Baseline Neurocognitive Deficits in the CATIE Schizophrenia Trial

Abstract

Neurocognition is moderately to severely impaired in patients with schizophrenia. However, the factor structure of the various neurocognitive deficits, the relationship with symptoms and other variables, and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia. An 'all-comer' approach to cognition is needed, as provided by the baseline assessment of an unprecedented number of patients in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial. From academic sites and treatment providers representative of the community, 1493 patients with chronic schizophrenia were entered into the study, including those with medical comorbidity and substance abuse. Eleven neurocognitive tests were administered, resulting in 24 individual scores reduced to nine neurocognitive outcome measures, five domain scores and a composite score. Despite minimal screening procedures, 91.2% of patients provided meaningful neurocognitive data. Exploratory principal components analysis yielded one factor accounting for 45% of the test variance. Confirmatory factor analysis showed that a single-factor model comprised of five domain scores was the best fit. The correlations among the factors were medium to high, and scores on individual factors were very highly correlated with the single composite score. Neurocognitive deficits were modestly correlated with negative symptom severity (r ¼ 0.13-0.27), but correlations with positive symptom severity were near zero (ro0.08). Even in an 'all-comer' clinical trial, neurocognitive deficits can be assessed in the overwhelming majority of patients, and the severity of impairment is similar to meta-analytic estimates. Multiple analyses suggested that a broad cognitive deficit characterizes this sample. These deficits are modestly related to negative symptoms and essentially independent of positive symptom severity.

Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia

“…Additionally, despite extracting a three-factor solution from a lengthy neuropsychological battery, Green and colleagues argued that a large reliable general factor (accounting for 45% of total variance) justified combining all variables into a single composite to evaluate pharmacological treatment effects (Green et al, 2002). In a confirmatory factor analysis of cognitive data from the CATIE study (1332 schizophrenia spectrum patients), unitary and multifactor models were directly compared and a single-factor model provided a better fit than a five-factor model (Keefe et al, 2006). A principal components analysis of these data also supported a unitary factor, with just one component exceeding 1.0 eigens (Keefe et al, 2006).…”

“…The CATIE battery was the primary cognitive measure. This battery requires approximately 90 min to administer 10 tests that characterize six neuropsychological domains (see Keefe et al, 2003Keefe et al, , 2006. The BACS can be administered in 35 min and consists of six tests covering four domains (Keefe et al, 2004 (Keefe et al, 2004).…”

“…In a confirmatory factor analysis of cognitive data from the CATIE study (1332 schizophrenia spectrum patients), unitary and multifactor models were directly compared and a single-factor model provided a better fit than a five-factor model (Keefe et al, 2006). A principal components analysis of these data also supported a unitary factor, with just one component exceeding 1.0 eigens (Keefe et al, 2006). Similarly, a hierarchical model representing a broad cognitive dimension, rather than a multifactor model of separate latent cognitive factors, was a better fit for performance on individual tests in chronic schizophrenia (Dickinson et al, 2006).…”

“…One of these, the Brief Assessment of Cognition in Schizophrenia (BACS: Keefe et al, 2004), requires less than 35 min to administer and has an excellent completion rate and high reliability (Keefe et al, 2004). A second battery was developed and used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project (Keefe et al, 2006). This was the first large community trial designed to evaluate the comparative effectiveness of different antipsychotic treatments for schizophrenia (Keefe et al, 2003).…”

Toward a Neuro-Cognitive Animal Model of the Cognitive Symptoms of Schizophrenia: Disruption of Cortical Cholinergic Neurotransmission Following Repeated Amphetamine Exposure in Attentional Task-Performing, but Not Non-Performing, Rats

“…Based on the fundamental role of attentional processes for learning and general cognitive control, attentional dysfunctions have been considered a central and even essential characteristic of schizophrenia (Braff, 1993;Braff and Light, 2004;Braver et al, 1999;Keefe et al, 2006;McGhie and Chapman, 1961;Nuechterlein et al, 1994;Venables, 1964).…”