Review
The global cognitive impairment in schizophrenia: Consistent over decades and around the world

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Abstract

Objective

Schizophrenia results in cognitive impairments as well as positive, negative, and disorganized symptomatology. The present study examines the extent to which these cognitive deficits are generalized across domains, potential moderator variables, and whether the pattern of cognitive findings reported in schizophrenia has remained consistent over time and across cultural and geographic variation.

Method

Relevant publications from 2006 to 2011 were identified through keyword searches in PubMed and an examination of reference lists. Studies were included if they (1) compared the cognitive performance of adult schizophrenia patients and healthy controls, (2) based schizophrenia diagnoses on contemporary diagnostic criteria, (3) reported information sufficient to permit effect size calculation, (4) were reported in English, and (5) reported data for neuropsychological tests falling into at least 3 distinct cognitive domains. A set of 100 non-overlapping studies was identified, and effect sizes (Hedge's g) were calculated for each cognitive variable.

Results

Consistent with earlier analyses, patients with schizophrenia scored significantly lower than controls across all cognitive tests and domains (grand mean effect size, g =  1.03). Patients showed somewhat larger impairments in the domains of processing speed (g =  1.25) and episodic memory (g =  1.23). Our results also showed few inconsistencies when grouped by geographic region.

Conclusions

The present study extends findings from 1980 to 2006 of a substantial, generalized cognitive impairment in schizophrenia, demonstrating that this finding has remained robust over time despite changes in assessment instruments and alterations in diagnostic criteria, and that it manifests similarly in different regions of the world despite linguistic and cultural differences.

Introduction

Schizophrenia is a “global” condition in many respects. It impacts widely-acting neurotransmitter systems (e.g. dopamine, glutamate, GABA) through subtle changes in brain microstructure, physiology, and connectivity, and these neurobiological differences give rise to a variety of affective, cognitive, and psychotic symptoms. Epidemiologically, the disorder cuts across cultures, regions, and genders, with an estimated lifetime prevalence of about 1% of the world's population. Functionally, schizophrenia is associated with considerable generalized disability, as affected individuals experience low rates of employment and marriage, decreased somatic health and quality of life, lower levels of educational achievement, and a marked decrease in life expectancy.

The effect that schizophrenia exerts on cognition can fairly be described as “global” as well. Resting on evidence from hundreds of studies and thousands of individuals, the finding that schizophrenia is associated with impairment across a wide range of higher-order cognitive performance domains is now well-established. Although some reviews highlight particularly large cognitive deficits in the domains of verbal episodic memory (Heinrichs and Zakzanis, 1998, Reichenberg and Harvey, 2007), executive functioning (Reichenberg and Harvey, 2007), or processing speed (Dickinson et al., 2007), the most consistent finding across studies has been an overall, generalized impairment across neuropsychological measures that persists in every clinical state and across patients' lifespans (Hyde et al., 1994, Albus et al., 2002, Hughes et al., 2003, Hill et al., 2004). The relationship of cognitive impairment in schizophrenia to symptom severity is modest (Hughes et al., 2003, Rund et al., 2004, Dominguez et al., 2009, Ventura et al., 2010). However, cognitive impairment shows consistent association with indexes of everyday functional capacity. Using a variety of cognitive assessment strategies, several studies have shown consistent associations between cognition and the UCSD Performance-based Skills Assessment, suggesting a high degree of criterion validity (Leifker et al., 2010). Cognitive variables are also widely used as intermediate phenotypes in genetic studies of schizophrenia, as attenuated cognitive deficits are seen even in the asymptomatic parents and siblings of schizophrenia patients (Dickinson et al., 2007), with some studies showing reduced impairment in more distant relatives (Tuulio-Henriksson et al., 2003, Glahn et al., 2007, Toulopoulou et al., 2007).

In 1998, Heinrichs and Zakzanis published the first large-scale meta-analysis of cognitive deficit findings in schizophrenia, drawing on more than 200 studies conducted between 1980 and 1997 (Heinrichs and Zakzanis, 1998) and documenting an overall mean impairment of 0.92 standard deviations relative to community comparison groups (Heinrichs, 2005). Various smaller reviews followed, generally focused on a particular cognitive domain (Aleman et al., 1999) or set of measures (Bokat and Goldberg, 2003). Although narrower in focus than the Heinrichs review, our 2007 meta-analysis (Dickinson et al., 2007) offered a general update for studies completed in the decade following Heinrichs and Zakzanis (1998) and reported a similar outcome. Across measures and samples, this later analysis found a grand mean effect size of schizophrenia on cognitive performance of 0.98 standard deviations.

The newest cohort of neuropsychological studies, however, differs from those sampled in previous meta-analyses in several ways. First, while Heinrichs and Zakzanis's (1998) seminal publication included samples of patients diagnosed according to DSM-III and DSM-III-R criteria, studies conducted within the past decade have virtually all defined schizophrenia according to criteria laid out in the DSM-IV and DSM-IV-TR. Second, since Heinrichs and Zakzanis's (1998) meta-analysis, several canonical neuropsychological measures have been revised (e.g. WAIS, WMS, CPT), and expert judgment regarding the most appropriate measures for the study of schizophrenia has evolved, resulting in the emergence of testing arrays like the MATRICS Consensus Cognitive Battery (⁎Kern et al., 2008, Nuechterlein et al., 2008). Finally, driven in part by the power requirements of genetics analyses, the most recent cohort of studies examining cognition in schizophrenia is uniquely international. The degree to which cognitive deficit findings in schizophrenia are similar across regions that differ substantially in both language and culture is unknown, however, and some performance differences have been reported across sites in different areas of the world (Harvey et al., 2003). As cognitive impairment is considered for inclusion as a possible specifier for psychotic disorders in ICD-11, the possibility of regional differences in neuropsychological measurement and/or performance is especially relevant.

A question in the field is whether decreased PubMed references to a “generalized deficit” in schizophrenia literature in recent years accurately reflect the reduced salience of generalized impairment for the field (Green et al., 2013). We believe the phenomenon remains of central relevance, hypothesizing that despite geographic dispersion of research samples as well as evolving assessment and diagnostic practices, evidence from recent years would show (1) broad impairment of cognitive performance in schizophrenia (2) a magnitude and pattern of impairment consistent with what was documented in earlier reviews, and (3) a similar magnitude and pattern of impairment in data from different geographic regions. We also investigated the effects of potential moderator variables on effect size, examining both clinical variables (e.g. medication, symptom ratings, chronicity of illness) and demographic variables (e.g. participants' sex, education).

Section snippets

Study and variable selection

Articles incorporated into this analysis were identified through a series of PubMed searches using combinations of key words schizophreni*, cogniti*, neurocogniti*, neuropsychologi*, executive function*, verbal, processing speed, psychomotor speed, perceptual speed, and attention. The searches were conducted for the period from January 2006 through June 2012. The year 2006 was selected as a start date because it represents the end of the period reviewed by the most recent meta-analysis of

Main meta-analysis

The results of the main meta-analysis are presented in Table 1. Across these studies, data were analyzed from 9048 patients with schizophrenia and 8814 healthy comparison subjects. Of our 100 studies, 96 reported the mean ages of both patients and controls. The sample weighted mean age for the schizophrenia group was 35.1 years (range of study means: 20.1 to 48.5) years, compared with 35.6 years for controls (range: 19.0 to 48.7 years). In the set of 91 studies reporting participant sex, 49.9% of

Discussion

The current analysis updates the evidence of broad cognitive impairment in schizophrenia, again revealing moderate to severe impairment in people with schizophrenia relative to controls across all neuropsychological measures studied, and somewhat larger cognitive differences in the domains of processing speed and episodic memory (see Fig. 1). These findings are quite consistent with earlier reviews. Remarkably, despite significant changes in diagnostic criteria, assessment materials and

Funding

This work was supported by the Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health (NIH), through funding to the Weinberger Lab, and the Lieber Institute for Brain Development, Baltimore, Maryland (http://www.libd.org).

Role of funding source

Support for this research was provided by the National Institute of Mental Health Intramural Research Program via direct funding to the Weinberger Lab. The authors of this manuscript report no competing interests.

Contributors

JS, EG, and DD collected and analyzed the data and prepared the first draft of the manuscript. All authors contributed to manuscript revisions.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgment

The authors would like to extend their heartfelt thanks to Jody Mozersky for her hard work on the meta-analysis article database.

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Support for this research was provided by the National Institute of Mental Health Intramural Research Program via direct funding to the Weinberger Lab. The authors of this manuscript report no competing interests.

1

Studies indicated with an asterisk were included in the main meta-analysis.

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