Elsevier

Schizophrenia Research

Volume 72, Issue 1, 15 December 2004, Pages 29-39
Schizophrenia Research

Identification of separable cognitive factors in schizophrenia

https://doi.org/10.1016/j.schres.2004.09.007Get rights and content

Abstract

One of the primary goals in the NIMH initiative to encourage development of new interventions for cognitive deficits in schizophrenia, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), has been to develop a reliable and valid consensus cognitive battery for use in clinical trials. Absence of such a battery has hampered standardized evaluation of new treatments and, in the case of pharmacological agents, has been an obstacle to FDA approval of medications targeting cognitive deficits in schizophrenia. A fundamental step in developing such a battery was to identify the major separable cognitive impairments in schizophrenia. As part of this effort, we evaluated the empirical evidence for cognitive performance dimensions in schizophrenia, emphasizing factor analytic studies. We concluded that seven separable cognitive factors were replicable across studies and represent fundamental dimensions of cognitive deficit in schizophrenia: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, Reasoning and Problem Solving, and Verbal Comprehension. An eighth domain, Social Cognition, was added due to recent increased interest in this area and other evidence of its relevance for clinical trials aiming to evaluate the impact of potential cognitive enhancers on cognitive performance and functional outcome. Verbal Comprehension was not considered appropriate for a cognitive battery intended to be sensitive to cognitive change, due to its resistance to change. The remaining seven domains were recommended for inclusion in the MATRICS-NIMH consensus cognitive battery and will serve as the basic structure for that battery. These separable cognitive dimensions also have broader relevance to future research aimed at understanding the nature and structure of core cognitive deficits in schizophrenia.

Introduction

One of the primary initial goals of the NIMH contract on Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) has been to develop a consensus cognitive battery for use in clinical trials, as the absence of such a battery has been a major impediment to standardized evaluation of new treatments designed to alleviate cognitive deficits in this disorder. In particular, development of a standard cognitive battery through a consensus of experts would establish an accepted measurement instrument for evaluation of pharmacological agents that target cognitive deficits in schizophrenia, thereby allowing a clear pathway for FDA approval of such new medications.

In considering the development of a MATRICS-NIMH consensus cognitive battery for use in clinical trials, a key step was to determine which cognitive domains should be represented. As reported by Kern et al. (2004) elsewhere in this issue, the broad sample of experts in relevant fields that were surveyed by the MATRICS Neurocognition Committee clearly stated that they believed that reliable coverage of the major separable cognitive deficits in schizophrenia was an “essential” feature for the consensus cognitive battery. Ideally, separable in this context would refer to cognitive deficits with distinct causes or neural substrates that may therefore respond to different types of pharmacological interventions. However, at a minimum, separable should refer to cognitive deficits in schizophrenia that are distinguishable at the statistical or analytic level, such as in the results of factor analytic studies. There is an extensive literature seeking to delineate the nature of cognitive deficits in schizophrenia (Braff, 1993, Goldberg and Green, 2002, Nuechterlein and Dawson, 1984) and it is clear that these deficits are enduring, core features of this illness (Censits et al., 1997, Gold, 2004, Green and Nuechterlein, 1999, Nuechterlein et al., 1992). However, there has until now been no consensus agreement on a standard way to divide the most prominent cognitive deficits into key dimensions or domains.

Extensive research using neuropsychological test batteries has demonstrated that schizophrenia patients, as a whole, do show certain characteristic profiles of cognitive deficits (Heaton et al., 2001, Heinrichs and Zakzanis, 1998, Saykin et al., 1991, Saykin et al., 1994). Some investigators have suggested that deficits in a number of cognitive domains may share a common cause (Andreasen et al., 1998, Cohen et al., 1999, Goldman-Rakic, 1994, Nuechterlein and Dawson, 1984). However, individual patients may show meaningful variations in the modal profile (Palmer et al., 1997, Weickert et al., 2000) and other researchers have suggested that different types of cognitive deficits may have different neurobiological substrates (e.g., working memory versus episodic memory) and may respond to different treatment approaches. Thus, it is important to represent the major separable cognitive domains in a battery for clinical trials. Unfortunately, the ways that the cognitive domains have been divided has varied from study to study, depending on the preferences of the individual investigative teams and the range of measures employed. To reach a consensus on the major separable cognitive factors in schizophrenia, the authors of this article served as a subcommittee of the MATRICS Neurocognition Committee to review the available empirical evidence and to make recommendations regarding the separable cognitive domains to be included in the MATRICS consensus cognitive battery for clinical trials.

Section snippets

Method

To delineate the major dimensions of cognitive deficit in schizophrenia, the authors established a set of principles for identification of the cognitive domains. The following principles were emphasized:

  • (1)

    Dimensions that were independent or only weakly intercorrelated were sought, such that they could be viewed as separable contributors to functional outcome and as potentially separate targets for new treatments.

  • (2)

    Only cognitive dimensions that had been replicated across several studies of

Results

The result of this process was the identification of six separable cognitive dimensions in schizophrenia. We present these cognitive domains ordered from relatively basic to high-level cognitive processes, rather than in the order in which factors emerged from individual studies, as the latter varied from study to study. To help the reader see the support for each dimension across studies and the nature of the cognitive domain, a table showing the studies identifying a similar factor and the

Discussion

As detailed above, the review of available factor analytic evidence for separable cognitive dimensions in schizophrenia yielded six domains that could be recommended for inclusion in the MATRICS-NIMH consensus cognitive battery for clinical trials: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, and Reasoning and Problem Solving. A seventh dimension, Verbal Comprehension, was identified but not recommended for inclusion due to

Acknowledgements

An earlier version of this paper was presented at: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Conference #1: Identifying Cognitive Targets and Establishing Criteria for Test Selection, Bethesda, MD. Support for this conference came from NIMH Contract MH22006 (S.R. Marder, P.I., M.F. Green, Co-P.I.). Additional support for the preparation of this article came from Center grant MH66286 (K.H. Nuechterlein, P.I.).

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