementation considerations for multi-site clinical trials with cognitive neuroscience tasks. Schizophr Bull 34:656–663PubMedCrossRefGoogle Scholar
  71. Keefe RSE, Kraus MS (2009) Measuring memory-prediction errors and their consequences in youth at risk for schizophrenia. Ann Acad Med Sing 38:414–416Google Scholar
  72. Keefe RSE, Arnold MC, Bayen UJ, McEvoy JP, Wilson WH (2002) Source monitoring deficits for self-generated stimuli in schizophrenia: Multinomial modeling of data from three sources. Schizophr Res 57:51–67PubMedCrossRefGoogle Scholar
  73. Keefe RSE, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Lewine RR, Yurgelun-Todd DA, Gur RC, Tohen M, Tollefson GD, Sanger TM, Lieberman JA (2004) Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: A randomized double-blind trial of olanzapine versus low-doses of haloperidol. Am J Psychiatry 161:985–99PubMedCrossRefGoogle Scholar
  74. Keefe RSE, Eesley CE, Poe M (2005) Defining a cognitive function decrement in schizophrenia. Biol Psychiatry 57:688–691PubMedCrossRefGoogle Scholar
  75. Keefe RSE, Bilder RM, Harvey PD, Sm D, Palmer BW, Gold JM, Meltzer HY, Green MF, Miller DD, Canive JM, Adler LW, Manschreck TC, Swartz M, Rosenheck R, Perkins DO, Walker TM, Stroup TS, McEvoy JP, Lieberman JA (2006a) Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology 31:2033–2046PubMedCrossRefGoogle Scholar
  76. Keefe RSE, Perkins DO, Gu H, Zipursky RB, Christensen BK, Lieberman JA (2006b) A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophr Res 88:26–35PubMedCrossRefGoogle Scholar
  77. Keefe RSE, 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, Hasiao 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 64:633–647PubMedCrossRefGoogle Scholar
  78. Keefe RSE, Malhotra AK, Meltzer H, Kane JM, Buchanan RW, Murthy A, Sovel M, Li C, Goldman R (2007b) 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 33:1217–1228PubMedCrossRefGoogle Scholar
  79. Keefe RSE, Fox KH, Harvey PD, Cucchiaro J, Siu C, Loebel A (2011a) Characteristics of the MATRICS consensus cognitive battery in a 29 site antipsychotic schizophrenia clinical trial. Schizophr Res 125:161–168PubMedCrossRefGoogle Scholar
  80. Keefe RSE, Kraus MS, Krishnan RR (2011b) Failures in learning-dependent predictive perception as the key cognitive vulnerability to psychosis in schizophrenia. Neuropsychopharmacology 36:367–380PubMedCrossRefGoogle Scholar
  81. Keefe R, Buchanan R, Marder S et al (2011c) Clinical trials of potential cognitive-enhancing drugs in schizophrenia: What have we learned so far? Annual Meeting of NCDEU, Boca Raton, FLGoogle Scholar
  82. Keefe RSE, Vinogradov S, Medalia A, Silverstein SM, Bell MD, Dickinson D, Ventura J, Marder SR, Stroup TS (2011d) Report from the Working Group Conference on multi-site trial design for cognitive remediation in schizophrenia. Schizophr Bull 37:1057–1065PubMedCrossRefGoogle Scholar
  83. Keefe RSE, Vinogradov S, Medalia A, Buckley PF, Caroff SN, d’Souza DC, Harvey PD, Graham KA, Hamer RM, Marder SM, Miller DD, Olson SJ, Patel JK, Velligan D, Walker TM, Haim AJ, Stroup TS (2012) Feasibility and pilot efficacy results from the multi-site Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) study. J Clin Psychiatry 73:1016–1022Google Scholar
  84. Kern RS, Nuechterlein KH, Green MF, Baade LE, Fenton WS, Gold JM, Keefe RS, 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 165:214–220PubMedCrossRefGoogle Scholar
  85. Kraemer HC, Frank E (2010) Evaluation of comparative treatment trials: assessing clinical benefits and risks for patients, rather than statistical effects on measures. J Am Med Assoc 304:683–684CrossRefGoogle Scholar
  86. Kraus MS, Keefe RSE, Krishnan RK (2009) Memory-prediction errors and their consequences in schizophrenia. Neuropsychol Rev 19:336–352PubMedCrossRefGoogle Scholar
  87. Kremen WS, Seidman LJ, Faraone SV, Toomey R, Tsuang MT (2000) The paradox of normal neuropsychological function in schizophrenia. J Abnorm Psychol 109:743–752PubMedCrossRefGoogle Scholar
  88. Krishnan RR, Fivaz M, Kraus M, Keefe RSE (2011a) Hierarchical temporal processing deficit model of reality distortion and psychoses. Mol Psychiatry 16:129–144PubMedCrossRefGoogle Scholar
  89. Krishnan RR, Kraus MS, Keefe RSE (2011b) Comprehensive model of how reality distortion and symptoms occur in schizophrenia. Could impairment in learning-dependent predictive perception account for the manifestations of schizophrenia? Psychiatry Clin Neurosci 65:305–317PubMedCrossRefGoogle Scholar
  90. Leung WW, Bowi CR, Harvey PD (2008) Functional implications of neuropsychological normality and symptom remission in older outpatients diagnosed with schizophrenia: A cross-sectional study. J Int Neuropsychol Soc 14:479–488PubMedCrossRefGoogle Scholar
  91. Lysaker P, Bell M (1995) Work rehabilitation and improvements in insight in schizophrenia. J Nerv Ment Dis 183:103–106PubMedCrossRefGoogle Scholar
  92. Malla AK, Norman RM, Manchanda R, Townsend L (2002) Symptoms, cognition, treatment adherence and functional outcome in first-episode psychosis. Psychol Med 32:1109–1119PubMedCrossRefGoogle Scholar
  93. Mausbach BT, Bowie CR, Harvey PD, Twamley EW, Goldman SR, Jeste DV, Patterson TL (2008) Usefulness of the UCSD performance-based skills assessment (UPSA) for predicting residential independence in patients with chronic schizophrenia. J Psychiatr Res 42:320–327PubMedCrossRefGoogle Scholar
  94. McClure MM, Bowie CR, Patterson TL, Heaton RK, Weaver C, Anderson H, Harvey PD (2007) Correlations of functional capacity and neuropsychological performance in older patients with schizophrenia: evidence for specificity of relationships? Schizophr Res 89:330–338PubMedCrossRefGoogle Scholar
  95. McGurk SR, Meltzer HY (2000) The role of cognition in vocational functioning in schizophrenia. Schizophr Res 45:175–184PubMedCrossRefGoogle Scholar
  96. McGurk SR, Mueser KT, Harvey PD, LaPuglia R, Marder J (2003) Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment. Psychiatr Serv 54:1129–1135PubMedCrossRefGoogle Scholar
  97. McGurk SR, Mueser KT, Feldman K, Wolfe R, Pascaris A (2007a) Cognitive training for supported employment: 2–3 year outcomes of a randomized controlled trial. Am J Psychiatry 164:437–441PubMedCrossRefGoogle Scholar
  98. McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT (2007b) A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry 164:1791–1802PubMedCrossRefGoogle Scholar
  99. Mohamed S, Paulsen JS, O’Leary D, Arndt S, Andreasen N (1999) Generalized cognitive deficits in schizophrenia: A study of first-episode patients. Arch Gen Psychiatry 56:749–754PubMedCrossRefGoogle Scholar
  100. Mohamed S, Rosenheck R, Swartz M, Stroup S, Lieberman JA, Keefe RS (2008) Relationship of cognition and psychopathology to functional impairment in schizophrenia. Am J Psychiatry 165:978–987PubMedCrossRefGoogle Scholar
  101. Morrison RL, Bellack AS, Mueser KT (1988) Deficits in facial-affect recognition and schizophrenia. Schizophr Bull 14:67–83, ReviewPubMedCrossRefGoogle Scholar
  102. Mueser KT, Bellack AS, Douglas MS, Wade JH (1991) Prediction of social skill acquisition in schizophrenic and major affective disorder patients from memory and symptomatology. Psychiatry Res 37:281–296PubMedCrossRefGoogle Scholar
  103. 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, ReviewPubMedCrossRefGoogle Scholar
  104. Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ III, 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 165:203–213PubMedCrossRefGoogle Scholar
  105. Palmer BW, Heaton RK, Paulsen JS, Kuck J, Braff D, Harris MJ, Zisook S, Jeste DV (1997) Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology 11:437–446PubMedCrossRefGoogle Scholar
  106. Patterson TL, Goldman S, McKibbin CL, Hughs T, Jeste DV (2001) UCSD Performance-Based Skills Assessment: development of a new measure of everyday functioning for severely mentally ill adults. Schizophr Bull 27:235–245PubMedCrossRefGoogle Scholar
  107. Patterson TL, Lacro J, McKibbin CL, Moscona S, Hughs T, Jeste DV (2002) Medication management ability assessment: results from a performance-based measure in older outpatients with schizophrenia. J Clin Psychopharmacol 22:11–19PubMedCrossRefGoogle Scholar
  108. Penn DL, Spaulding W, Reed D, Sullivan M (1996) The relationship of social cognition to ward behavior in chronic schizophrenia. Schizophr Res 20:327–335PubMedCrossRefGoogle Scholar
  109. Penn DL, Corrigan PW, Bentall RP, Racenstein JM, Newman L (1997) Social cognition in schizophrenia. Psychol Bull 121:114–132PubMedCrossRefGoogle Scholar
  110. Pinkham AE, Loughead J, Ruparel K, Overton E, Gur RE, Gur RC (2011) Abnormal modulation of amygdala activity in schizophrenia in response to direct- and averted-gaze threat-related facial expressions. Am J Psychiatry 168:293–301PubMedCrossRefGoogle Scholar
  111. Reichenberg A, Harvey PD, Bowie CR, Mojtabai R, Rabinowitz J, Heaton RK, Bromet E (2009) Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Schizophr Bull 35:1022–1029PubMedCrossRefGoogle Scholar
  112. Reichenberg A, Caspi A, Harrington H, Houts R, Keefe RS, Murray RM, Poulton R, Moffitt TE (2010) Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: A 30-year study. Am J Psychiatry 167:160–169PubMedCrossRefGoogle Scholar
  113. Reilly JL, Harris MSH, Keshavan MS, Sweeney JA (2006) Adverse effects of risperidone on spatial working memory in first-episode schizophrenia. Arch Gen Psychiatry 63:1189–1197PubMedCrossRefGoogle Scholar
  114. Rosenheck R, Doyle J, Leslie D, Fontana A (2003) Changing environments and alternative perspectives in evaluating the cost-effectiveness of new antipsychotic drugs. Schizophr Bull 29:81–93PubMedCrossRefGoogle Scholar
  115. Sarfati Y, Hardy-Bayle MC, Nadel J et al (1997) Attribution of mental states to others by schizophrenic patients. Cogn Neuropsychiatr 2:1–17CrossRefGoogle Scholar
  116. Saykin AJ, Gur RC, Gur RE, Mozley PD, Mozley LH, Resnick SM, Kester DB, Stafiniak P (1991) Neuropsychological function in schizophrenia. Selective impairment in memory and learning. Arch Gen Psychiatry 48:618–624PubMedCrossRefGoogle Scholar
  117. Seidman LJ, Giuliano AJ, Meyer EC, Addington J, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, Tsuang MT, Walker EF, Woods SW, Bearden CE, Christensen BK, Hawkins K, Heaton R, Keefe RS, Heinssen R, Cornblatt BA, North American Prodrome Longitudinal Study (NAPLS) Group (2010) Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch Gen Psychiatry 67:578–588PubMedCrossRefGoogle Scholar
  118. Sevy S, Davidson M (1995) The cost of cognitive impairment in schizophrenia. Schizophr Res 17:1–3PubMedCrossRefGoogle Scholar
  119. Silver H, Feldman P, Bilker W, Gur RC (2003) Working memory deficit as a core neuropsychological dysfunction in schizophrenia. Am J Psychiatry 160:1809–1816PubMedCrossRefGoogle Scholar
  120. Strauss ME (1993) Relations of symptoms to cognitive deficits in schizophrenia. Schizophr Bull 19:215–231, ReviewPubMedCrossRefGoogle Scholar
  121. Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, Perkins DO, Keefe RS, Davis CE, Severe J, Hsiao JK, Investigators CATIE (2006) Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia after discontinuing a previous atypical antipsychotic. Am J Psychiatry 13:611–622CrossRefGoogle Scholar
  122. Swartz MS, Perkins DO, Stroup TS, McEvoy JP, Nieri JM, Haak DC (2003) Assessing clinical and functional outcomes in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Schizophr Bull 29:33–43PubMedCrossRefGoogle Scholar
  123. Sweet RA, Pollock BG, Mulsant BH, Rosen J, Sorisio D, Kirshner M, Henteleff R, DeMichele MA (2000) Pharmacologic Profile of Perphenazine’s Metabolites. J Clin Psychopharmacol 20:181–187PubMedCrossRefGoogle Scholar
  124. Tamlyn D, McKenna PJ, Mortimer AM, Lund CE, Hammond S, Baddeley AD (1992) Memory impairment in schizophrenia: Its extent, affiliations and neuropsychological character. Psychol Med 22:101–115PubMedCrossRefGoogle Scholar
  125. Tan HY, Choo WC, Fones CS, Chee MW (2005) fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. Am J Psychiatry 162:1849–1858PubMedCrossRefGoogle Scholar
  126. Trumbetta SL, Mueser KT (2001) Social functioning and its relationship to cognitive deficits over the course of schizophrenia. In: Keefe RSE, McEvoy JP (eds) Negative Symptom and Cognitive Deficit Treatment Response in Schizophrenia. American Psychiatric Association, Washington, DC, pp 33–67Google Scholar
  127. Twamley EW, Doshi RR, Nayak GV, Palmer BW, Golshan S, Heaton RK, Patterson TL, Jeste DV (2003) Generalized cognitive impairments, ability to perform everyday tasks, and level of independence in community living situations of older patients with psychosis. Am J Psychiatry 159:2013–2020CrossRefGoogle Scholar
  128. Van Putten T, Marder SR, Wirshing WC, Aravagiri M, Chabert N (1991) Neuroleptic plasma levels. Schizophr Bull 17:197–216PubMedCrossRefGoogle Scholar
  129. Velligan DI, Bow-Thomas CC, Mahurin RK, Miller AL, Halgunseth LC (2000) Do specific neurocognitive deficits predict specific domains of community function in schizophrenia? J Nerv Ment Dis 188:518–524PubMedCrossRefGoogle Scholar
  130. Walker E, Lewine RJ (1988) The positive/negative symptom distinction in schizophrenia. Validity and etiological relevance. Schizophr Res 1:315–328PubMedCrossRefGoogle Scholar
  131. Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669PubMedCrossRefGoogle Scholar
  132. Wykes T, Reeder C, Corner J, Williams C, Everitt B (1999) The effects of neurocognitive remediation on executive processing in patients with schizophrenia. Schizophr Bull 25:291–307PubMedCrossRefGoogle Scholar
  133. Yung AR, McGorry PD (1996) The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophr Bull 22:353–370PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Duke University Medical CenterDurhamUSA
  2. 2.University of Miami Miller School of MedicineMiamiUSA

Personalised recommendations