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Neuropsychological deficits in first-episode and chronic schizophrenia
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BIOL PSYCHIATRY 1995;37:593-683
REM latency (towards normal) without any changes in other sleep measures. In an effort to replicate these findings, we studied another nonoverlapping sample of 15 schizophrenic patients (SADS/RDC and DSM-IIiR). Polysomnographic studies were performed when patients were medication-free and after 3-4 weeks of neuroleptic treatment (with clinically determined doses of thiothixene or haloperidol). All sleep continuity measures (total sleep time, sleep latency, sleep efficiency) were improved after 3 weeks of neuroleptic treatment. REM latency increased (tended to normalize) with neuroleptie treatment, although seven of the 15 patients continued to exhibit short REM latencies (<60 minutes). REM activity and REM density did not change. Stage 3 sleep increased with neuroleptic treatment, although stage 4 sleep did not change; there was no significant increase in total slow-wave sleep (stage 3+4). These data replicate our previous findings and suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.
297. BIOLOGICAL PREDICTORS OF ONEYEAR OUTCOME IN SCHIZOPHRENIA
M. Goldman, R. Tandon, J.R. DeQuardo, S.F. Taylor, & J. Goodson
SATURDAY,, MAY 20
The purpose of the present study was to examine neuropsychological impairment in schizophrenia as a function of length of illness. We compared the neuropsychological performance of 25 first-episode (mean age - 28.7 years) with 53 chronic (mean age z 39.6 years) patients who had more than 2 years of illness; patients met SADS/RDC criteria for schizophrenia. The patient groups did not differ with respect to educational level, general levels of psychopathology (measured by BPRS), or the presence of positive and negative symptoms. The neuropsychological battery consisted of comprehensive assessment of attention, intellect, executive functioning, memory, motor functioning, and perceptual abilities. Individual task performance was referenced to normative based standard scores. The fmdings revealed that chronic patients demonstrated significantly more impairment on measures of performance IQ (p = 0.02), memory for both verbal (p = 0.05) and spatial information (p = 0.003) from the Wechsler Memory Scale, and measures of executive functioning including numbers of categories on the Wisconsin Card Sorting Test (p = 0.03) and Trailmaking, Part B (p = 0.01). Four of the five performance subtests (Block Design, Picture Arrangement, Object Assembly, and Digit Symbol) of the Wechsler Adult Intelligence Scale--Revised were significantly more impaired in the chronic patients (p = 0.008~3.07). The present study suggests that greater length of illness may result in deteriorative processes of some neuropsychological functions, particularly memory functioning, perceptual/organizational abilities, and those abilities thought to be subserved by the frontal lobes.
University o f Michigan Schizophrenia Program, Ann Arbor, MI 48109-0116 Outcomes in schizophrenia are heterogeneous. Because the identification of biological predictors of outcome may help explain the pathophysiologic mechanism underlying this heterogeneity, we conducted a prospective study to examine the impact of four biological variables associated with schizophrenia on 1-year outcome. The effect of gender on these associations was also investigated. The biologic variables, measured on 63 chronic meal-free RDC/DSM-III-R schizophrenic patients hospitalized at the University of Michigan (mean age: 28.1; males: 69%), were: ventricular size (VBR); rapid eye movement (REM) sleep latency, slow-wave sleep, and postdexamethasone cortisol nonsuppression (DST). Outcome was assessed along five dimensions (hospitalization, employment, social activity, psychopathology, and global functioning) using the Strauss-Carpenter scale 1 year after the index hospitalization. Data were analyzed by Pearson correlations. For the whole sample, short REM latency was significantly associated with poor outcome on all dimensions: hospitalization (p = 0.03), employment (p = 0.01 ), social activity (p = 0.05), psychopathology (,p = 0.01), and global functioning (p = 0.02). DST nonsuppression was associated with poor outcome on only one-dimension psychopathology (p = 0.05). Neither slow-wave sleep nor VBR was related to outcome. For data analyzed by sex, the correlations remained similar (and stronger in some cases) for females, but none of the biological variables were correlated with outcome in males. These results are consistent with a hypothesis that the mechanism underlying outcome heterogeneity in schizophrenia is sex-specific. The findings also underscore the importance of gender in understanding the biological basis of outcome heterogeneity in schizophrenia.
298. NEUROPSYCHOLOGICAL DEFICITS IN FIRST-EPISODE AND CHRONIC SCHIZOPHRENIA R.S. Goldman, I. Smet, R. Tandon, G. Lelli, L. Decker, S.F. Taylor, & S. Berent University o f Michigan Schizophrenia and Neuropsychology Programs, Ann Arbor, MI 48 109-0116
299. NEUROPSYCHOLOGICAL FUNCTION IN DEFICIT VERSUS NONDEFICIT SCHIZOPHRENIA I.C. Smet, R.S. Goldman, R. Tandon, L. Decker, G. Letli, S.F. Taylor, & S. Berent University o f Michigan Schizophrenia and Neuropsychology Programs, Ann Arbor, MI 48109-0116 Previous research has suggested that the presence of the deficit syndrome in schizophrenia implicates diminished responsivity to treatment and poor functional outcome. There is recent interest in determining the underlying extent of neuropsychological impairment in this syndrome. We compared the neuropsychological performance of 36 inpatients (mean age = 38.1 years) meeting criteria for the deficit syndrome (Schedule for the Deficit Syndrome) with 61 nondeficit inpatients (mean age = 32.3 years). Deficit syndrome patients had greater length of illness (p = 0.02), were significantly older (p = 0.05), and had expectedly greater levels of negative symptoms (p = 0.004), but the groups did not differ with respect to education, current intellectual functioning, or predicted premorbid intellectual status. Patients were given a comprehensive neuropsycho]ogical battery consisting of measures of attention, intellect, executive functioning, memory, motor functioning, and perceptual abilities. All examiners were blind to group status. Individual task performance was referenced to normative based standard scores. Both groups performed lower than the normative reference; however, deficit syndrome patients were found to demonstrate selectively greater levels of impaimlent on measures of frontal lobe functioning, including attentional flexibility (Trailmaking), concept formation (Wisconsin Card Sorting Test), verbal fluency (Controlled Oral Word Association Test), working memory (Digits Backwards), and social judgment (Comprehension from the Wechsler Adult Intelligence ScaleRevised)), motor speed (finger oscillation and reaction time), and verbal and visuospatial memory functioning (Wechsler Memory Scale). This impairment did not result from differences in general intellectual functioning. This study suggests that neuropsychological abnormalities, particularly in executive functions, may underlie the poor functional status of patients with the deficit syndrome.
BIOL PSYCHIATRY 1995;37:593-683
REM latency (towards normal) without any changes in other sleep measures. In an effort to replicate these findings, we studied another nonoverlapping sample of 15 schizophrenic patients (SADS/RDC and DSM-IIiR). Polysomnographic studies were performed when patients were medication-free and after 3-4 weeks of neuroleptic treatment (with clinically determined doses of thiothixene or haloperidol). All sleep continuity measures (total sleep time, sleep latency, sleep efficiency) were improved after 3 weeks of neuroleptic treatment. REM latency increased (tended to normalize) with neuroleptie treatment, although seven of the 15 patients continued to exhibit short REM latencies (<60 minutes). REM activity and REM density did not change. Stage 3 sleep increased with neuroleptic treatment, although stage 4 sleep did not change; there was no significant increase in total slow-wave sleep (stage 3+4). These data replicate our previous findings and suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.
297. BIOLOGICAL PREDICTORS OF ONEYEAR OUTCOME IN SCHIZOPHRENIA
M. Goldman, R. Tandon, J.R. DeQuardo, S.F. Taylor, & J. Goodson
SATURDAY,, MAY 20
The purpose of the present study was to examine neuropsychological impairment in schizophrenia as a function of length of illness. We compared the neuropsychological performance of 25 first-episode (mean age - 28.7 years) with 53 chronic (mean age z 39.6 years) patients who had more than 2 years of illness; patients met SADS/RDC criteria for schizophrenia. The patient groups did not differ with respect to educational level, general levels of psychopathology (measured by BPRS), or the presence of positive and negative symptoms. The neuropsychological battery consisted of comprehensive assessment of attention, intellect, executive functioning, memory, motor functioning, and perceptual abilities. Individual task performance was referenced to normative based standard scores. The fmdings revealed that chronic patients demonstrated significantly more impairment on measures of performance IQ (p = 0.02), memory for both verbal (p = 0.05) and spatial information (p = 0.003) from the Wechsler Memory Scale, and measures of executive functioning including numbers of categories on the Wisconsin Card Sorting Test (p = 0.03) and Trailmaking, Part B (p = 0.01). Four of the five performance subtests (Block Design, Picture Arrangement, Object Assembly, and Digit Symbol) of the Wechsler Adult Intelligence Scale--Revised were significantly more impaired in the chronic patients (p = 0.008~3.07). The present study suggests that greater length of illness may result in deteriorative processes of some neuropsychological functions, particularly memory functioning, perceptual/organizational abilities, and those abilities thought to be subserved by the frontal lobes.
University o f Michigan Schizophrenia Program, Ann Arbor, MI 48109-0116 Outcomes in schizophrenia are heterogeneous. Because the identification of biological predictors of outcome may help explain the pathophysiologic mechanism underlying this heterogeneity, we conducted a prospective study to examine the impact of four biological variables associated with schizophrenia on 1-year outcome. The effect of gender on these associations was also investigated. The biologic variables, measured on 63 chronic meal-free RDC/DSM-III-R schizophrenic patients hospitalized at the University of Michigan (mean age: 28.1; males: 69%), were: ventricular size (VBR); rapid eye movement (REM) sleep latency, slow-wave sleep, and postdexamethasone cortisol nonsuppression (DST). Outcome was assessed along five dimensions (hospitalization, employment, social activity, psychopathology, and global functioning) using the Strauss-Carpenter scale 1 year after the index hospitalization. Data were analyzed by Pearson correlations. For the whole sample, short REM latency was significantly associated with poor outcome on all dimensions: hospitalization (p = 0.03), employment (p = 0.01 ), social activity (p = 0.05), psychopathology (,p = 0.01), and global functioning (p = 0.02). DST nonsuppression was associated with poor outcome on only one-dimension psychopathology (p = 0.05). Neither slow-wave sleep nor VBR was related to outcome. For data analyzed by sex, the correlations remained similar (and stronger in some cases) for females, but none of the biological variables were correlated with outcome in males. These results are consistent with a hypothesis that the mechanism underlying outcome heterogeneity in schizophrenia is sex-specific. The findings also underscore the importance of gender in understanding the biological basis of outcome heterogeneity in schizophrenia.
298. NEUROPSYCHOLOGICAL DEFICITS IN FIRST-EPISODE AND CHRONIC SCHIZOPHRENIA R.S. Goldman, I. Smet, R. Tandon, G. Lelli, L. Decker, S.F. Taylor, & S. Berent University o f Michigan Schizophrenia and Neuropsychology Programs, Ann Arbor, MI 48 109-0116
299. NEUROPSYCHOLOGICAL FUNCTION IN DEFICIT VERSUS NONDEFICIT SCHIZOPHRENIA I.C. Smet, R.S. Goldman, R. Tandon, L. Decker, G. Letli, S.F. Taylor, & S. Berent University o f Michigan Schizophrenia and Neuropsychology Programs, Ann Arbor, MI 48109-0116 Previous research has suggested that the presence of the deficit syndrome in schizophrenia implicates diminished responsivity to treatment and poor functional outcome. There is recent interest in determining the underlying extent of neuropsychological impairment in this syndrome. We compared the neuropsychological performance of 36 inpatients (mean age = 38.1 years) meeting criteria for the deficit syndrome (Schedule for the Deficit Syndrome) with 61 nondeficit inpatients (mean age = 32.3 years). Deficit syndrome patients had greater length of illness (p = 0.02), were significantly older (p = 0.05), and had expectedly greater levels of negative symptoms (p = 0.004), but the groups did not differ with respect to education, current intellectual functioning, or predicted premorbid intellectual status. Patients were given a comprehensive neuropsycho]ogical battery consisting of measures of attention, intellect, executive functioning, memory, motor functioning, and perceptual abilities. All examiners were blind to group status. Individual task performance was referenced to normative based standard scores. Both groups performed lower than the normative reference; however, deficit syndrome patients were found to demonstrate selectively greater levels of impaimlent on measures of frontal lobe functioning, including attentional flexibility (Trailmaking), concept formation (Wisconsin Card Sorting Test), verbal fluency (Controlled Oral Word Association Test), working memory (Digits Backwards), and social judgment (Comprehension from the Wechsler Adult Intelligence ScaleRevised)), motor speed (finger oscillation and reaction time), and verbal and visuospatial memory functioning (Wechsler Memory Scale). This impairment did not result from differences in general intellectual functioning. This study suggests that neuropsychological abnormalities, particularly in executive functions, may underlie the poor functional status of patients with the deficit syndrome.