1.Kirkpatrick, B, Strauss, GP, Nguyen, L, et al. The brief negative symptom scale: psychometric properties. Schizophr Bull. 2011; 37(2): 300–305.
2.Blanchard, JJ, Cohen, AS. The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr Bull. 2006; 32(2): 238–245.
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.
4.Foussias, G, Remington, G. Negative symptoms in schizophrenia: avolition and Occam's razor. Schizophr Bull. 2010; 36(2): 359–369.
5.Pizzagalli, DA. The “anhedonia paradox” in schizophrenia: insights from affective neuroscience. Biol Psychiatry. 2010; 67(10): 899–901.
6.Cohen, AS, Minor, KS. Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophr Bull. 2010; 36(1): 143–150.
7.Buchanan, RW. Persistent negative symptoms in schizophrenia: an overview. Schizophr Bull. 2007; 33(4): 1013–1022.
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.
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.
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.
11.Galderisi, S, Maj, M. Deficit schizophrenia: an overview of clinical, biological and treatment aspects. Eur Psychiatry. 2009; 24(8): 493–500.
12.Correll, CU, Kishimoto, T, Nielsen, J, Kane, JM. Quantifying clinical relevance in the treatment of schizophrenia. Clin Ther. 2011; 33(12): B16–B39.
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): 11–13.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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): 549–559.
34.Gold, JM, Weinberger, DR. Cognitive deficits and the neurobiology of schizophrenia. Curr Opin Neurobiol. 1995; 5(2): 225–230.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
45.Bozikas, VP, Kosmidis, MH, Kioperlidou, K, Karavatos, A. Relationship between psychopathology and cognitive functioning in schizophrenia. Compr Psychiatry. 2004; 45(5): 392–400.
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.
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.
48.Keefe, RS, Bilder, RM, Harvey, PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology. 2006; 31(9): 2033–2046.
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.
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.
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): 315–336.
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.
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.
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.
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.
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.
58.Keefe, RS. Should cognitive impairment be included in the diagnostic criteria for schizophrenia? World Psychiatry. 2008; 7(1): 22–28.
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): 310–319.
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.
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.
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.
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.
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.
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.
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.
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.
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: 1203–1208.
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.
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.
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): 58–62.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
88.Palmer, BW, Heaton, RK, Paulsen, JS, et al. Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology. 1997; 11(3): 437–446.
89.Keefe, RSE, Eesley, CE, Poe, M. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry. 2005; 57(6): 688–691.
90.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996; 153(3): 321–330.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
112.Medalia, A, Saperstein, AM. Does cognitive remediation for schizophrenia improve functional outcomes? Curr Opin Psychiatry. 2013; 26(2): 151–157.
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.
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.
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): 1087–1091.
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.
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): 170–180.
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.
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.
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.
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.
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): 645–692.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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): 604–610.
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.
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.
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.
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.
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.
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.
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.
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): 1593–1602.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
165.Schubert, MH, Young, KA, Hicks, PB. Galantamine improves cognition in schizophrenic patients stabilized on risperidone. Biol Psychiatry. 2006; 60(6): 530–533.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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): 505–513.
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.
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.
184.Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2): 261–276.
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.
186.Andreasen, NC. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry Suppl. 1989; 7: 49–58.
187.Axelrod, BN, Goldman, RS, Alphs, LD. Validation of the 16-item Negative Symptom Assessment. J Psychiatr Res. 1993; 27(3): 253–258.
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.
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.
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.
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.
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.
194.Gioia, GA, Isquith, PK, Guy, SC, Kenworthy, L. Behavior rating inventory of executive function. Child Neuropsychol. 2000; 6(3): 235–238.
195.Opler, M, Antonius, D, Correll, CU. New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT). Unpublished rating instrument.