Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-02T20:21:01.778Z Has data issue: false hasContentIssue false
  • English
  • Français

Cognitive impairment in schizophrenia: the great unmet need

Published online by Cambridge University Press:  18 December 2015

Ralph Aquila  and
Leslie Citrome
Ralph Aquila*
Affiliation:
Fountain House, New York City, New York, USA Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York City, New York, USA
Leslie Citrome
Affiliation:
Department of Psychiatry & Behavioral Sciences, New York Medical College, Valhalla, New York, USA
*
*Address for correspondence: Ralph Aquila, Sidney R. Baer Jr. Center, 347 West 37th Street, New York, NY 10018. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Cognitive impairment in schizophrenia is present in almost all persons with the disorder and can be a substantial obstacle to efforts in the recovery process. In clinical research, cognition is assessed through neuropsychological testing as well as by different types of structured instruments focusing on function. Although nonpharmacological interventions such as cognitive remediation have been therapeutic, particularly in combination with vocational rehabilitation and supported employment, these modalities are not always easy to access. Pharmacological interventions are in development and have principally focused on the dopamine, glutamate, and acetylcholine neurotransmitter systems, aiming to target the dorsolateral prefrontal cortex and its interactions with other brain regions.

Keywords

Cognitionimpairmentpsychosisreturn to functioningschizophrenia
Type
CME Review Article
Information
CNS Spectrums , Volume 20 , Issue S1: CME SUPPLEMENT , December 2015 , pp. 32 - 40
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

This activity is supported by an unrestricted educational grant from FORUM Pharmaceuticals, LLC.

References

1.Aquila, R, Malamud, TJ, Sweet, T, Kelleher, JD. The store front, Fountain House, and the rehabilitation alliance. MedGenMed. 2006; 8(3): 67.Google ScholarPubMed
2.Keefe, RS, Eesley, CE, Poe, MP. Defining a cognitive function decrement in schizophrenia. Biol Psychiatry. 2005; 57(6): 688–691.CrossRefGoogle ScholarPubMed
3.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.CrossRefGoogle ScholarPubMed
4.Lindenmayer, JP, McGurk, SR, Mueser, KT, et al. A randomized controlled trial of cognitive remediation among inpatients with persistent mental illness. Psychiatr Serv. 2008; 59(3): 241–247.CrossRefGoogle ScholarPubMed
5.Chan, JY, Hirai, HW, Tsoi, KK. Can computer-assisted cognitive remediation improve employment and productivity outcomes of patients with severe mental illness? A meta-analysis of prospective controlled trials. J Psychiatr Res. 2015; 68: 293–300.CrossRefGoogle ScholarPubMed
6.Kaneko, Y, Keshavan, M. Cognitive remediation in schizophrenia. Clin Psychopharmacol Neurosci. 2012; 10(3): 125–135.Google ScholarPubMed
7.McGurk, SR, Mueser, KT, Xie, H, et al. Cognitive enhancement treatment for people with mental illness who do not respond to supported employment: a randomized controlled trial. Am J Psychiatry. 2015; 172(9): 852–861.CrossRefGoogle Scholar
8.Kurzban, S, Davis, L, Brekke, JS. Vocational, social, and cognitive rehabilitation for individuals diagnosed with schizophrenia: a review of recent research and trends. Curr Psychiatry Rep. 2010; 12(4): 345–355.CrossRefGoogle ScholarPubMed
9.Folstein, MF, Folstein, SE, McHugh, PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3): 189–198.CrossRefGoogle ScholarPubMed
10.Nasreddine, ZS, Phillips, NA, Bédirian, V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4): 695–699.CrossRefGoogle Scholar
11.Morosini, PL, Magliano, L, Brambilla, L, Ugolini, S, Pioli, R. Development, reliability and acceptability of a new version of the DSM-IV Social and Occupational Functioning Assessment Scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand. 2000; 101(4): 323–329.Google ScholarPubMed
12.Nafees, B, van Hanswijck de Jonge, P, et al. Reliability and validity of the Personal and Social Performance scale in patients with schizophrenia. Schizophr Res. 2012; 140(1–3): 71–76.CrossRefGoogle ScholarPubMed
13.Patterson, TL, Goldman, S, McKibbin, CL, Hughs, T, Jeste, DV. UCSD Performance-Based Skills Assessment: development of a new measure of everyday functioning for severely mentally ill adults. Schizophr Bull. 2001; 27(2): 235–245.CrossRefGoogle ScholarPubMed
14.Keefe, RS, Haig, GM, Marder, SR, et al. Report on ISCTM Consensus Meeting on Clinical Assessment of Response to Treatment of Cognitive Impairment in Schizophrenia. Schizophr Bull. In press. DOI: 10.1093/schbul/sbv111.Google Scholar
15.Rosenheck, R, Leslie, D, Keefe, R, et al. Barriers to employment for people with schizophrenia. Am J Psychiatry. 2006; 163(3): 411–417.CrossRefGoogle ScholarPubMed
16.Schonebaum, AD, Boyd, JK, Dudek, KJ. A comparison of competitive employment outcomes for the clubhouse and PACT models. Psychiatr Serv. 2006; 57(10): 1416–1420.CrossRefGoogle ScholarPubMed
17.Norman, C. The Fountain House movement, an alternative rehabilitation model for people with mental health problems, members’ descriptions of what works. Scand J Caring Sci. 2006; 20(2): 184–192.CrossRefGoogle ScholarPubMed
18.Howes, OD, Kapur, S. The dopamine hypothesis of schizophrenia: version III—the final common pathway. Schizophr Bull. 2009; 35(3): 549–562.CrossRefGoogle ScholarPubMed
19.Howes, O, McCutcheon, R, Stone, J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol. 2015; 29(2): 97–115.CrossRefGoogle Scholar
20.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.CrossRefGoogle ScholarPubMed
21.Barch, DM, Ceaser, A. Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci. 2012; 16(1): 27–34.CrossRefGoogle ScholarPubMed
22.Nielsen, RE, Levander, S, Kjaersdam Telléus, G, Jensen, SO, Østergaard Christensen, T, Leucht, S. Second-generation antipsychotic effect on cognition in patients with schizophrenia—a meta-analysis of randomized clinical trials. Acta Psychiatr Scand. 2015; 131(3): 185–196.CrossRefGoogle ScholarPubMed
23.Kantrowitz, JT, Javitt, DC. Thinking glutamatergically: changing concepts of schizophrenia based upon changing neurochemical models. Clin Schizophr Relat Psychoses. 2010; 4(3): 189–200.CrossRefGoogle ScholarPubMed
24.Tsapakis, EM, Travis, MJ. Glutamate and psychiatric disorders. Adv Psychiatr Treat. 2002; 8(3): 189–197.CrossRefGoogle Scholar
25.Moghaddam, B. Bringing order to the glutamate chaos in schizophrenia. Neuron. 2003; 40(5): 881–884.CrossRefGoogle Scholar
26.Kantrowitz, JT, Javitt, DC. Glutamate: new hope for schizophrenia treatment. Curr Psychiatry. 2011; 10(4): 69–74.Google Scholar
27.Citrome, L. Neurochemical models of schizophrenia: transcending dopamine. Curr Psychiatry. 2011; 10(9): S10–S14.Google Scholar
28.Stahl, MS. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 3rd ed. New York: Cambridge University Press; 2008.Google Scholar
29.Kantrowitz, JT, Javitt, DC. N-Methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Res Bull. 2010; 83(3–4): 108–121.CrossRefGoogle ScholarPubMed
30.Citrome, L. Unmet needs in the treatment of schizophrenia: new targets to help different symptom domains. J Clin Psychiatry. 2014; 75(Suppl 1): 21–26.CrossRefGoogle ScholarPubMed
31.Iwata, Y, Nakajima, S, Suzuki, T, et al. Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials. Mol Psychiatry. In press. DOI: 10.1038/mp.2015.68.Google Scholar
32.Birks, J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1): CD005593.Google ScholarPubMed
33.Singh, J, Kour, K, Jayaram, MB. Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database Syst Rev. 2012; 1: CD007967.Google ScholarPubMed
34.Young, JW, Geyer, MA. Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol. 2013; 86(8): 1122–1132.CrossRefGoogle ScholarPubMed
35.Levin, ED, McClernon, FJ, Rezvani, AH. Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl). 2006; 184(3–4): 523–539.CrossRefGoogle ScholarPubMed
36.Huang, M, Felix, AR, Flood, DG, et al. The novel α7 nicotinic acetylcholine receptor agonist EVP-6124 enhances dopamine, acetylcholine, and glutamate efflux in rat cortex and nucleus accumbens. Psychopharmacology (Berl). 2014; 231(23): 4541–4551.CrossRefGoogle ScholarPubMed
37.Prickaerts, J, van Goethem, NP, Chesworth, R, et al. EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors. Neuropharmacology. 2012; 62(2): 1099–1110.CrossRefGoogle ScholarPubMed
38.Keefe, RS, Meltzer, HA, Dgetluck, N, 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. In press. DOI: 10.1038/npp.2015.176.Google Scholar
39.Deardorff, WJ, Shobassy, A, Grossberg, GT. Safety and clinical effects of EVP-6124 in subjects with Alzheimer’s disease currently or previously receiving an acetylcholinesterase inhibitor medication. Expert Rev Neurother. 2015; 15(1): 7–17.CrossRefGoogle ScholarPubMed
40. Forum Pharmaceuticals. FORUM Pharmaceuticals Inc. Updates Encenicline Phase 3 Clinical Trial Programs in Alzheimer’s Disease and Cognitive Impairment in Schizophrenia. Press Release. 14 September 2015. Available at: http://www.businesswire.com/news/home/20150914005855/en/FORUM-Pharmaceuticals-Updates-Encenicline-Phase-3-Clinical. Accessed 15 September 2015.Google Scholar
41.Carruthers, SP, Gurvich, CT, Rossell, SL. The muscarinic system, cognition and schizophrenia. Neurosci Biobehav Rev. 2015; 55: 393–402.Google ScholarPubMed
42.Köster, LS, Carbon, M, Correll, CU. Emerging drugs for schizophrenia: an update. Expert Opin Emerg Drugs. 2014; 19(4): 511–531.CrossRefGoogle ScholarPubMed
43.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.CrossRefGoogle ScholarPubMed
44.Buchanan, RW, Freedman, R, Javitt, DC, Abi-Dargham, A, Lieberman, JA. Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. Schizophr Bull. 2007; 33(5): 1120–1130.CrossRefGoogle ScholarPubMed
45.Goff, DC, Hill, M, Barch, D. The treatment of cognitive impairment in schizophrenia. Pharmacol Biochem Behav. 2011; 99(2): 245–253.CrossRefGoogle ScholarPubMed