1. ¹Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
2. ²Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA
3. ³Department of Psychology, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA
4. ⁴Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
5. ⁵Quintiles Inc., Morrisville, NC, USA
6. ⁶Department of Psychiatry, University of California, San Diego, CA, USA
7. ⁷Maryland Psychiatry Research Center, Baltimore, MD, USA
8. ⁸Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA
9. ⁹Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
10. ¹⁰Psychiatry Service, New Mexico VA Health Care System and Department of Psychiatry, University of New Mexico, Albuquerque, NM, USA
11. ¹¹Clinical Insights, Glen Burnie, MD, USA
12. ¹²Corrigan Mental Health Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA
13. ¹³Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
14. ¹⁴Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
15. ¹⁵Department of Biological Psychiatry, John Umstead Hospital, Duke University Medical Center, Durham, NC, USA
16. ¹⁶Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York State Psychiatric Institute, New York, NY, USA

Correspondence: Dr RSE Keefe, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3270, Durham, NC 27710, USA, Tel: +919 684 4306, Fax: +919 684 2632, E-mail: richard.keefe@duke.edu

Received 17 October 2005; Revised 11 January 2006; Accepted 21 February 2006; Published online 19 April 2006.

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=0.13–0.27), but correlations with positive symptom severity were near zero (r<0.08). 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.