Identification of separable cognitive factors 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.).
References (67)
- et al.
Confirmatory factor analysis of the WAIS-R in patients with schizophrenia
Schizophr. Res.
(1998) - et al.
Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study
Schizophr. Res.
(1997) - et al.
The Continuous Performance Test, Identical Pairs Version (CPT-IP): I. New findings about sustained attention in normal families
J. Psychiatr. Res.
(1988) - et al.
General and specific cognitive deficits in schizophrenia
Biol. Psychiatry
(2004) Cognitive deficits as treatment targets in schizophrenia
Schizophr. Res.
(2004)- et al.
The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone
Biol. Psychiatry
(2002) - 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) - et al.
Perception of emotion and neurocognitive functioning in schizophrenia: what's the link?
Psychiatry Res.
(1998) - et al.
The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery
Schizophr. Res.
(2004) - et al.
NIMH-MATRICS survey on assessment of neurocognition in schizophrenia
Schizophr. Res.
(2004)
Maintenance and manipulation of information in schizophrenia: further evidence for impairment in the central executive component of working memory
Schizophr. Res.
Comparison of the continuous performance test with and without working memory demands in healthy controls and patients with schizophrenia
Schizophr. Res.
Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia
Biol. Psychiatry
Cognitive dysmetria as an integrative theory of schizophrenia: a dysfunction in cortical–subcortical–cerebellar circuitry
Schizophr. Bull.
Span of apprehension in schizophrenia
Working Memory
Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?
J. Abnorm. Psychology
Testing Structural Equation Models
Information processing and attention dysfunctions in schizophrenia
Schizophr. Bull.
Visual Masking: An Integrative Approach
Biosocial pathways to functional outcome in schizophrenia: a path analytic model
Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited
Cereb. Cortex
Context-processing deficits in schizophrenia: converging evidence from three theoretically motivated cognitive tasks
J. Abnorm. Psychology
Spatial and object working memory impairments in schizophrenia patients: a Bayesian item-response theory analysis
J. Abnorm. Psychology
Theory of mind and schizophrenia
Neurocognitive dimensions characterising patients with first-episode psychosis
Br. J. Psychiatry
Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia
Arch. Gen. Psychiatry
Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia
Am. J. Psychiatry
Neurocognitive functioning in patients with schizophrenia: an overview
Working memory dysfunction in schizophrenia
J. Neuropsychiatry Clin. Neurosci.
Should schizophrenia be treated as a neurocognitive disorder?
Schizophr. Bull.
Backward masking in schizophrenia and mania: I. Specifying a mechanism
Arch. Gen. Psychiatry
Cited by (1036)
Associative learning and facial expression recognition in schizophrenic patients: Effects of social presence
2024, Schizophrenia Research: CognitionFunctional and structural connectivity correlates of semantic verbal fluency deficits in first-episode psychosis
2024, Journal of Psychiatric ResearchCorrelation analysis between insomnia symptoms and language function in patients with schizophrenia
2023, Schizophrenia Research: CognitionLessons Learned From Parsing Genetic Risk for Schizophrenia Into Biological Pathways
2023, Biological Psychiatry