CNS Spectr. 2005;10(4):277-280
Dr. Kurtz is neuropsychologist in the Schizophrenia Rehabilitation Program at the Institute of Living, in Hartford, Connecticut, and assistant professor of psychiatry in the Department of Psychiatry at Yale School of Medicine in New Haven, Connecticut. Dr. Seltzer is senior consultant for Schizophrenia Services at the Institute of Living. Ms. Ferrand is research assistant in the Schizophrenia Rehabilitation Program at the Institute of Living. Dr. Wexler is professor of psychiatry in the Department of Psychiatry at Yale School of Medicine.
Disclosures: This work was supported in part by a grant from Research Free Funds from Hartford Hospital, grant R03 MH-65377 from the National Institutes of Mental Health (NIMH), a NARSAD Young Investigator Award to Dr. Kurtz, grant K02 MH-001296 from the NIMH to Dr. Wexler, and gifts from the Spencer T. and Ann W. Olin Foundation to the Institute of Living, Hartford Hospital’s Mental Health Network. This article was submitted on March 22, 2004, and accepted on August 28, 2004.
Please direct all correspondence to: Matthew M. Kurtz, PhD, Schizophrenia Rehabilitation Program, Fuller 1, Institute of Living, 200 Retreat Avenue, Hartford, CT 06106; E-mail: firstname.lastname@example.org.
- Patients with schizophrenia show deficits in neurocognitive function in a variety of domains relative to healthy controls.
- There is support that intellectual function is stable in young to middle-aged outpatients with schizophrenia over a follow-up interval of 5–10 years.
- With the exception of speeded motor sequencing, there is little evidence in the current study for a decline in intelligence quotient, executive function, attention, verbal learning, and non-verbal memory in outpatients with schizophrenia over a 10-year follow-up period.
Introduction: A wealth of evidence indicates that neurocognitive deficits are evident in patients with schizophrenia at both illness onset and after many years of treatment. Little is known regarding if or how these deficits change during the lifespan. The goal of the study was to evaluate changes in full-scale intelligence quotient and neurocognitive test performance over a 10-year interval in patients with schizophrenia.
Methods: Twelve patients were administered the Wechsler Adult Intelligence Scale-Revised as a measure of intellectual function and a neuropsycshological test battery including measures of attention, verbal and non-verbal memory, language, visuospatial function, problem-solving, and motor function at entry to the study and at a 10-year follow-up.
Results: With the exception of performance on a measure of speeded motor sequencing, there was no significant decline in any of the measures at 10-year follow-up. Results from a measure of sustained auditory attention showed improvement at follow-up.
Discussion: These data support a neurodevelopmental model of schizophrenia for young adult to middle-age patients by suggesting that neurocognitive deficits that emerge either before disease onset or early in the course of the illness remain stable as the patient ages.
Conclusion: Overall, measures of intelligence quotient as well as specific neurocognitive skills, do not decline over a 10-year period in at least a subgroup of patients with schizophrenia.
From its earliest conceptualizations, schizophrenia has often been viewed as a neurodegenerative disorder characterized by progressive worsening of clinical symptoms, neurocognitive function, and psychosocial status.1 Consistent with this model, cross-sectional studies2 of patients with schizophrenia have provided evidence that measures of executive-function show selective worsening across a 40-year period that is beyond that associated with the aging process in healthy people. In contrast, several longitudinal studies have found that most cognitive skills, including measures of intelligence quotient (IQ), executive function, attention, verbal and non-verbal memory, language, spatial ability, and sensory motor skill are remarkably stable over time when measured at a brief 1–2-year test-retest interval every3-5 or at a longer 5-year interval.3,6-8 Indeed, several longitudinal studies6,8-10 have reported modest improvement in performance on overall measures of IQ and specific neurocognitive measures. Discrepancy between these findings may reflect methodological limitations of cross-sectional designs, such as “cohort” effects, or may relate to the brief test-retest interval employed in longitudinal studies to date. To help resolve these differences we investigated the trajectory of neurocognitive deficits in patients over a 10-year follow-up interval.
Twelve participants with a diagnosis of schizophrenia by the Structured Clinical Interview for Diangostic Manual of Mental Disorders, Third Edition, Revised11 were studied. History of neurological illness or trauma, mental retardation, or substance abuse at time of assessment was exclusion criteria. Mean age at first assessment was 29.9 years, (SD=5.9; range=19–38). Participants had a mean 13.4 years (SD=2.1; range: 12–18) of education and had been ill for an average of 8 years (SD=5.2; range: 2–19). Mean test-retest interval was 10.2 years (SD=1.5; range: 8.4–12.2). All patients were stabilized on neuroleptic medication both at study entry and at retest. At index assessment, 67% of patients were treated with typical antipsychotic medication and 33% were treated with clozaril. At follow-up, all patients were treated with ≥1 atypical antipsychotic, while 17% of patients were treated with atypical antipsychotic as well. The sample was 83% Caucasian and 17% African American. At the index assessment, 67% of the sample was employed or a student at least part-time, while at follow-up 25% of the sample was employed or a student at least part-time. Twenty-five percent of the sample was involved in volunteer work at follow-up. Those retested represented 24% of the 49 patients initially assessed.12 Contact information for possible participants was obtained via public records using Lexis-Nexis People Finder Libraries. This yielded reliable phone numbers as well as home address information for 19 patients and address information only for 13 patients. Seventeen of the 19 patients with phone numbers were contacted successfully (one patient was excluded before contact for history of repeated violence and one had committed suicide). Of these, 12 agreed to be retested. Community visits to a subset of the 17 patients with home address information only did not yield any additional participants.
Patients were assessed at both time points with the Auditory Attention Task,13 Verbal Fluency Test,14 Grooved Pegboard,15 Hidden Figures Test,16 Rey Auditory Verbal Learning Test,17 Rey Osterreith Complex Figure Test (RCFT),18 Trailmaking Test,19 Wechsler Adult Intelligence Scale-Revised (WAIS-R),20 and the Wisconsin Card Sorting Test.21 Where published relevant normative data were available, raw neuropsychological test scores were corrected for age, education, and gender (ie, Trailmaking Test, Grooved Pegboard, and Wisconsin Card Sorting Test22) age, gender, education, and race (Verbal Fluency Test)23 or age (Rey Auditory Verbal Learning Test),24 and RCFT.18 Paired t-tests were conducted to assess significant changes in cognitive test performance from index assessment to follow-up. To assess the degree of test-retest stability for each cognitive measure intraclass correlation coefficients were also computed for variables between the two time points. Where data was non-normally distributed Wilcoxon signed-rank tests were substituted as a non-parametric equivalent of a paired t-test for data collected at two time points from the same participant. In no cases did results of the Wilcoxon signed-rank test differ from t-test results, thus parametric tests are reported for all measures. All statistical tests were two-tailed. Alpha was set at .05 for all analyses.
With the exception of slower performance on a measure of speeded motor sequencing, the Grooved Pegboard test, at the 10-year follow-up (P<.05) there was no significant decline in any measure across the 10-year interval (Table). Intraclass correlation coefficients for verbal, performance, and full-scale IQ measures were 0.81, 0.93, and 0.88, respectively. Measures of executive function, verbal learning, non-verbal memory, and language were not significantly different at follow-up. Mean total correct improved for the Auditory Attention Test, a sustained attention test. Differences between recruited patients and those lost to follow-up on age, education, age of disease onset, number of hospitalizations, IQ, and total symptom score variables at entry to the protocol were not significant (all P>.38).
With the exception of speeded motor sequencing, the obtained results indicate there was no cognitive deterioration in the 10-year interval in young adult patients with schizophrenia. Verbal, performance, and full-scale IQ were highly stable. In addition, performance on measures of auditory sustained attention showed some evidence of improvement. This is only the second study, to our knowledge, to assess neurocognitive skills, longitudinally across a 10-year follow-up period in schizophrenia patients. Our results combined with other, larger data sets1,4-5 utilizing similar measures and relatively long test-retest intervals provide support for a neurodevelopmental rather than a neurodegenerative model of cognitive deficits in schizophrenia for young adult to middle-aged patients.
Our findings are generally consistent with those of Stirling and colleagues25 with a few exceptions. In that study, a sample of 24 patients with schizophrenia was assessed with four subtests from the Performance subscale of the WAIS-R and an abbreviated neuropsychological test battery at 10-year follow-up. No deterioration was evident on measures of executive function, verbal and face memory, visuospatial function, and language. In contrast to the current findings, significant deterioration was evident on the Object Assembly and Picture Completion subtests from the WAIS-R, and a measure of non-verbal memory. Differences in obtained results may reflect differences in sample composition: the Stirling and colleagues25 study included only first-episode patients. Caveats for the current study include the small sample size. However, with the exception of the RCFT delayed memory condition, effect sizes for measures with a decrement in mean performance over the 10 years were close to/below Cohen’s cut-off criteria for a significant effect size.26 Thus, even with larger sample sizes, effect sizes of this magnitude would be unlikely to be detected. For example, the mean decrement on the copy condition of the RCFT, with one of the largest obtained effect sizes of 0.23, would only be detected 60% of the time with a sample size of 187 subjects (α=.05, two-tailed). Thus, we conclude that the absence of significant cognitive decline is unlikely to be an artifact of limited sample size. Second, the retest sample may have represented a “good outcome” subtype of the disease as indicated by their stable address and/or phone number. Nonetheless, at least at study entry, patients lost to follow-up did not differ from re-assessed patients on demographic, clinical, or cognitive variables. Third, levels of attained education (13.4 years) and mean IQ suggest that the sample as a whole was higher-functioning and may not be representative of those patients with a more deleterious course of illness. Fourth, while patients were generally in a relatively early phase of their illness, three patients in the sample had been ill for >10 years at study entry. Future research should investigate the trajectory of neurocognitive deficits over similarly long test-retest intervals in patients stratified according to their duration of illness.
Taken together, results from this study showed that, with the exception of a measure of speeded motor sequencing, overall measures of IQ and specific neurocognitive skills did not deteriorate over a 10-year test-retest interval in a sample of patients with schizophrenia. These data support a neurodevelopmental model of schizophrenia for young adult to middle-age patients by suggesting that neurocognitive deficits that emerge either before diagnosis or early in the course of the illness remain stable as the patient ages.
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