F. Mohr

Neurocognitive functioning in patients with first-episode schizophrenia : results of a prospective 5-year follow-up study.

To assess the course of neuropsychological (NP) impairment in schizophrenia, 71 patients with first episode (FE) schizophrenia and 71 healthy controls were given a comprehensive battery of NP tests at index assessment, after a 2-year and after a 5-year follow-up period. By means of the z-score standardization, summary scores for verbal intelligence (VBI), spatial organisation (SPT), verbal fluency (VBF), Verbal learning (VBL), semantic memory (SEM), visual memory (VIM), delay/retention rate (DEL), short-term memory (STM), visuomotor processing and attention (VSM) and abstraction/flexibility (ABS) were constructed. FE schizophrenia patients showed a worse performance compared to controls in all areas investigated, most pronounced in VSM, SEM and VBL. In the majority of cognitive domains, an improvement was found over the 5-year follow-up period without differences between the two groups. However, in VBF patients slightly deteriorated whilst controls improved and in memory functions patients improved less compared to controls. When controlling for relevant confounders, neither conventional nor atypical neuroleptics showed a deleterious influence on NP performance, except on VBF. Our data suggest that NP impairment is already present at the onset of the illness and remains stable over the early course of schizophrenia.

A prospective 2-year follow-up study of neurocognitive functioning in patients with first-episode schizophrenia.

Abstract. To investigate the temporal stability, or progressivity, of neuropsychological (NP) impairment in schizophrenia, 50 patients with first episode (FE) schizophrenia and 50 healthy controls were given a battery of tests at the outset of the study and after a two-year interval. Both patient and control groups were balanced with respect to age, gender, education and parental socioeconomic status. Summary rating scales for semantic memory (SEM), visual memory (VIM), verbal learning (VBL), visual-motor processing and attention (VSM) and abstraction/flexibility (ABS) were constructed. FE schizophrenics showed improvement in VBL, stability of function in SEM, VSM and ABS and absence of improvement in VIM. While performance in VSM and VIM is influenced by medication status, SEM seems to be trait-related and stable; VBL, however, seems to be state-related. Our data suggest that there is no proof for the assumption of progressive deterioration in NP functioning during the first few years of illness.

Are there gender differences in neuropsychological performance in patients with first-episode schizophrenia?

To investigate gender differences in neuropsychological (NP) functioning in first episode (FE) schizophrenia, consecutively recruited patients with FE schizophrenia (37 males, 29 females) and a subsample of these patients (20 males, 20 females), individually matched for gender, age, and education to healthy controls (20 males, 20 females) were compared on a battery of standardized neuropsychological tests. Women performed better than men in tests of verbal memory and learning, and men performed better than women in spatial organization. However, no differences were present between schizophrenic patients and controls, except that male and female schizophrenic patients showed the most pronounced impairment in visual motor processing, attention and verbal memory and learning. Our data suggest that gender does not appear markedly to modify the cognitive impairment characteristic of schizophrenia. However, they underline the necessity of controlling confounding factors on NP performance such as gender and education.

Motoric neurological soft signs and psychopathological symptoms in schizophrenic psychoses.

Motoric neurological soft signs (NSS) were investigated by means of the Brief Motor Scale (BMS) in 82 inpatients with DSM-III-R schizophrenic psychoses. To address potential fluctuations of psychopathological symptoms and extrapyramidal side effects, patients were examined in the subacute state, twice at an interval of 14 days on the average. NSS were significantly correlated with severity of illness, lower social functioning, and negative symptoms. Modest, but significant correlations were found between NSS and extrapyramidal side effects as assessed on the Simpson-Angus Scale. Neither the neuroleptic dose prescribed to the patient, nor scores for tardive dyskinesia and akathisia were significantly correlated with NSS. Moreover, NSS scores did not significantly differ between patients receiving clozapine and conventional neuroleptics. Patients in whom psychopathological symptoms remained stable or improved over the clinical course showed a significant reduction of NSS scores. This finding did not apply to those patients in whom psychopathological symptoms deteriorated. Our findings demonstrate that NSS in schizophrenic psychoses are relatively independent of neuroleptic side effects, but they are associated with the severity and persistence of psychopathological symptoms and with poor social functioning.

Neuropsychological impairment and psychopathology in first-episode schizophrenic patients related to the early course of illness

Abstract The objective of the present study was to explore whether the early course of illness including first onset of psychotic symptoms influences neuropsychological functioning and psychopathology in first-episode schizophrenics. Patients with a short prodromal period (n = 20) and patients with a long prodromal period (n = 20) and controls matched with regard to age, gender and education (n = 40) were administered a battery of standardized neuropsychological tests and psychopathological rating scales. The results indicate an overall difference in neuropsychological performance with the schizophrenic patients scoring lower than controls. Schizophrenic patients scored significantly lower in all subtests except in visual memory and abstraction/flexibility than controls. No significant difference between neuropsychological performance between patient samples was found. Psychopathology was more pronounced in the long prodromal period group rating higher on negative and affective symptoms compared with the short prodromal period group. The data suggests that neuropsychological deficits in first-episode schizophrenia are independent of the early course of schizophrenia, and although negative symptoms are associated with the length of the prodromal period, they do not imply greater neuropsychological impairment.

Smooth-pursuit eye movement dysfunction in schizophrenia: the role of attention and general psychomotor dysfunctions

Smooth-pursuit eye-tracking performance was examined in 100 schizophrenic patients and various control groups under both attention-enhancing and attentiondistracting conditions. The level of attentional demand was varied by introducing a secondary reaction time task that directed attention either toward or away from the visual-tracking target. Distraction from the target led to a significant deterioration of tracking performance in all subjects, which was most pronounced in the group of schizophrenic patients. Attention-enhancement, on the other hand, did not normalize performance in this group. In schizophrenic patients, mainly in the distraction condition, there was a moderate association between performance in tracking and tests presumably measuring prefrontal functions. Tracking accuracy from both conditions was related to general motor performance as measured by the Neurological Evaluation Scale. It was concluded that in schizophrenic patients attentional factors (distraction) may contribute to eye-tracking impairment, and that the impairment may be viewed as an aspect of general motor dysfunctions.

Neuropsychologische Defizite bei ersterkrankten schizophrenen Patienten Vergleich zu chronisch schizophrenen Patienten

ZusammenfassungMit einer umfangreichen neuropsychologischen Testbatterie wurden die kognitiven Leistungen, vor allem in den Bereichen der Gedächtnisfunktionen, der Sprache und der kognitiven Flexibilität/Abstraktionsfähigkeit, von 66 erstmals erkrankten Patienten aus dem schizophrenen Formenkreis, von 49 chronisch kranken schizophrenen Patienten sowie von 40 gesunden Kontrollpersonen erfaßt. Die drei Gruppen waren hinsichtlich Alter, Geschlecht und Schulbildung miteinander vergleichbar. Beide klinische Gruppen zeigen insgesamt signifikant schlechtere neuropsychologische Leistungen als die Kontrollgruppe. Das Leistungsprofil der erstmals stationär aufgenommenen Patienten weist ein Minimum im Bereich visomotorische Prozesse und Aufmerksamkeit (VSM) auf. Das gesamte Leistungsniveau dieser Gruppe liegt einerseits unter dem der gesunden Vergleichsgruppe, andererseits aber doch deutlich über dem der chronisch schizophrenen Patientengruppe. Vergleicht man die Leistungsprofile der beiden klinischen Gruppen, so zeigt sich bei den chronischen Patienten im Funktionsbereich VSM eine nochmals deutlichere Leistungseinbuße und darüber hinaus zusätzliche Defizite im Bereich Abstraktion/Flexibilität. Die vorliegenden Ergebnisse weisen auf eine grundlegende Beeinträchtigung neuropsychologisch erfaßbarer Funktionen bereits bei Erkrankungsbeginn hin, wobei die frontalen Dysfunktionen zugeschriebenen kognitiven Leistungen sich entweder im Krankheitsverlauf zunehmend verschlechtern oder Prädiktoren für einen ungünstigen Krankheitsverlauf sind. Diese Frage kann nur durch prospektive Verlaufsuntersuchungen beantwortet werden.SummaryBy administering an extensive battery of neuropsychological tests, cognitive performance of 66 patients with first episode schizophrenia, 49 patients with chronic schizophrenia and 40 healthy controls has been assessed in the areas of memory functions, speech and cognitive flexibility/ abstraction. The three groups were comparable with regard to age, gender and education. Both patient groups showed a significant generalized neuropsychological impairment relative to controls. Patients with first episode were most impaired in visual motor processing and attention (VSM). Besides impairment in VSM, performance in abstraction/flexibility was significantly worse in chronic schizophrenics compared to first episode schizophrenics. Our findings suggest that neuropsychological functions are already impaired at the onset of the illness. Whether cognitive impairment in performance that is attributed to frontal dysfunctions is deteriorating during the course of the illness or is predicting an unfavourable course can only be answered by prospective follow-up studies.

Electrodermal and vascular orienting response in schizophrenic patients: Relationship to symptoms and medication

Peripheral indicators of autonomic nervous system activity, including electrodermal activity and finger-pulse volume, were investigated in 100 schizophrenic inpatients. Healthy siblings of the patients and healthy subjects matched for age and gender served as control groups. Acoustic stimuli (70 dB) were presented and orienting response (OR) parameters were determined independently for the two response systems. The relationship of both OR measures to negative symptoms and medication was studied. The two OR measures were found to be not interrelated, i.e. most of the subjects were discordant with regard to presence or absence of their OR in the two different response systems. The electrodermal, but not the vascular OR. differed between patients and control groups. Among patients receiving medication with anticholinergic effects there were significantly more electrodermal nonresponders than among patients without such medication. There was no indication that electrodermal nonresponders show more negative symptoms or generally more severe psychopathology than electrodermal responders.

756 – The prevalence of acute extrapyramidal signs and symptoms in patients treated with clozapine, risperidone and conventional antipsychotics

BACKGROUND Acute extrapyramidal side effects (EPS) are a common phenomenon of treatment with conventional antipsychotics. Previous studies found that clozapine has little propensity to cause EPS, while risperidone produces some EPS, but at levels lower than those of conventional antipsychotics. METHOD We compared the prevalence and severity of EPS in patients treated with clozapine, risperidone, or conventional antipsychotics for at least 3 months. Our main hypothesis was that there would be differences between the three treatment groups with regard to akathisia, measured with the Barnes Akathisia Scale, and extrapyramidal motor side effects (rigidity, rigidity factor, tremor, salivation), measured with the Simpson-Angus scale. Secondarily, we were interested in possible differences between the three groups with respect to the anticholinergic comedication and the subjective impression of the patients, measured with the van Putten scale. RESULTS We studied 106 patients (41 patients treated with clozapine, 23 patients with risperidone, and 42 patients treated with conventional antipsychotics). The sample was 57.5% male and had a mean +/- SD age of 36.6 +/- 9.3 years. The mean dose of antipsychotics calculated in chlorpromazine equivalents was 425.6 +/- 197.1 mg/day in the clozapine group, 4.7 +/- 2.1 mg/day in the risperidone group, and 476.5 +/- 476.9 mg/day in the group treated with conventional antipsychotics. The point-prevalence of akathisia was 7.3% in the clozapine group, 13% in the risperidone group, and 23.8% in the group treated with conventional antipsychotics. The point-prevalence of rigidity and cogwheeling respectively was 4.9% and 2.4% in the clozapine group, 17.4% and 17.4% in the risperidone group, and 35.7% and 26.2% in the group treated with conventional antipsychotics. CONCLUSION Our results indicate that risperidone is superior to conventional neuroleptics in that it causes fewer EPS. In comparison to clozapine, risperidone produces EPS levels that are intermediate between clozapine and conventional antipsychotic drugs.

Neuropsychological (NP) functioning in first episode (FE) schizophrenia: A 2-year follow-up study

ION AND WORKING MEMORY IN SCHIZOPHRENIA including Raven’s Progressive Matrices and the Making Groups Test. A total of 23 schizophrenia patients from the MPRC Outpatient Research Program and 20 normal controls were studied. Patients demonstrated deficits on both simple storage and more complex forms of working memory (all p 0.46). The results suggest that the cause of the WM impairment in schizophrenia is at least 2-fold: (1) there are limitations on how much information can be held on line and (2) there are additional limitations in how much of this information can be used in the service of more complex D.C. Glahn, T.D. Cannon, R.E. Gur, J.D. Ragland, R.C. Gur Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA cognitive operations. Abstraction, the ability to use information to group stimuli in some meanineful wav. has lone been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients’ poor performance on the Wisconsin Card Sorting Test (WCST). However, patients’ deficits on the WCST may also be attributable to the working memory requirement of the test. In the current study, a new task was designed to investigate the relationship between abstraction and working memory in schizophrenia. The primary element of the task measures abstraction. In another condition, a working memory requirement is suuerimnosed on this module. A benefit of this naradigm MEMORY DYSFUNCTION IN FIRSTSEVERITY AND SELECTIVITY OFion, the ability to use information to group stimuli in some meanineful wav. has lone been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients’ poor performance on the Wisconsin Card Sorting Test (WCST). However, patients’ deficits on the WCST may also be attributable to the working memory requirement of the test. In the current study, a new task was designed to investigate the relationship between abstraction and working memory in schizophrenia. The primary element of the task measures abstraction. In another condition, a working memory requirement is suuerimnosed on this module. A benefit of this naradigm MEMORY DYSFUNCTION IN FIRSTSEVERITY AND SELECTIVITY OF EPISODE SCHIZOPHRENIA RX Goldman, J. Bates, R.M. Bilder, G. Reiter, J. Conley, E. Pappadopulos, M. Obuchowski, D. Robinson, J.M.A. Alvir, J. Lieberman, N. Schooler . _ . is that it can be used to determine whether deficits in working memory add to or multiply abstraction deficits in schizophrenia. In this study, patients with schizophrenia (n = 30) were Psychiatry Research, Hillside Hospital, PO Box 38, Glen Oaks, imnaired in their abstraction ability comnared with demogranhNew York 11004, USA icaily similar controls (n = 30); a working memory load affected patients’ abstraction performance, but to a degree equivalent to that seen in the controls. These findings suggest that a working memory load adds to, rather than interacts with, an abstraction deficit in determining patients’ performance on neuropsychological tests such as the WCST. WORKING MEMORY IN SCHIZOPHRENIA: IMPAIRMENTS IN STORAGE AND PROCESSING Neurocognitive studies in schizophrenia demonstrate generalized dysfunction, with relatively greater deficit in memory Using procedures for identifying amnesia in neurologic populafunction. Most studies however, have been conducted in tions (Squire 1986), patients were considered to have specifically patients of mixed chronicity and differing clinical states. We sought to determine the selectivity and severity of memory dysfunction, as well as its relationship to functional outcome, in first-episode patients (n = 88). Patients were evaluated while clinically stable (6 months following initial treatment), such that neurocognitive deficits are unconfounded with illness state. J.M. Gold, V.N. Iannone, C. Queern, R. W. Buchanan Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland21228. USA Patients with schizophrenia demonstrate impairments on a range of working memory (WM) tests. We explored: (1) whether these impairments involve both simple storage capacity (forward span) and more complex WM functions (Letter-number sequencing, Alphabet Recoding); (2) whether patient-normal control differences on complex WM tasks are mediated by simple storage deficits; and (3) the relationship of simple and complex WM tasks to fluid reasoning measures, severe memory disturbance if their memory performance was 15 points below their Full Scale IQ, as well as 2 standard deviations below normal. Using this conservative criterion, 28% of clinically stable patients demonstrated severe memory dysfunction. This is a large percentage considering the relative youth of the sample (25.7 k 6.3 years). We then determined the extent to which memory dysfunction is predictive of longerterm social vocational outcome (Social Adjustment Scale). Severe memory impairment impacted most negatively on general adjustment outcome (t (62) =2.1, p ~0.05). The present study suggests that schizophrenia results in severe memory dysfunction in almost one third of new-onset cases despite successful treatment, and this impairment deleteriously impacts functional outcome.