Korean J Schizophr Res.  2014 Oct;17(2):55-62. 10.16946/kjsr.2014.17.2.55.

A Review of Pharmacological Strategy for Cognitive Deficits in Schizophrenia

• Jeon DW
• Jung DU
• Kong BG
• Kang JW
• Moon JJ
• Shim JC

• KMID: 2288288
• DOI: http://doi.org/10.16946/kjsr.2014.17.2.55

Abstract

Cognitive deficit is frequently observed in patients with schizophrenia. It is significantly associated with functional outcome. In the past 20 years, due to significant advances on the concept of schizophrenia, cognitive deficit has been accepted as a core feature. In the DSM-5, cognitive deficit does not introduce diagnostic criteria of schizophrenia, but did one dimension of diagnosis of psychosis. Existing schizophrenia drugs are effective in treatment of positive symptoms of schizophrenia, but lack of effectiveness on improving cognitive function. Led by NIMH (National Institute of Mental Health), the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) meeting was conducted in order to achieve consensus on measuring tools and neuropharmacological targets for clinical trials for development of new drugs for improvement of cognitive function in schizophrenia. At the MATRICS consensus meeting, glutamatergic modulators and nicotinic and muscarinic agonists are expected to be promising, but should be proven by a double-blind placebo-controlled multicenter study for patients.

Keyword

Schizophrenia; Cognition; Pharmacotherapy

MeSH Terms

Cognition
Consensus
Diagnosis
Drug Therapy
Humans
Muscarinic Agonists
National Institute of Mental Health (U.S.)
Psychotic Disorders
Schizophrenia*
Muscarinic Agonists

Reference

References

1. Green MF. Stimulating the development of drug treatments to improve cognition in schizophrenia. Annu Rev Clin Psychol. 2007; 3:159–180.

2. Green MF, Harvey PD. Cognition in schizophrenia: Past, present, and future. Schizophrenia Research: Cognition. 2014; 1:1–9.

3. Tonmoy S, Harvey P. Cognition in schizophrenia: Impairments, Importance and Treatment Strategies. 1st ed.New York: Oxford university press;2000. p. p3–335.

4. Opler LA, Medalia A, Opler MG, Stahl SM. Pharmacotherapy of cognitive deficits in schizophrenia. CNS Spectr. 2014; 19:142–156.

5. Kahn RS, Keefe RS. Schizophrenia is a cognitive illness: Time for a change in focus. JAMA Psychiatry. 2013; 70:1107–1112.

6. Green MF. Commentary on “cognition in schizophrenia”. Eur Neuropsychopharmacol. 2013; 23:786–787.

7. Kirkpatrick B, Fenton WS, Carpenter WT, Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006; 32:214–219.

8. Keefe RS, Buchanan RW, Marder SR, Schooler NR, Dugar A, Zi-vkov M, et al. Clinical trials of potential cognitive-enhancing drugs in schizophrenia: What have we learned so far? Schizophr Bull. 2013; 39:417–435.

9. Goldberg TE, Gomar JJ. Comment on “cognition in schizophrenia: Summary nice consultation meeting 2012”. Eur Neuropsychopharmacol. 2013; 23:788–789.

10. Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, 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; 56:301–307.

11. Lee SH, Jung HT, Chung YC. Development of New Drug for Cognitive Enhancement of Schizophrenia-Introduction of Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS). Korean J Psychopharmacol. 2005; 16:272–278.

12. Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, et al. The MATRICS consensus cognitive battery, part 1: Test selection, reliability, and validity. Am J Psychiatry. 2008; 165:203–213.

13. Nutt D, Gispen CC, Arango C, Keefe RS, Penades R, Murphy DG, et al. Cognition in schizophrenia: Summary nice consultation meeting 2012. Eur Neuropsychopharmacol. 2013; 23:769–778.

14. Pinkham AE, Penn DL, Green MF, Buck B, Healey K, Harvey PD. The social cognition psychometric evaluation study: Results of the expert survey and RAND panel. Schizophr Bull. 2014; 40:813–823.

15. Green MF, Lee J, Ochsner KN. Adapting social neuroscience measures for schizophrenia clinical trials, part 1: Ferrying paradigms across perilous waters. Schizophr Bull. 2013; 39:1192–1200.

16. Tamminga CA. The neurobiology of cognition in schizophrenia. J Clin Psychiatry. 2006; 67:9–13.

17. Javitt DC. Glutamatergic theories of schizophrenia. Isr J Psychiatry Relat Sci. 2010; 47:4–16.

18. Lin CH, Lane HY, Tsai GE. Glutamate signaling in the pathophysiology and therapy of schizophrenia. Pharmacol Biochem Behav. 2012; 100:665–677.

19. Yasuhara A, Chaki S. Metabotropic glutamate receptors: Potential drug targets for psychiatric disorders. Open Med Chem J. 2010; 4:20–36.

20. Paz RD, Tardito S, Atzori M, Tseng KY. Glutamatergic dysfunction in schizophrenia: From basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol. 2008; 18:773–786.

21. Lee JG, Lee SW, Lee BJ, Park SW, Kim GM, Kim YH. Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: A placebocontrolled pilot study. Psychiatry Investig. 2012; 9:166–173.

22. Ochoa EL, Lasalde DJ. Cognitive deficits in schizophrenia: Focus on neuronal nicotinic acetylcholine receptors and smoking. Cell Mol Neurobiol. 2007; 27:609–639.

23. Arneric SP, Holladay M, Williams M. Neuronal nicotinic receptors: A perspective on two decades of drug discovery research. Biochem Pharmacol. 2007; 74:1092–1101.

24. Shim JC, Jung DU, Jung SS, Seo YS, Cho DM, Lee JH, et al. Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: A randomized double-blind placebocontrolled trial. Neuropsychopharmacology. 2012; 37:660–668.

25. Lee SW, Lee JG, Lee BJ, Kim YH. A 12-week, double-blind, placebocontrolled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Int Clin Psychopharmacol. 2007; 22:63–68.

26. Lee BJ, Lee JG, Kim YH. A 12-week, double-blind, placebocontrolled trial of donepezil as an adjunct to haloperidol for treating cognitive impairments in patients with chronic schizophrenia. J Psychopharmacol. 2007; 21:421–427.