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

Published online by Cambridge University Press:  18 November 2014

Maren Carbon  and
Christoph U. Correll
Maren Carbon
Affiliation:
Psychiatry Research, The Zucker Hillside Hospital, North Shore—Long Island Jewish Health System, Glen Oaks, New York, USA
Christoph U. Correll*
Affiliation:
Psychiatry Research, The Zucker Hillside Hospital, North Shore—Long Island Jewish Health System, Glen Oaks, New York, USA Psychiatry and Molecular Medinine, Hofstra North Shore LIJ School of Medicine, Hempstead, New York, USA Psychiatric Neuroscience Center of Excellence, The Feinstein Institute for Medical Research, Manhasset, New York, USA Psychiatry, Albert Einstein College of Medicine, Bronx, New York, USA
*
*Address for correspondence: Christoph U. Correll, MD, The Zucker Hillside Hospital, Psychiatry, 75-59 263rd Street, Glen Oaks, NY 11004, USA. (Email: ccorrell@lij.edu)
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Abstract

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.

Keywords

Assessmentcognitionnegative symptomsschizophreniatreatment
Type
CME Review Article
Information
CNS Spectrums , Volume 19 , Issue S1: CME SUPPLEMENT , December 2014 , pp. 35 - 53
Copyright
© Cambridge University Press 2014 

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Footnotes

This activity is supported by an educational grant from Envivo Pharmaceuticals, LLC (a.k.a. FORUM Pharmaceuticals, Inc)

References

1.Kirkpatrick, B, Strauss, GP, Nguyen, L, et al. The brief negative symptom scale: psychometric properties. Schizophr Bull. 2011; 37(2): 300–305.Google Scholar
2.Blanchard, JJ, Cohen, AS. The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr Bull. 2006; 32(2): 238–245.Google Scholar
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): 165–172.Google Scholar
4.Foussias, G, Remington, G. Negative symptoms in schizophrenia: avolition and Occam's razor. Schizophr Bull. 2010; 36(2): 359–369.Google Scholar
5.Pizzagalli, DA. The “anhedonia paradox” in schizophrenia: insights from affective neuroscience. Biol Psychiatry. 2010; 67(10): 899–901.Google Scholar
6.Cohen, AS, Minor, KS. Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophr Bull. 2010; 36(1): 143–150.CrossRefGoogle ScholarPubMed
7.Buchanan, RW. Persistent negative symptoms in schizophrenia: an overview. Schizophr Bull. 2007; 33(4): 1013–1022.CrossRefGoogle ScholarPubMed
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): 453–461.Google Scholar
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): 339–342.Google Scholar
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): 125–127.Google Scholar
11.Galderisi, S, Maj, M. Deficit schizophrenia: an overview of clinical, biological and treatment aspects. Eur Psychiatry. 2009; 24(8): 493–500.Google Scholar
12.Correll, CU, Kishimoto, T, Nielsen, J, Kane, JM. Quantifying clinical relevance in the treatment of schizophrenia. Clin Ther. 2011; 33(12): B16–B39.Google Scholar
13.Kane, JM. Tools to assess negative symptoms in schizophrenia. J Clin Psychiatry. 2013; 74(6): e12.Google Scholar
14.Selten, JP, Wiersma, D, van den Bosch, RJ. Discrepancy between subjective and objective ratings for negative symptoms. J Psychiatr Res. 2000; 34(1): 11–13.CrossRefGoogle ScholarPubMed
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): 328–333.Google Scholar
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): 159–163.Google Scholar
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): e31–e37.Google Scholar
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): 36–42.CrossRefGoogle ScholarPubMed
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): 88–92.Google Scholar
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): 280–286.Google Scholar
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): 783–790.Google Scholar
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): 13–26.CrossRefGoogle ScholarPubMed
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): 128–133.Google Scholar
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): 125–131.Google Scholar
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): 107–120.Google Scholar
26.Üçok, A, Ergül, C. Persistent negative symptoms after first episode schizophrenia: a 2-year follow-up study. Schizophr Res. 2014; 158(1–3): 241–246.Google Scholar
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): 44–51.Google Scholar
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): 116–125.CrossRefGoogle ScholarPubMed
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): 478–486.Google Scholar
30.Fervaha, G, Foussias, G, Agid, O, Remington, G. Impact of primary negative symptoms on functional outcomes in schizophrenia. Eur Psychiatry. 2014; 29(7): 449–455.Google Scholar
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): 282–289.CrossRefGoogle ScholarPubMed
32.Carbon, M, Correll, CU. Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. In press.Google Scholar
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): 549–559.CrossRefGoogle ScholarPubMed
34.Gold, JM, Weinberger, DR. Cognitive deficits and the neurobiology of schizophrenia. Curr Opin Neurobiol. 1995; 5(2): 225–230.Google Scholar
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): 550–558.CrossRefGoogle ScholarPubMed
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): 301–307.Google Scholar
37.Fusar-Poli, P, Deste, G, Smieskova, R, et al. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry. 2012; 69(6): 562–571.Google Scholar
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): 538–555.Google Scholar
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): 1–15.Google Scholar
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): 129–145.Google Scholar
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): 104–114.Google Scholar
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): 156–162.Google Scholar
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): 744–755.Google Scholar
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): 943–958.Google Scholar
45.Bozikas, VP, Kosmidis, MH, Kioperlidou, K, Karavatos, A. Relationship between psychopathology and cognitive functioning in schizophrenia. Compr Psychiatry. 2004; 45(5): 392–400.Google Scholar
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): 363–370.Google ScholarPubMed
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): 137–146.Google Scholar
48.Keefe, RS, Bilder, RM, Harvey, PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology. 2006; 31(9): 2033–2046.CrossRefGoogle ScholarPubMed
49.Sponheim, SR, Jung, RE, Seidman, LJ, et al. Cognitive deficits in recent-onset and chronic schizophrenia. J Psychiatr Res. 2010; 44(7): 421–428.Google Scholar
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): 93–108.Google Scholar
51. Barder, HE, Sundet, K, Rund, BR, et al. Ten year neurocognitive trajectories in first-episode psychosis. Front Hum Neurosci. 2013; 7: 643.Google Scholar
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): 315–336.Google Scholar
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): 285–295.CrossRefGoogle ScholarPubMed
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): 45–53.Google Scholar
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): 137–149.Google Scholar
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): 475–482.Google Scholar
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): 1276–1285.Google Scholar
58.Keefe, RS. Should cognitive impairment be included in the diagnostic criteria for schizophrenia? World Psychiatry. 2008; 7(1): 22–28.Google Scholar
59.Brandt, J, Benedict, R. Hopkins Verbal Learning Test. Lutz, FL: Psychological Assessment Resources; 1991.Google Scholar
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): 310–319.Google Scholar
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): 232–242.Google Scholar
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): 86–94.Google Scholar
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): 206–220.Google Scholar
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): 2071–2074.Google Scholar
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): 630–638.Google Scholar
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): 29–39.Google Scholar
67.Pantelis, C, Barnes, TR, Nelson, HE, et al. Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain. 1997; 120(Pt 10): 1823–1843.Google Scholar
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): 283–297.Google Scholar
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.Google Scholar
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: 1203–1208.Google Scholar
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): 1275–1284.Google Scholar
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): 209–221.Google Scholar
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.Google Scholar
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): 58–62.Google Scholar
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: 119–124.Google Scholar
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): 5–19.CrossRefGoogle ScholarPubMed
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): 1209–1217.Google Scholar
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): 203–213.Google Scholar
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): 124–131.Google Scholar
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): 161–168.Google Scholar
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): 1245–1252.Google Scholar
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: e728–34.Google Scholar
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): 426–432.Google Scholar
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): 207–211.Google Scholar
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): 217–223.Google Scholar
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): 188–194.Google Scholar
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): 36–42.Google Scholar
88.Palmer, BW, Heaton, RK, Paulsen, JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology. 1997; 11(3): 437–446.Google Scholar
89.Keefe, RSE, Eesley, CE, Poe, M. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry. 2005; 57(6): 688–691.Google Scholar
90.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996; 153(3): 321–330.Google Scholar
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): 422–430.Google Scholar
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): 1342–1348.Google Scholar
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): e566–e572.Google Scholar
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): 495–506.Google Scholar
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): 75–86.Google Scholar
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): 13–17.Google Scholar
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): 221–235.Google Scholar
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): 59–69.Google Scholar
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): 24–31.Google Scholar
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): 418–425.Google Scholar
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): 1058–1065.Google Scholar
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): 290–299.Google Scholar
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): S41–S54.Google Scholar
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): 95–104.Google Scholar
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): 510–522.CrossRefGoogle ScholarPubMed
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): 121–127.Google Scholar
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): 20–29.Google Scholar
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): 48–70.Google Scholar
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): 523–537.CrossRefGoogle ScholarPubMed
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): 914–928.Google Scholar
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): S98–110.Google Scholar
112.Medalia, A, Saperstein, AM. Does cognitive remediation for schizophrenia improve functional outcomes? Curr Opin Psychiatry. 2013; 26(2): 151–157.Google Scholar
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): 472–485.Google Scholar
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): 859–868.Google Scholar
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.Google Scholar
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): 1087–1091.Google Scholar
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): 327–336.Google Scholar
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.Google Scholar
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): 170–180.Google Scholar
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): 163–173.Google Scholar
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): 645–692.Google Scholar
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): 152–163.Google Scholar
123.Fervaha, G, Foussias, G, Agid, O, Remington, G. Neural substrates underlying effort computation in schizophrenia. Neurosci Biobehav Rev. 2013; 37(10 Pt 2): 2649–2665.Google Scholar
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.Google Scholar
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): 645–692.Google Scholar
126.Köster, LS, Carbon, M, Correll, CU. Emerging drugs for schizophrenia: an update. Expert Opin Emerg Drugs. 2014; 19: 1–21. [Epub ahead of print] PMID: 25234340.Google Scholar
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): 418–428.Google Scholar
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): 30–53.Google Scholar
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): 180–190.Google Scholar
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): 600–610.Google Scholar
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): 611–622.Google Scholar
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): 82–89.CrossRefGoogle ScholarPubMed
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): 152–163.Google Scholar
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): 312–320.Google Scholar
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): 188–194.Google Scholar
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): 633–647.Google Scholar
137.Rummel, C, Kissling, W, Leucht, S. Antidepressants for the negative symptoms of schizophrenia. Cochrane Database Syst Rev. 2006; (3): CD005581.Google Scholar
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): 604–610.Google Scholar
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): 174–179.Google Scholar
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): 1259–1266.Google Scholar
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): 158–168.Google Scholar
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): 861–868.Google Scholar
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): 206–212.Google Scholar
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): 974–981.Google Scholar
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): 159–166.Google Scholar
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.Google Scholar
147.Tuominen, HJ, Tiihonen, J, Wahlbeck, K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev. 2006; (2): CD003730. Review. PubMed PMID:16625590.Google Scholar
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): 1593–1602.Google Scholar
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): 320–327.Google Scholar
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): 1102–1107.Google Scholar
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): 434–441.Google Scholar
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. http://www.addextherapeutics.com/investors/press-releases/news-details/article/addex-reports-top-line-data-from-a-successful-phase-2a-clinical-study-with-adx71149-in-schizophrenia.Google Scholar
153.Lavoie, S, Murray, MM, Deppen, P, et al. Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients. Neuropsychopharmacology. 2008; 33(9): 2187–2199.Google Scholar
154.Kantrowitz, JT, Malhotra, AK, Cornblatt, B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010; 121(1–3): 125–130.Google Scholar
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): 1196–1204.Google Scholar
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): 4603–4614.Google Scholar
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): 637–646.Google Scholar
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): 103–111.Google Scholar
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): 1267–1275.Google Scholar
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): 367–377.Google Scholar
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): 16–42.Google Scholar
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): 1033–1039.Google Scholar
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): 421–427.Google Scholar
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): 63–68.Google Scholar
165.Schubert, MH, Young, KA, Hicks, PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry. 2006; 60(6): 530–533.Google Scholar
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): 218–229.Google Scholar
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): 169–182.Google Scholar
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): 133–141.Google Scholar
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): 96–105.Google Scholar
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): 375–383.Google Scholar
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): 495–499.Google Scholar
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): 179–184.Google Scholar
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): 1351–1362.Google Scholar
174.Barch, DM, Carter, CS. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr Res. 2005; 77(1): 43–58.Google Scholar
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): 241–252.Google Scholar
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): 2140–2149.Google Scholar
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): 106–113.Google Scholar
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): 116–122.Google Scholar
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): 289–296.Google Scholar
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.Google Scholar
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): 505–513.Google Scholar
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): 169–176.Google Scholar
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): 361–368.Google Scholar
184.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2): 261–276.Google Scholar
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): 538–546.Google Scholar
186.Andreasen, NC. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry Suppl. 1989; 7: 49–58.Google Scholar
187.Axelrod, BN, Goldman, RS, Alphs, LD. Validation of the 16-item Negative Symptom Assessment. J Psychiatr Res. 1993; 27(3): 253–258.Google Scholar
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): 848–859.Google Scholar
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): 838–844.Google Scholar
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): 538–545.Google Scholar
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): 532–542.Google Scholar
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): 151–155.Google Scholar
193.Nasreddine, Z. The Montreal Cognitive Assessment. http://www.mocatest.org.Google Scholar
194.Gioia, GA, Isquith, PK, Guy, SC, Kenworthy, L. Behavior rating inventory of executive function. Child Neuropsychol. 2000; 6(3): 235–238.Google Scholar
195.Opler, M, Antonius, D, Correll, CU. New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT). Unpublished rating instrument.Google Scholar