Abstract
Neurocognitive deficits affect nearly every aspect of psychosocial and functional outcomes in schizophrenia. In particular, deficits to executive functioning and verbal memory have been found to predict clinical and psychosocial outcomes at every stage of the psychosis spectrum, from clinically high-risk populations to chronic schizophrenia. Baseline cognitive indices provide clinical and prognostic information about daily functioning, community integration, and quality of life and can serve as predictors of health-care-related outcomes as well. While psychotic symptoms of schizophrenia are amenable to pharmacologic interventions, treatment strategies for cognitive symptoms are lacking. From a drug discovery perspective, modulation of glutamatergic and cholinergic pathways is promising, but there are no current FDA-approved medications for the treatment of cognitive symptoms in schizophrenia. As therapeutic options for this disorder continue to grow, including pharmacology, neuromodulation, cognitive remediation, and combinations thereof, these treatments will be made particularly potent if they are applied to biomarker-identified sensitive subgroups of patients.
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References
Vassos E, Sham PC, Cai G, Deng H, Liu X, Sun X, et al. Correlation and familial aggregation of dimensions of psychosis in affected sibling pairs from China. Br J Psychiatry. 2008;193:305–10.
McGrath JA, Avramopoulos D, Lasseter VK, Wolyniec PS, Fallin MD, Liang K-Y, et al. Familiality of novel factorial dimensions of schizophrenia. Arch Gen Psychiatry. 2009;66:591–600.
Savage RM, Wiener HW, Nimgaonkar V, Devlin B, Calkins ME, Gur RE, et al. Heritability of functioning in families with schizophrenia in relation to neurocognition. Schizophr Res. 2012;139:105–9.
Bromley E, Brekke JS. Assessing function and functional outcome in schizophrenia. Curr Top Behav Neurosci. 2010;4:3–21.
Harvey PD. Assessing disability in schizophrenia: tools and contributors. J Clin Psychiatry. 2014;75:e27.
Heinrichs RW, Statucka M, Goldberg J, McDermid Vaz S. The University of California Performance Skills Assessment (UPSA) in schizophrenia. Schizophr Res. 2006;88:135–41.
Mausbach BT, Harvey PD, Goldman SR, Jeste DV, Patterson TL. Development of a brief scale of everyday functioning in persons with serious mental illness. Schizophr Bull. 2007;33:1364–72.
Moore RC, Fazeli PL, Patterson TL, Depp CA, Moore DJ, Granholm E, et al. UPSA-M: feasibility and initial validity of a mobile application of the UCSD performance-based skills assessment. Schizophr Res. 2015;164:187–92.
Velligan DI, Fredrick M, Mintz J, Li X, Rubin M, Dube S, et al. The reliability and validity of the MATRICS functional assessment battery. Schizophr Bull. 2014;40:1047–52.
Joseph J, Kremen WS, Glatt SJ, Franz CE, Chandler SD, Liu X, et al. Assessment of Lifespan Functioning Attainment (ALFA) scale: a quantitative interview for self-reported current and functional decline in schizophrenia. J Psychiatr Res. 2015;65:102–7.
Schaefer J, Giangrande E, Weinberger DR, Dickinson D. The global cognitive impairment in schizophrenia: consistent over decades and around the world. Schizophr Res. 2013;150:42–50.
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;158:156–62.
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 schizophrenia patients. Biol Psychiatry. 2003;53:422–30.
Wittorf A, Wiedemann G, Buchkremer G, Klingberg S. Prediction of community outcome in schizophrenia 1 year after discharge from inpatient treatment. Eur Arch Psychiatry Clin Neurosci. 2008;258:48–58.
Friedman JI, Harvey PD, Coleman T, Moriarty PJ, Bowie C, Parrella M. Six-year follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer’s disease and normal aging. Am J Psychiatry. 2001;158:1441–8.
Bodnar M, Malla A, Joober R, Lepage M. Cognitive markers of short-term clinical outcome in first-episode psychosis. Br J Psychiatry. 2008;193:297–304.
Chang WC, Ming Hui CL, Yan Wong GH, Wa Chan SK, Ming Lee EH, Hai Chen EY. Symptomatic remission and cognitive impairment in first-episode schizophrenia: a prospective 3-year follow-up study. J Clin Psychiatry. 2013;74:e1046–53.
Hofer A, Bodner T, Kaufmann A, Kemmler G, Mattarei U, Pfaffenberger NM, et al. Symptomatic remission and neurocognitive functioning in patients with schizophrenia. Psychol Med. 2011;41:2131–9.
Andreou C, Roesch-Ely D, Veckenstedt R, Bohn F, Aghotor J, Köther U, et al. Predictors of early stable symptomatic remission after an exacerbation of schizophrenia: the significance of symptoms, neuropsychological performance and cognitive biases. Psychiatry Res. 2013;210:729–34.
Helldin L, Kane JM, Karilampi U, Norlander T, Archer T. Remission and cognitive ability in a cohort of patients with schizophrenia. J Psychiatr Res. 2006;40:738–45.
Brissos S, Dias VV, Balanzá-Martinez V, Carita AI, Figueira ML. Symptomatic remission in schizophrenia patients: relationship with social functioning, quality of life, and neurocognitive performance. Schizophr Res. 2011;129:133–6.
Niendam TA, Bearden CE, Zinberg J, Johnson JK, O’Brien M, Cannon TD. The course of neurocognition and social functioning in individuals at ultra high risk for psychosis. Schizophr Bull. 2007;33:772–81.
Lin A, Wood SJ, Nelson B, Brewer WJ, Spiliotacopoulos D, Bruxner A, et al. Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high risk for psychosis. Schizophr Res. 2011;132:1–7.
Carrión RE, McLaughlin D, Goldberg TE, Auther AM, Olsen RH, Olvet DM, et al. Prediction of functional outcome in individuals at clinical high risk for psychosis. JAMA Psychiat. 2013;70:1133–42.
Semkovska M, Bédard M-A, Godbout L, Limoge F, Stip E. Assessment of executive dysfunction during activities of daily living in schizophrenia. Schizophr Res. 2004;69:289–300.
Fujii DE, Wylie AM. Neurocognition and community outcome in schizophrenia: long-term predictive validity. Schizophr Res. 2003;59:219–23.
Seidman LJ, Shapiro DI, Stone WS, Woodberry KA, Ronzio A, Cornblatt BA, et al. Association of neurocognition with transition to psychosis: baseline functioning in the second phase of the north American prodrome longitudinal study. JAMA Psychiat. 2016;73:1239–48.
Seidman LJ, Giuliano AJ, Meyer EC, Addington J, Cadenhead KS, Cannon TD, et al. Neuropsychology of the prodrome to psychosis in the NAPLS consortium: relationship to family history and conversion to psychosis. Arch Gen Psychiatry. 2010;67:578–88.
Addington J, Cornblatt BA, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, et al. At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry. 2011;168:800–5.
Sawada K, Kanehara A, Eguchi S, Tada M, Satomura Y, Suga M, et al. Identifying neurocognitive markers for outcome prediction of global functioning in ultra-high-risk for psychosis and first episode psychosis. Psychiatry Clin Neurosci. 2017;71:318–27.
Jordan G, Lutgens D, Joober R, Lepage M, Iyer SN, 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:e566–72.
Ventura J, Hellemann GS, Thames AD, Koellner V, Nuechterlein KH. Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res. 2009;113:189–99.
Thomas ML, Green MF, Hellemann G, Sugar CA, Tarasenko M, Calkins ME, et al. Modeling deficits from early auditory information processing to psychosocial functioning in schizophrenia. JAMA Psychiat. 2017;74:37–46.
Woonings FMJ, Appelo MT, Kluiter H, Slooff CJ, van den Bosch RJ. Learning (potential) and social functioning in schizophrenia. Schizophr Res. 2003;59:287–96.
Helldin L, Hjärthag F, Olsson A-K, Harvey PD. Cognitive performance, symptom severity, and survival among patients with schizophrenia spectrum disorder: a rospective 15-year study. Schizophr Res. 2015;169:141–6.
Frydecka D, Beszłej JA, Gościmski P, Kiejna A, Misiak B. Profiling cognitive impairment in treatment-resistant schizophrenia patients. Psychiatry Res. 2016;235:133–8.
Vinogradov S, Fisher M, Warm H, Holland C, Kirshner MA, Pollock BG. The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia. Am J Psychiatry. 2009;166:1055–62.
Singh J, Kour K, Jayaram MB. Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database System Rev. 2012;1:CD007967.
Keefe RSE, Meltzer HA, Dgetluck N, Gawryl M, Koenig G, Moebius HJ, et al. Randomized, double-blind, placebo-controlled study of encenicline, an α7 nicotinic acetylcholine receptor agonist, as a treatment for cognitive impairment in schizophrenia. Neuropsychopharmacology. 2015;40:3053–60.
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AFT, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci U S A. 2013;110:12078–83.
Thomas EHX, Bozaoglu K, Rossell SL, Gurvich C. The influence of the glutamatergic system on cognition in schizophrenia: a systematic review. Neurosci Biobehav Rev. 2017;77:369–87.
Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G, et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry. 2010;71:138–49.
Chengappa KNR, Turkin SR, DeSanti S, Bowie CR, Brar JS, Schlicht PJ, et al. A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in schizophrenia. Schizophr Res. 2012;142:145–52.
Tsai G, Yang P, Chung LC, Lange N, Coyle JT. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. 1998;44:1081–9.
Kantrowitz JT, Malhotra AK, Cornblatt B, Silipo G, Balla A, Suckow RF, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010;121:125–30.
Tsai GE. Ultimate translation: developing therapeutics targeting on N-methyl-d-aspartate receptor. Adv Pharmacol. 2016;76:257–309.
de Lucena D, Fernandes BS, Berk M, Dodd S, Medeiros DW, Pedrini M, et al. Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine. J Clin Psychiatry. 2009;70:1416–23.
Veerman SRT, Schulte PFJ, Deijen JB, de Haan L. Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study. Psychol Med. 2017;47:363–75.
Light GA, Zhang W, Joshi YB, Bhakta S, Talledo JA, Swerdlow NR. Single-dose memantine improves cortical oscillatory response dynamics in patients with schizophrenia. Neuropsychopharmacology. 2017;42:2633–9.
Lieberman JA, Papadakis K, Csernansky J, Litman R, Volavka J, Jia XD, et al. A randomized, placebo-controlled study of memantine as adjunctive treatment in patients with schizophrenia. Neuropsychopharmacology. 2009;34:1322–9.
Dickinson D, Tenhula W, Morris S, Brown C, Peer J, Spencer K, et al. A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia. Am J Psychiatry. 2010;167:170–80.
d’Amato T, Bation R, Cochet A, Jalenques I, Galland F, Giraud-Baro E, et al. A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia. Schizophr Res. 2011;125:284–90.
Gomar JJ, Valls E, Radua J, Mareca C, Tristany J, del Olmo F, et al. A multisite, randomized controlled clinical trial of computerized cognitive remediation therapy for schizophrenia. Schizophr Bull. 2015;41:1387–96.
Trapp W, Landgrebe M, Hoesl K, Lautenbacher S, Gallhofer B, Günther W, 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.
Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153:321–30.
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;163:418–25.
Swerdlow NR, Tarasenko M, Bhakta SG, Talledo J, Alvarez AI, Hughes EL, et al. Amphetamine enhances gains in auditory discrimination training in adult schizophrenia patients. Schizophr Bull. 2017;43:872–80.
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Molina, J., Tsuang, M.T. (2020). Neurocognition and Treatment Outcomes in Schizophrenia. In: Shrivastava, A., De Sousa, A. (eds) Schizophrenia Treatment Outcomes. Springer, Cham. https://doi.org/10.1007/978-3-030-19847-3_5
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DOI: https://doi.org/10.1007/978-3-030-19847-3_5
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