A Review of Pharmacological Strategy for Cognitive Deficits in Schizophrenia

Dong-Wook Jeon; Do-Un Jung; Bo-Geum Kong; Je-Wook Kang; Jung-Joon Moon; Joo-Cheol Shim

doi:10.16946/kjsr.2014.17.2.55

Journal List > Korean J Schizophr Res > v.17(2) > 1057803

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Jeon, Jung, Kong, Kang, Moon, and Shim: A Review of Pharmacological Strategy for Cognitive Deficits in Schizophrenia

Original Article

Korean J Schizophr Res 2014;17(2):55-62.

Published online: 20 January 2014

DOI: https://doi.org/10.16946/kjsr.2014.17.2.55

A Review of Pharmacological Strategy for Cognitive Deficits in Schizophrenia

Dong-Wook Jeon, MD¹, Do-Un Jung, MD, PhD¹, Bo-Geum Kong, MD, PhD¹, Je-Wook Kang, MD, PhD¹, Jung-Joon Moon, MD¹, Joo-Cheol Shim, MD, PhD^2,

¹Department of Psychiatry, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea

²Department of Psychiatry Shim Joo-Cheol Clinic, Busan, Korea

Address for correspondence: Joo-Cheol Shim, Department of Psychiatry Shim Joo-Cheol Clinic, Inje Medical Center Building B-1301, 785 Gaya-daero, Busanjin-gu, Busan 614-030, Korea Tel: 051-988-8275, Fax: 051-894-2532 E-mail: shimjch@hotmail.com

Received 26 August 2014 Revised 19 September 2014 Accepted 20 September 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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. (Korean J Schizophr Res 2014;17: 55–62)

Keywords: Schizophrenia, Cognition, Pharmacotherapy.

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Table 1.

The MATRICS consensus cognitive battery¹¹⁾

Test	Domain
Trail Making Test, Part A	Speed of processing
Brief Assessment of Cognition in Schizophrenia, symbol coding subtest	Speed of processing
Hopkins Verbal Learning Test-Revised, immediate recall (three learning trials only)	Verbal learning
Wechsler Memory Scale, 3rd ed., spatial span subtest	Working memory (nonverbal)
Letter-Number Span test	Working memory (verbal)
Neuropsychological Assessment Battery, mazes subtest	Reasoning and problem solving
Brief Visuospatial Memory Test-Revised	Visual learning
Category fluency test, animal naming	Speed of processing
Mayer-Salovey-Caruso Emotional intelligence test, managing emotions branch	Social cognition

Continuous Performance Test, Identical Paris version Attention/vigilance

Table 2.

Candidate Co-primary test measures for schizophrenia cognition trials by the NIMH-MATRICS group¹²⁾

Measurement method	Co-primary measure
Laboratory based measure of functional capacity	Test of Adaptive Behavior in Schizophrenia (TABS)
	The UCSD Performance-based Skills Assessmenr (UPSA)
	The Independent Living Scales (ILS)
Interview based measure	The Cognitive Assessment Interview (CAI)
	The Global Assessment of Function from CAI
	CGI for Cognitive impairment

Table 3.

Promising 9 classes of agents identified by FDA-MATRICS consensus meeting¹⁵⁾

D1-dopamine receptor agonists
α-amino-3-hydroxy-5methyl–4-isoxazolepropionate (AMPA)
glutamatergic receptor agonists
α2-adrenergic receptor agonists
NMDA glutamatergic receptor agonists
Metabotrophic glutamate receptor agonists
Glycine reuptake inhibitors
M1 muscarinic receptor agonists
GABA A R subtype selective agonists
Alpha 7 nicotinic receptor

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