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Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia

  • Maren Carbon (a1) and Christoph U. Correll (a1) (a2) (a3) (a4)

Since currently available antipsychotic medications predominantly treat hallucinations, delusions, disorganized thoughts and behavior, and related agitation/aggression, attention has traditionally been focused on managing positive symptoms. However, prominent negative symptoms and clinically relevant cognitive impairment affect approximately 40% and 80% of people with schizophrenia, respectively. Moreover, negative and cognitive symptoms are closely related to functional outcomes, and contribute substantially to the overall illness burden. Therefore, approaches to describe, measure, and manage these symptom domains are relevant. This article summarizes the phenomenology, prevalence, assessment, and treatment of negative and cognitive symptoms in patients with schizophrenia, including pharmacologic and nonpharmacologic management strategies that can be used in clinical care now, as well as pharmacologic approaches that are being tested. Currently, no approved treatments targeting negative or cognitive symptomatology in schizophrenia are available. It is hoped that progress in the understanding of the neurobiology of these important symptom domains of schizophrenia will help develop effective treatment strategies in the future. However, until this goal is achieved, clinicians should avoid therapeutic nihilism. Rather, the severity and impact of negative and cognitive symptoms should be determined, quantified, and monitored. Further, psychosocial treatments have shown therapeutic benefits. Thus, cognitive behavioral therapy, cognitive remediation, social skills training, and computer-assisted training programs should be offered in conjunction with antipsychotic treatment. Several non-antipsychotic augmentation strategies can be tried off-label. Treatment plans that incorporate currently available management options for negative and cognitive symptomatology in patients with schizophrenia should be adapted over time and based on the individual’s needs, with the aim to enhance overall outcomes.

Corresponding author
*Address for correspondence: Christoph U. Correll, MD, The Zucker Hillside Hospital, Psychiatry, 75-59 263rd Street, Glen Oaks, NY 11004, USA. (Email:
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This activity is supported by an educational grant from Envivo Pharmaceuticals, LLC (a.k.a. FORUM Pharmaceuticals, Inc)

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1.Kirkpatrick, B, Strauss, GP, Nguyen, L, et al. The brief negative symptom scale: psychometric properties. Schizophr Bull. 2011; 37(2): 300305.
2.Blanchard, JJ, Cohen, AS. The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr Bull. 2006; 32(2): 238245.
3.Kring, AM, Gur, RE, Blanchard, JJ, Horan, WP, Reise, SP. The Clinical Assessment Interview for Negative Symptoms (CAINS): final development and validation. Am J Psychiatry. 2013; 170(2): 165172.
4.Foussias, G, Remington, G. Negative symptoms in schizophrenia: avolition and Occam's razor. Schizophr Bull. 2010; 36(2): 359369.
5.Pizzagalli, DA. The “anhedonia paradox” in schizophrenia: insights from affective neuroscience. Biol Psychiatry. 2010; 67(10): 899901.
6.Cohen, AS, Minor, KS. Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophr Bull. 2010; 36(1): 143150.
7.Buchanan, RW. Persistent negative symptoms in schizophrenia: an overview. Schizophr Bull. 2007; 33(4): 10131022.
8.Kinon, BJ, Noordsy, DL, Liu-Seifert, H, Gulliver, AH, Ascher-Svanum, H, Kollack-Walker, S. Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning. J Clin Psychopharmacol. 2006; 26(5): 453461.
9.Rabinowitz, J, Berardo, CG, Bugarski-Kirola, D, Marder, S. Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis. Schizophr Res. 2013; 150(2–3): 339342.
10.Levine, SZ, Leucht, S. Identifying clinically meaningful symptom response cut-off values on the SANS in predominant negative symptoms. Schizophr Res. 2013; 145(1–3): 125127.
11.Galderisi, S, Maj, M. Deficit schizophrenia: an overview of clinical, biological and treatment aspects. Eur Psychiatry. 2009; 24(8): 493500.
12.Correll, CU, Kishimoto, T, Nielsen, J, Kane, JM. Quantifying clinical relevance in the treatment of schizophrenia. Clin Ther. 2011; 33(12): B16B39.
13.Kane, JM. Tools to assess negative symptoms in schizophrenia. J Clin Psychiatry. 2013; 74(6): e12.
14.Selten, JP, Wiersma, D, van den Bosch, RJ. Discrepancy between subjective and objective ratings for negative symptoms. J Psychiatr Res. 2000; 34(1): 1113.
15.Marder, SR, Alphs, L, Anghelescu, IG, et al. Issues and perspectives in designing clinical trials for negative symptoms in schizophrenia. Schizophr Res. 2013; 150(2–3): 328333.
16.Alphs, L, Summerfelt, A, Lann, H, Muller, RJ. The Negative Symptom Assessment: a new instrument to assess negative symptoms of schizophrenia. Psychopharmacol Bull. 1989; 25(2): 159163.
17.Alphs, L, Morlock, R, Coon, C, Cazorla, P, Szegedi, A, Panagides, J. Validation of a 4-item Negative Symptom Assessment (NSA-4): a short, practical clinical tool for the assessment of negative symptoms in schizophrenia. Int J Methods Psychiatr Res. 2011; 20(2): e31e37.
18.Forbes, C, Blanchard, JJ, Bennett, M, Horan, WP, Kring, A, Gur, R. Initial development and preliminary validation of a new negative symptom measure: the Clinical Assessment Interview for Negative Symptoms (CAINS). Schizophr Res. 2010; 124(1–3): 3642.
19.Strauss, GP, Keller, WR, Buchanan, RW, et al. Next-generation negative symptom assessment for clinical trials: validation of the Brief Negative Symptom Scale. Schizophr Res. 2012; 142(1–3): 8892.
20.Bobes, J, Arango, C, Garcia-Garcia, M, Rejas, J; CLAMORS Study Collaborative Group. Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J Clin Psychiatry. 2010; 71(3): 280286.
21.Strauss, GP, Horan, WP, Kirkpatrick, B, Fischer, BA, Keller, WR, Miski, P, Buchanan, RW, Green, MF, Carpenter, WT Jr. Deconstructing negative symptoms of schizophrenia: avolition-apathy and diminished expression clusters predict clinical presentation and functional outcome. J Psychiatr Res. 2013; 47(6): 783790.
22.Peralta, V, Cuesta, MJ. Dimensional structure of psychotic symptoms: an item-level analysis of SAPS and SANS symptoms in psychotic disorders. Schizophr Res. 1999; 38(1): 1326.
23.Lyne, J, O'Donoghue, B, Owens, E, et al. Prevalence of item level negative symptoms in first episode psychosis diagnoses. Schizophr Res. 2012; 135(1–3): 128133.
24.Fulford, D, Niendam, TA, Floyd, EG, et al. Symptom dimensions and functional impairment in early psychosis: more to the story than just negative symptoms. Schizophr Res. 2013; 147(1): 125131.
25.Fusar-Poli, P, Borgwardt, S, Bechdolf, A, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013; 70(1): 107120.
26.Üçok, A, Ergül, C. Persistent negative symptoms after first episode schizophrenia: a 2-year follow-up study. Schizophr Res. 2014; 158(1–3): 241246.
27.Thorup, A, Albert, N, Bertelsen, M, et al. Gender differences in first-episode psychosis at 5-year follow-up-two different courses of disease? Results from the OPUS study at 5-year follow-up. Eur Psychiatry. 2014; 29(1): 4451.
28.Nordon, C, Rouillon, F, Azorin, JM, Barry, C, Urbach, M, Falissard, B. Trajectories of antipsychotic response in drug-naive schizophrenia patients: results from the 6-month ESPASS follow-up study. Acta Psychiatr Scand. 2014; 129(2): 116125.
29.Gaebel, W, Riesbeck, M, Wölwer, W, et al. Rates and predictors of remission in first-episode schizophrenia within 1 year of antipsychotic maintenance treatment: results of a randomized controlled trial within the German Research Network on Schizophrenia. Schizophr Res. 2014; 152(2–3): 478486.
30.Fervaha, G, Foussias, G, Agid, O, Remington, G. Impact of primary negative symptoms on functional outcomes in schizophrenia. Eur Psychiatry. 2014; 29(7): 449455.
31.Verma, S, Subramaniam, M, Abdin, E, Poon, LY, Chong, SA. Symptomatic and functional remission in patients with first-episode psychosis. Acta Psychiatr Scand. 2012; 126(4): 282289.
32.Carbon, M, Correll, CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. In press.
33.Bilder, RM, Goldman, RS, Robinson, D, et al. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry. 2000; 157(4): 549559.
34.Gold, JM, Weinberger, DR. Cognitive deficits and the neurobiology of schizophrenia. Curr Opin Neurobiol. 1995; 5(2): 225230.
35.Javitt, DC, Doneshka, P, Grochowski, S, Ritter, W. Impaired mismatch negativity generation reflects widespread dysfunction of working memory in schizophrenia. Arch Gen Psychiatry. 1995; 52(7): 550558.
36.Green, MF, Nuechterlein, KH, Gold, JM, et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry. 2004; 56(5): 301307.
37.Fusar-Poli, P, Deste, G, Smieskova, R, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012; 69(6): 562571.
38.Brewer, WJ, Wood, SJ, Phillips, LJ, et al. Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. Schizophr Bull. 2006; 32(3): 538555.
39.Bora, E, Lin, A, Wood, SJ, Yung, AR, McGorry, PD, Pantelis, C. Cognitive deficits in youth with familial and clinical high risk to psychosis: a systematic review and meta-analysis. Acta Psychiatr Scand. 2014; 130(1): 115.
40.Olvet, DM, Burdick, KE, Cornblatt, BA. Assessing the potential to use neurocognition to predict who is at risk for developing bipolar disorder: a review of the literature. Cogn Neuropsychiatry. 2013; 18(1–2): 129145.
41.Galderisi, S, Davidson, M, Kahn, RS, et al; EUFEST group. Correlates of cognitive impairment in first episode schizophrenia: the EUFEST study. Schizophr Res. 2009; 115(2–3): 104114.
42.Fatouros-Bergman, H, Cervenka, S, Flyckt, L, Edman, G, Farde, L. Meta-analysis of cognitive performance in drug-naïve patients with schizophrenia. Schizophr Res. 2014; 158(1–3): 156162.
43.Bora, E, Murray, RM. Meta-analysis of cognitive deficits in ultra-high risk to psychosis and first-episode psychosis: do the cognitive deficits progress over, or after, the onset of psychosis? Schizophr Bull. 2014; 40(4): 744755.
44.Andreasen, NC, Rezai, K, Alliger, R, et al. Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia: assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry. 1992; 49(12): 943958.
45.Bozikas, VP, Kosmidis, MH, Kioperlidou, K, Karavatos, A. Relationship between psychopathology and cognitive functioning in schizophrenia. Compr Psychiatry. 2004; 45(5): 392400.
46.Buchanan, RW, Strauss, ME, Breier, A, Kirkpatrick, B, Carpenter, WT Jr. Attentional impairments in deficit and nondeficit forms of schizophrenia. Am J Psychiatry. 1997; 154(3): 363370.
47.Hughes, C, Kumari, V, Soni, W, et al. Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Schizophr Res. 2003; 59(2–3): 137146.
48.Keefe, RS, Bilder, RM, Harvey, PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology. 2006; 31(9): 20332046.
49.Sponheim, SR, Jung, RE, Seidman, LJ, et al. Cognitive deficits in recent-onset and chronic schizophrenia. J Psychiatr Res. 2010; 44(7): 421428.
50.Bozikas, VP, Andreou, C. Longitudinal studies of cognition in first episode psychosis: a systematic review of the literature. Aust N Z J Psychiatry. 2011; 45(2): 93108.
51. Barder, HE, Sundet, K, Rund, BR, et al. Ten year neurocognitive trajectories in first-episode psychosis. Front Hum Neurosci. 2013; 7: 643.
52.Mesholam-Gately, RI, Giuliano, AJ, Goff, KP, Faraone, SV, Seidman, LJ. Neurocognition in first-episode schizophrenia: a meta-analytic review. Neuropsychology. 2009; 23(3): 315336.
53.Sitskoorn, MM, Aleman, A, Ebisch, SJ, Appels, MC, Kahn, RS. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res. 2004; 71(2–3): 285295.
54.Dickerson, F, Boronow, JJ, Stallings, C, Origoni, AE, Cole, SK, Yolken, RH. Cognitive functioning in schizophrenia and bipolar disorder: comparison of performance on the Repeatable Battery for the Assessment of Neuropsychological Status. Psychiatry Res. 2004; 129(1): 4553.
55.Krabbendam, L, Arts, B, Van Os, J, Aleman, A. Cognitive functioning in patients with schizophrenia and bipolar disorder: a quantitative review. Schizophr Res. 2005; 80(2–3): 137149.
56.Bora, E, Yucel, M, Pantelis, C. Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. Br J Psychiatry. 2009; 195(6): 475482.
57.Pantelis, C, Stuart, GW, Nelson, HE, Robbins, TW, Barnes, TRE. Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms. Am J Psychiatry. 2001; 158(8): 12761285.
58.Keefe, RS. Should cognitive impairment be included in the diagnostic criteria for schizophrenia? World Psychiatry. 2008; 7(1): 2228.
59.Brandt, J, Benedict, R. Hopkins Verbal Learning Test. Lutz, FL: Psychological Assessment Resources; 1991.
60.Randolph, C, Tierney, MC, Mohr, E, Chase, TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998; 20(3): 310319.
61.Loughland, CM, Lewin, TJ, Carr, VJ, Sheedy, J, Harris, AW. RBANS neuropsychological profiles within schizophrenia samples recruited from non-clinical settings. Schizophr Res. 2007; 89(1–3): 232242.
62.Chianetta, JM, Lefebvre, M, LeBlanc, R, Grignon, S. Comparative psychometric properties of the BACS and RBANS in patients with schizophrenia and schizoaffective disorder. Schizophr Res. 2008; 105(1–3): 8694.
63.Ehrenreich, H, Hinze-Selch, D, Stawicki, S, et al. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry. 2007; 12(2): 206220.
64.Fenton, WS, Dickerson, F, Boronow, JJ, Hibbeln, JR, Knable, M. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001; 158(12): 20712074.
65.Olincy, A, Harris, JG, Johnson, LL, et al. Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry. 2006; 63(6): 630638.
66.Nuechterlein, KH, Barch, DM, Gold, JM, Goldberg, TE, Green, MF, Heaton, RK. Identification of separable cognitive factors in schizophrenia. Schizophr Res. 2004; 72(1): 2939.
67.Pantelis, C, Barnes, TR, Nelson, HE, et al. Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain. 1997; 120(Pt 10): 18231843.
68.Keefe, RS, Goldberg, TE, Harvey, PD, Gold, JM, Poe, MP, Coughenour, L. The Brief Assessment of Cognition in Schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res. 2004; 68(2–3): 283297.
69.Caletti, E, Paoli, RA, Fiorentini, A, et al. Neuropsychology, social cognition and global functioning among bipolar, schizophrenic patients and healthy controls: preliminary data. Front Hum Neurosci. 2013; 7: 661.
70.Kaneda, A, Katagai, T, Yasui-Furukori, N. Comparing the influences of age and disease on the Brief Assessment of Cognition in Schizophrenia in Japanese patients with schizophrenia. Neuropsychiatr Dis Treat. 2013; 9: 12031208.
71.Hill, SK, Reilly, JL, Keefe, RS, et al. Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Am J Psychiatry. 2013; 170(11): 12751284.
72.Hill, SK, Sweeney, JA, Hamer, RM, et al. Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia. J Int Neuropsychol Soc. 2008; 14(2): 209221.
73.Sellwood, W, Morrison, AP, Beck, R, Heffernan, S, Law, H, Bentall, RP. Subjective cognitive complaints in schizophrenia: relation to antipsychotic medication dose, actual cognitive performance, insight and symptoms. PLoS One. 2013; 8(12): e83774.
74.Suzuki, H, Gen, K, Inoue, Y, et al. The influence of switching from risperidone to paliperidone on the extrapyramidal symptoms and cognitive function in elderly patients with schizophrenia: a preliminary open-label trial. Int J Psychiatry Clin Pract. 2014; 18(1): 5862.
75.Wang, HL, Xiang, YT, Li, QY, et al. The effect of artemether on psychotic symptoms and cognitive impairment in first-episode, antipsychotic drug-naive persons with schizophrenia seropositive to Toxoplasma gondii. J Psychiatr Res. 2014; 53: 119124.
76.Buchanan, RW, Davis, M, Goff, D, et al. A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull. 2005; 31(1): 519.
77.Buchanan, RW, Keefe, RS, Umbricht, D, Green, MF, Laughren, T, Marder, SR. The FDA-NIMH-MATRICS guidelines for clinical trial design of cognitive-enhancing drugs: what do we know 5 years later? Schizophr Bull. 2011; 37(6): 12091217.
78.Nuechterlein, KH, Green, MF, Kern, RS, et al. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008; 165(2): 203213.
79.Kern, RS, Gold, JM, Dickinson, D, et al. The MCCB impairment profile for schizophrenia outpatients: results from the MATRICS psychometric and standardization study. Schizophr Res. 2011; 126(1–3): 124131.
80.Keefe, RS, Fox, KH, Harvey, PD, Cucchiaro, J, Siu, C, Loebel, A. Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site antipsychotic schizophrenia clinical trial. Schizophr Res. 2011; 125(2–3): 161168.
81.Jarskog, LF, Dong, Z, Kangarlu, A, et al. Effects of davunetide on N-acetylaspartate and choline in dorsolateral prefrontal cortex in patients with schizophrenia. Neuropsychopharmacology. 2013; 38(7): 12451252.
82.Weiser, M, Heresco-Levy, J, Davidson, M, Javitt, DC, Werbeloff, N, Gershon, AA, Abramovich, Y, Amital, D, Doron, A, Konas, S, Levkovitz, Y, Liba, D, Teitelbaum, A, Mashiach, M, Zimmerman, Y. A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry. 2012; 73: e72834.
83.Keefe, RS, Poe, M, Walker, TM, Kang, JW, Harvey, PD. The Schizophrenia Cognition Rating Scale: an interview-based assessment and its relationship to cognition, real-world functioning, and functional capacity. Am J Psychiatry. 2006; 163(3): 426432.
84.Poletti, S, Anselmetti, S, Riccaboni, R, et al. Self-awareness of cognitive functioning in schizophrenia: patients and their relatives. Psychiatry Res. 2012; 198(2): 207211.
85.Vita, A, Deste, G, Barlati, S, et al. Interview-based assessment of cognition in schizophrenia: applicability of the Schizophrenia Cognition Rating Scale (SCoRS) in different phases of illness and settings of care. Schizophr Res. 2013; 146(1–3): 217223.
86.Harvey, PD, Ogasa, M, Cucchiaro, J, Loebel, A, Keefe, RS. Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone. Schizophr Res. 2011; 127(1–3): 188194.
87.Bora, E, Yücel, M, Pantelis, C. Cognitive impairment in schizophrenia and affective psychoses: implications for DSM-V criteria and beyond. Schizophr Bull. 2010; 36(1): 3642.
88.Palmer, BW, Heaton, RK, Paulsen, JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology. 1997; 11(3): 437446.
89.Keefe, RSE, Eesley, CE, Poe, M. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry. 2005; 57(6): 688691.
90.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996; 153(3): 321330.
91.Evans, JD, Heaton, RK, Paulsen, JS, Palmer, BW, Patterson, T, Jeste, DV. The relationship of neuropsychological abilities to specific domains of functional capacity in older schizophrenic patients. Biol Psychiatry. 2003; 53(5): 422430.
92.Gold, S, Arndt, S, Nopoulos, P, O’Leary, DS, Andreasen, NC. Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia. Am J Psychiatry. 1999; 156(9): 13421348.
93.Jordan, G, Lutgens, D, Joober, R, Lepage, M, Iyer, S, Malla, A. The relative contribution of cognition and symptomatic remission to functional outcome following treatment of a first episode of psychosis. J Clin Psychiatry. 2014; 75(6): e566e572.
94.Milev, P, Ho, BC, Arndt, S, Andreasen, NC. 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. 2005; 162(3): 495506.
95.Stirling, J, White, C, Lewis, S, et al. Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up of an epidemiological cohort. Schizophr Res. 2003; 65(2–3): 7586.
96.Rajji, TK, Miranda, D, Mulsant, BH. Cognition, function, and disability in patients with schizophrenia: a review of longitudinal studies. Can J Psychiatry. 2014; 59(1): 1317.
97.Allott, K, Liu, P, Proffitt, TM, Killackey, E. Cognition at illness onset as a predictor of later functional outcome in early psychosis: systematic review and methodological critique. Schizophr Res. 2011; 125(2–3): 221235.
98.Ventura, J, Cienfuegos, A, Boxer, O, Bilder, R. Clinical Global Impression of Cognition in Schizophrenia (CGI-CogS): reliability and validity of a co-primary measure of cognition. Schizophr Res. 2008; 106(1): 5969.
99.Ventura, J, Reise, SP, Keefe, RS, et al. The Cognitive Assessment Interview (CAI): development and validation of an empirically derived, brief interview-based measure of cognition. Schizophr Res. 2010; 121(1–3): 2431.
100.Bowie, CR, Reichenberg, A, Patterson, TL, Heaton, RK, Harvey, PD. Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms. Am J Psychiatry. 2006; 163(3): 418425.
101.Fervaha, G, Zakzanis, KK, Foussias, G, Graff-Guerrero, A, Agid, O, Remington, G. Motivational deficits and cognitive test performance in schizophrenia. JAMA Psychiatry. 2014; 71(9): 10581065.
102.Fervaha, G, Foussias, G, Agid, O, Remington, G. Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia. Acta Psychiatr Scand. 2014; 130(4): 290299.
103.Schmidt, SJ, Mueller, DR, Roder, V. Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modeling. Schizophr Bull. 2011; 37(Suppl 2): S41S54.
104.Nakagami, E, Xie, B, Hoe, M, Brekke, JS. Intrinsic motivation, neurocognition and psychosocial functioning in schizophrenia: testing mediator and moderator effects. Schizophr Res. 2008; 105(1–3): 95104.
105.Keshavan, MS, Vinogradov, S, Rumsey, J, Sherrill, J, Wagner, A. Cognitive training in mental disorders: update and future directions. Am J Psychiatry. 2014; 171(5): 510522.
106.Grant, PM, Huh, GA, Perivoliotis, D, Stolar, NM, Beck, AT. Randomized trial to evaluate the efficacy of cognitive therapy for low-functioning patients with schizophrenia. Arch Gen Psychiatry. 2012; 69(2): 121127.
107.Jauhar, S, McKenna, PJ, Radua, J, Fung, E, Salvador, R, Laws, KR. Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias. Br J Psychiatry. 2014; 204(1): 2029.
108.Dixon, LB, Dickerson, F, Bellack, AS, et al. Schizophrenia Patient Outcomes Research Team (PORT). The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010; 36(1): 4870.
109.Wykes, T, Steel, C, Everitt, B, Tarrier, N. Cognitive behavior therapy for schizophrenia: effect sizes, clinical models, and methodological rigor. Schizophr Bull. 2008; 34(3): 523537.
110.Elis, O, Caponigro, JM, Kring, AM. Psychosocial treatments for negative symptoms in schizophrenia: current practices and future directions. Clin Psychol Rev. 2013; 33(8): 914928.
111.Klingberg, S, Wölwer, W, Engel, C, et al. Negative symptoms of schizophrenia as primary target of cognitive behavioral therapy: results of the randomized clinical TONES study. Schizophr Bull. 2011; 37(Suppl 2): S98110.
112.Medalia, A, Saperstein, AM. Does cognitive remediation for schizophrenia improve functional outcomes? Curr Opin Psychiatry. 2013; 26(2): 151157.
113.Wykes, T, Huddy, V, Cellard, C, McGurk, SR, Czobor, P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011; 168(5): 472485.
114.Puig, O, Penadés, R, Baeza, I, et al. Cognitive remediation therapy in adolescents with early-onset schizophrenia: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2014; 53(8): 859868.
115.Trapp, W, Landgrebe, M, Hoesl, K, et al. Cognitive remediation improves cognition and good cognitive performance increases time to relapse—results of a 5 year catamnestic study in schizophrenia patients. BMC Psychiatry. 2013; 13: 184.
116.Liberman, RP, Wallace, CJ, Blackwell, G, Kopelowicz, A, Vaccaro, JV, Mintz, J. Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia. Am J Psychiatry. 1998; 155(8): 10871091.
117.Rus-Calafell, M, Gutiérrez-Maldonado, J, Ortega-Bravo, M, Ribas-Sabaté, J, Caqueo-Urízar, A. A brief cognitive-behavioural social skills training for stabilised outpatients with schizophrenia: a preliminary study. Schizophr Res. 2013; 143(2–3): 327336.
118.Nordentoft, M, Melau, M, Iversen, T, et al. From research to practice: how OPUS treatment was accepted and implemented throughout Denmark. Early Interv Psychiatry. In press. DOI: 10.1111/eip.12108.
119.Dickinson, D, Tenhula, W, Morris, S, et al. A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia. Am J Psychiatry. 2010; 167(2): 170180.
120.Grynszpan, O, Perbal, S, Pelissolo, A, et al. Efficacy and specificity of computer-assisted cognitive remediation in schizophrenia: a meta-analytical study. Psychol Med. 2011; 41(1): 163173.
121.Millan, MJ, Fone, K, Steckler, T, Horan, WP. Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014; 24(5): 645692.
122.Leucht, S, Komossa, K, Rummel-Kluge, C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009; 166(2): 152163.
123.Fervaha, G, Foussias, G, Agid, O, Remington, G. Neural substrates underlying effort computation in schizophrenia. Neurosci Biobehav Rev. 2013; 37(10 Pt 2): 26492665.
124.Padmanabhan, JL, Tandon, N, Haller, CS, et al. Correlations between brain structure and symptom dimensions of psychosis in schizophrenia, schizoaffective, and psychotic bipolar I disorders. Schizophr Bull. In press. DOI: 10.1093/schbul/sbu075.
125.Millan, MJ, Fone, K, Steckler, T, Horan, WP. Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. Eur Neuropsychopharmacol. 2014; 24(5): 645692.
126.Köster, LS, Carbon, M, Correll, CU. Emerging drugs for schizophrenia: an update. Expert Opin Emerg Drugs. 2014; 19: 121. [Epub ahead of print] PMID: 25234340.
127.Duncan, GE, Zorn, S, Lieberman, JA. Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia. Mol Psychiatry. 1999; 4(5): 418428.
128.Millan, MJ. N-Methyl-D-aspartate receptors as a target for improved antipsychotic agents: novel insights and clinical perspectives. Psychopharmacology (Berl). 2005; 179(1): 3053.
129.Leucht, S, Pitschel-Walz, G, Engel, RR, Kissling, W. Amisulpride, an unusual “atypical” antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry. 2002; 159(2): 180190.
130.McEvoy, JP, Lieberman, JA, Stroup, TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006; 163(4): 600610.
131.Stroup, TS, Lieberman, JA, McEvoy, JP, et al. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry. 2006; 163(4): 611622.
132.Souza, JS, Kayo, M, Tassell, I, Martins, CB, Elkis, H. Efficacy of olanzapine in comparison with clozapine for treatment-resistant schizophrenia: evidence from a systematic review and meta-analyses. CNS Spectr. 2013; 18(2): 8289.
133.Leucht, S, Komossa, K, Rummel-Kluge, C, et al. A meta-analysis of head-to-head comparisons of second-generation antipsychotics in the treatment of schizophrenia. Am J Psychiatry. 2009; 166(2): 152163.
134.Kern, RS, Green, MF, Cornblatt, BA, et al. The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology (Berl). 2006; 187(3): 312320.
135.Harvey, PD, Ogasa, M, Cucchiaro, J, Loebel, A, Keefe, RS. Performance and interview-based assessments of cognitive change in a randomized, double-blind comparison of lurasidone vs. ziprasidone. Schizophr Res. 2011; 127(1–3): 188194.
136.Keefe, RS, Bilder, RM, Davis, SM, et al; CATIE Investigators; Neurocognitive Working Group. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry. 2007; 64(6): 633647.
137.Rummel, C, Kissling, W, Leucht, S. Antidepressants for the negative symptoms of schizophrenia. Cochrane Database Syst Rev. 2006; (3): CD005581.
138.Sepehry, AA, Potvin, S, Elie, R, et al. Selective serotonin reuptake inhibitor (SSRI) add-on therapy for the negative symptoms of schizophrenia: a meta-analysis. J Clin Psychiatry. 2007; 68(4): 604610.
139.Singh, SP, Singh, V, Kar, N, et al. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry. 2010; 197(3): 174179.
140.Kishi, T, Meltzer, HY, Iwata, N. Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists: a meta-analysis. Int J Neuropsychopharmacol. 2013; 16(6): 12591266.
141.Sumiyoshi, T, Park, S, Jayathilake, K, Roy, A, Ertugrul, A, Meltzer, HY. Effect of buspirone, a serotonin1A partial agonist, on cognitive function in schizophrenia: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2007; 95(1–3): 158168.
142.Sumiyoshi, T, Matsui, M, Yamashita, I, et al. The effect of tandospirone, a serotonin(1A) agonist, on memory function in schizophrenia. Biol Psychiatry. 2001; 49(10): 861868.
143.Akhondzadeh, S, Mohammadi, N, Noroozian, M, et al. Added ondansetron for stable schizophrenia: a double blind, placebo controlled trial. Schizophr Res. 2009; 107(2–3): 206212.
144.Zhang, XY, Liu, L, Liu, S, et al. Short-term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia. Am J Psychiatry. 2012; 169(9): 974981.
145.Morozova, MA, Beniashvili, AG, Lepilkina, TA, Rupchev, GE. Double-blind placebo-controlled randomized efficacy and safety trial of add-on treatment of dimebon plus risperidone in schizophrenic patients during transition from acute psychotic episode to remission. Psychiatr Danub. 2012; 24(2): 159166.
146.Vernon, JA, Grudnikoff, E, Seidman, AJ, et al. Antidepressants for cognitive symptoms in schizophrenia—a systematic review and meta-analysis. Schizophr Res. In press. doi;10.1016/j.schres.2014.08.015.
147.Tuominen, HJ, Tiihonen, J, Wahlbeck, K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev. 2006; (2): CD003730. Review. PubMed PMID:16625590.
148.Buchanan, RW, Javitt, DC, Marder, SR, et al. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry. 2007; 164(10): 15931602.
149.Goff, DC, Cather, C, Gottlieb, JD, et al. Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study. Schizophr Res. 2008; 106(2–3): 320327.
150.Patil, ST, Zhang, L, Martenyi, F, et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med. 2007; 13(9): 11021107.
151.Stauffer, VL, Millen, BA, Andersen, S, et al. Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo. Schizophr Res. 2013; 150(2–3): 434441.
152.Addex Web Page. Press release: Addex reports top-line data from a successful phase 2a clinical study with ADX71149 in schizophrenia patients. November 5, 2012.
153.Lavoie, S, Murray, MM, Deppen, P, et al. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology. 2008; 33(9): 21872199.
154.Kantrowitz, JT, Malhotra, AK, Cornblatt, B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010; 121(1–3): 125130.
155.Lane, HY, Chang, YC, Liu, YC, et al. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. 2005; 62(11): 11961204.
156.Pinard, E, Alanine, A, Alberati, D, et al. Selective GlyT1 inhibitors: discovery of [4-(3-fluoro-5-trifluoromethylpyridin-2-yl) piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia. J Med Chem. 2010; 53(12): 46034614.
157.Umbricht, D, Alberati, D, Martin-Facklam, M, et al. Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study. JAMA Psychiatry. 2014; 71(6): 637646.
158.Ferraris, DV, Tsukamoto, T. Recent advances in the discovery of D-amino acid oxidase inhibitors and their therapeutic utility in schizophrenia. Curr Pharm Des. 2011; 17(2): 103111.
159.Lane, HY, Lin, CH, Green, MF, et al. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013; 70(12): 12671275.
160.Hashimoto, K, Malchow, B, Falkai, P, Schmitt, A. Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Eur Arch Psychiatry Clin Neurosci. 2013; 263(5): 367377.
161.Jones, CK, Byun, N, Bubser, M. Muscarinic and nicotinic acetylcholine receptor agonists and allosteric modulators for the treatment of schizophrenia. Neuropsychopharmacology. 2012; 37(1): 1642.
162.Shekhar, A, Potter, WZ, Lightfoot, J, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008; 165(8): 10331039.
163.Lee, BJ, Lee, JG, Kim, YH. A 12-week, double-blind, placebo-controlled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia. J Psychopharmacol. 2007; 21(4): 421427.
164.Lee, SW, Lee, JG, Lee, BJ, Kim, YH. 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. 2007; 22(2): 6368.
165.Schubert, MH, Young, KA, Hicks, PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry. 2006; 60(6): 530533.
166.Stip, E, Sepehry, AA, Chouinard, S. Add-on therapy with acetylcholinesterase inhibitors for memory dysfunction in schizophrenia: a systematic quantitative review, part 2. Clin Neuropharmacol. 2007; 30(4): 218229.
167.Chouinard, S, Sepehry, AA, Stip, E. Oral cholinesterase inhibitor add-on therapy for cognitive enhancement in schizophrenia: a quantitative systematic review, part I. Clin Neuropharmacol. 2007; 30(3): 169182.
168.Strous, RD, Maayan, R, Lapidus, R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry. 2003; 60(2): 133141.
169.Strous, RD, Stryjer, R, Maayan, R, et al. Analysis of clinical symptomatology, extrapyramidal symptoms and neurocognitive dysfunction following dehydroepiandrosterone (DHEA) administration in olanzapine treated schizophrenia patients: a randomized, double-blind placebo controlled trial. Psychoneuroendocrinology. 2007; 32(2): 96105.
170.Ko, YH, Lew, YM, Jung, SW, et al. Short-term testosterone augmentation in male schizophrenics: a randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2008; 28(4): 375383.
171.Ritsner, MS, Gibel, A, Ratner, Y, Tsinovoy, G, Strous, RD. Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychopharmacol. 2006; 26(5): 495499.
172.Begemann, MJ, Dekker, CF, van Lunenburg, M, Sommer, IE. Estrogen augmentation in schizophrenia: a quantitative review of current evidence. Schizophr Res. 2012; 141(2–3): 179184.
173.Ritsner, MS, Gibel, A, Shleifer, T, et al. Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomized, controlled, 2-center, parallel-group trial. J Clin Psychiatry. 2010; 71(10): 13511362.
174.Barch, DM, Carter, CS. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res. 2005; 77(1): 4358.
175.Lindenmayer, JP, Nasrallah, H, Pucci, M, James, S, Citrome, L. A systematic review of psychostimulant treatment of negative symptoms of schizophrenia: challenges and therapeutic opportunities. Schizophr Res. 2013; 147(2–3): 241252.
176.Lasser, RA, Dirks, B, Nasrallah, H, et al. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases. Neuropsychopharmacology. 2013; 38(11): 21402149.
177.Bobo, WV, Woodward, ND, Sim, MY, Jayathilake, K, Meltzer, HY. The effect of adjunctive armodafinil on cognitive performance and psychopathology in antipsychotic-treated patients with schizophrenia/schizoaffective disorder: a randomized, double-blind, placebo-controlled trial. Schizophr Res. 2011; 130(1–3): 106113.
178.Kane, JM, Yang, R, Youakim, JM. Adjunctive armodafinil for negative symptoms in adults with schizophrenia: a double-blind, placebo-controlled study. Schizophr Res. 2012; 135(1–3): 116122.
179.Lohr, JB, Liu, L, Caligiuri, MP, et al. Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study. Schizophr Res. 2013; 150(1): 289296.
180.Lefaucheur, JP, André-Obadia, N, Antal, A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. In press. DOI: 10.1016/j.clinph.2014.05.021.
181.Shi, C, Yu, X, Cheung, EF, Shum, DH, Chan, RC. Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: a meta-analysis. Psychiatry Res. 2014; 215(3): 505513.
182.Liu, F, Guo, X, Wu, R, et al. Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: a double blind, randomized, controlled trial. Schizophr Res. 2014; 153(1–3): 169176.
183.Berk, M, Copolov, D, Dean, O, et al. N-Acetyl cysteine as a glutathione precursor for schizophrenia—a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008; 64(5): 361368.
184.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2): 261276.
185.Marder, SR, Davis, JM, Chouinard, G. The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials. J Clin Psychiatry. 1997; 58(12): 538546.
186.Andreasen, NC. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry Suppl. 1989; 7: 4958.
187.Axelrod, BN, Goldman, RS, Alphs, LD. Validation of the 16-item Negative Symptom Assessment. J Psychiatr Res. 1993; 27(3): 253258.
188.Pietrzak, RH, Olver, J, Norman, T, Piskulic, D, Maruff, P, Snyder, PJ. A comparison of the CogState Schizophrenia Battery and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery in assessing cognitive impairment in chronic schizophrenia. J Clin Exp Neuropsychol. 2009; 31(7): 848859.
189.Wilk, CM, Gold, JM, Bartko, JJ, et al. Test-retest stability of the Repeatable Battery for the Assessment of Neuropsychological Status in schizophrenia. Am J Psychiatry. 2002; 159(5): 838844.
190.Hurford, IM, Marder, SR, Keefe, RS, Reise, SP, Bilder, RM. A brief cognitive assessment tool for schizophrenia: construction of a tool for clinicians. Schizophr Bull. 2011; 37(3): 538545.
191.Dickinson, D, Ramsey, ME, Gold, JM. Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Arch Gen Psychiatry. 2007; 64(5): 532542.
192.Wu, C, Dagg, P, Molgat, C. A pilot study to measure cognitive impairment in patients with severe schizophrenia with the Montreal Cognitive Assessment (MoCA). Schizophr Res. 2014; 158(1–3): 151155.
193.Nasreddine, Z. The Montreal Cognitive Assessment.
194.Gioia, GA, Isquith, PK, Guy, SC, Kenworthy, L. Behavior rating inventory of executive function. Child Neuropsychol. 2000; 6(3): 235238.
195.Opler, M, Antonius, D, Correll, CU. New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT). Unpublished rating instrument.
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CNS Spectrums
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