Josef Scherer

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.

Neurological soft signs and neuropsychological performance in patients with first episode schizophrenia.

Neurological soft signs and neuropsychological (NP) impairments are prevalent in schizophrenic patients. However, the relationship of these deficits is rarely studied, and it remains controversial in what way soft signs influence NP performance. The Neurological Evaluation Scale (NES) and a comprehensive neuropsychological test battery were used to assess soft signs and cognitive functions in 61 first-episode schizophrenic patients. The NP test battery included tests such as the California Verbal Learning Test, the Continuous Performance Test, the Span of Apprehension Test, the Stroop Color-Word Test, the Trail-Making Test and the Wisconsin Card Sorting Test. The NP tests were also administered to 87 healthy controls. The first-episode schizophrenic patients were split along the median of their NES total score (SS- vs. SS+). The level of NP performance and the differences in relative performance (shape of the NP profile) on NP functions between the two groups were assessed. The two groups (SS- vs. SS+) did not differ in any demographic or clinical variable. However, they differed in the level of their NP performance (profile mean) but did not show differential deficits in NP performance (profile shape). Neurologic soft signs influence NP performance and are correlated to a generalized NP deficit rather than to any specific NP functions.

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.

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.

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.

Panic disorder with or without concomitant depression 5 years after treatment: a prospective follow-up

50 patients with panic disorder (30 without and 20 with concomitant depression) were enrolled in a controlled treatment study using either imipramine or doxepin in addition to supportive psychotherapy and were then studied under naturalistic treatment conditions over a 5-year period. While patients with concomitant depression scored higher in overall measures of illness severity (as measured by HAMA, HAMD and GAS), no differences were detected between the groups with regard to panic disorder symptoms and degree of impairment. Our data suggest that comorbidity of panic disorder and depression is no prerequisite for poorer long-term outcome compared with panic disorder without depression.

Age at onset anticipation in familial schizophrenia. Does the phenomenon even exist

The discovery of dynamic mutations, like the expansion of unstable CG-rich trinucleotide repeat sequence mutations, has revived the interest in investigating the phenomenon of anticipation of age at onset of the illness (AAO) in familial schizophrenia. In those studies of parent-offspring pairs analyzed for AAO anticipation published to date, however, several ascertainment biases were not adequately controlled for. The present study focuses mainly on the age at investigation (AAI) bias, neglected so far, by investigating 96 schizophrenic parent offspring pairs and 26 aunt/uncle-niece/nephew pairs. When not controlling for a potential AAI bias, AAO differences in the parent-offspring sample in favor for anticipation were found in the same magnitude as reported by other authors (12.5 years, p < 0.0001). However, when controlling for AAI, these positive anticipation findings were compensated for (1.32 years, p=0.129). Additional selection procedures such as the exclusion of late-onset schizophrenia, the analysis of pairs where both members were through the age of risk, or the selection of aunt/uncle-niece/nephew pairs could not circumvent the AAI effect. These results suggest that the AAI effect is an essential bias in investigating anticipation, leading to false-positive AAO anticipation results if not taken into account.

Fluctuation of symptoms and social functioning in panic disorder with or without concomitant depression. A 5-year prospective follow-up.

After controlled treatment with either imipramine or doxepin with additional psychotherapy, 30 patients with pure panic disorder and 20 with concomitant depression were followed under ordinary treatment conditions over a 5-year period. While the overall level of illness severity was mild in both groups (slightly worse in the group with comorbidity), social impairment as well as fluctuation of symptoms were similar in both groups. Therefore, comorbidity of panic disorder and depression does not necessarily imply a poorer outcome in a self-referred patient sample initially treated with psychotropic drugs combined with supportive psychotherapy.

D2-dopamine-receptor occupancy during treatment with haloperidol decanoate.

We investigated in an open, explanatory study a total of 24 patients meeting DSM-III-R criteria for schizophrenia. Eighteen patients were treated for at least 4 weeks with a fixed dose of orally administered haloperidol for at least 4 weeks (mean daily dosage ranging from 0.07 to 0.35 mg/kg b.w.), and 6 patients received haloperidol decanoate with a fixed dose for at least 4 months (dosage range 50–150 mg/4 weeks; calculated mean daily dosage ranging from 0.02 to 0.09 mg/kg b.w.). One week after injection of haloperidol decanoate, the single photon emission computed tomography examination was performed. Our data suggest that D2-dopamine-receptor occupancy of 50 mg/4 weeks haloperidol decanoate 1 week after injection corresponds to an oral dose of 4.5 mg/day haloperidol.

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.