12. Psychology, cognitive

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12. Psychology, Cognitive WORKING MEMORY DETERMINES SENTENCE LENGTH IN SCHIZOPHRENIA: TESTING THE PREDICTIONS OF A CONNECTIONIST MODEL L.P. Aakerlund, R. Hemmingsen, A.L. Madsen, A.M. Holm, H. 0rum Department Bispebjerg

of Psychiatry, Bispebjerg Bakke 23,2400-Copenhagen

University Hospital, NV, Denmark

Working memory (WM) denotes the ability to hold information online for moment-to-moment usage. Schizophrenic patients have been shown to have impaired WM. Various language disturbances are well known in schizophrenia. Until now, few theories have provided an explanatory link between these observations. We present a computed artificial neural network model of normal language understanding and production. A lesion of the models WM had the following consequences: the processing of shorter sentences was unaffected, whereas longer sentences were characteristically impaired. We predicted: (1) schizophrenic patients should produce shorter sentences than normal subjects, and (2) the mean number of words per sentence in spontaneous schizophrenic language should correlate with WM capacity. We analyzed spontaneous language and WM capacity, measured by the Wisconsin Card Sorting Test in normal subjects (n = 17) and schizophrenic subjects (n = 28). Prediction (1) was confirmed withp < 0.0001, and prediction (2) withp < 0.001 andp < 0.03, for two different measures of WM. We conclude that WM restricts the length of sentences schizophrenic patients can understand and produce. This has implications for future research on how various languageand thought-disturbances in schizophrenia may be the result of dysfunctional working memory.

NEUROCOGNITION A LONGITUDINAL

IN EARLY PSYCHOSIS: STUDY

J. Addington, D. Addington Department of Psychiatry, Alberta T2N 2T9, Canada

University

of Calgary,

Calgary,

Neurocognitive deficits are a core feature of schizophrenia. It has been suggested that individuals experiencing their first episode of schizophrenia are already exhibiting neurocognitive deficits. Although these patients may not evidence as severe impairment as those who have experienced multi-episodes of schizophrenia, they have more impairment relative to nonpsychiatric controls. This is an ongoing longitudinal study comparing the neurocognitive functioning of 88 individuals who had recently been diagnosed with schizophrenia or schizophreniform disorder (FE) with 76 individuals with a diagnosis of schizophrenia, who had been ill for many years (ME). Measures

included the PANS& visual and verbal memory, early information processing, sustained attention, and executive functioning. Of the first-episode sample, 55 were reassessed 1 year later. The ME group had more negative symptoms (p < 0.05) and performed more poorly on executive functioning tasks (p i 0.01). The groups did not differ on the other cognitive tasks. Neurocognitive functioning was associated with negative symptoms but not with positive symptoms in both groups, At l-year follow-up the FE group demonstrated significant improvement in verbal memory (p < O.Ol), visual attention (p < O.Ol), early information processing (p < 0.05), and executive functioning @ < 0.05). These results suggest that FE subjects have early signs of neurocognitive impairment that improves over time.

RISPERIDONE ADVERSELY AFFECTS WORKING MEMORY IN THE RAT C. Anderson, C.P. Lawler, R.B. Mailman, J.A. Lieberman UNC Neuroscience University of North

Center and Department Carolina, Chapel Hill,

of Psychiatry, NC27599. USA

Cognitive impairment is now accepted as one of the major disabilities associated with schizophrenia, affecting 40 to 60% of schizophrenics. The intent of the work presented here was to determine the effect of antipsychotic drugs currently in use on working memory, a crucial aspect of comprehension, reasoning, and planning that allows information to be stored briefly and later processed and manipulated. Three antipsychotic drugs were orally administered to adult, male Sprague-Dawley rats in their drinking water: haloperidol(l.0 mg/kg/day), clozapine (20 mg/kg/day), and risperidone (1 mg/kg/day). A vehiclecontrol group was also included. Drug treatment was for 4 or 8 months, with an N of 25 rats per drug group. Animals in each drug group were divided into two Radial Arm Maze (RAM) experiments. In Experiment 1, animals received one month of drug administration and then underwent training on the RAM. In Experiment 2, drug-naive animals underwent training in the RAM prior to receiving any drug treatment. Once these animals reached proficiency with the task, they were randomly placed in a drug group. They were re-tested on the RAM 6 months later. The results indicate that in Experiment 1, a significant number of working-memory errors, or the number of repeated visits to the same arm, were made by the risperidone group. There were no significant differences between the three drug groups and vehicle with regard to choice accuracy; i.e., the number of correct responses prior to the first error, although the animals in the risperidone group showed a trend to make the tirst error earlier than the other three drug conditions. In Experiment 2, the animals in the risperidone group made a significantly greater number of working-memory errors over the 10 retest trials than animals in either the clozapine or haloperidol groups, or vehicle. The errors were particularly notable during the first 4 days of the retest sessions. Again, there were no significant differences between the four drug groups with regard to choice accuracy. In conclusion, it

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is clear that animals exposed to risperidone for 4 or 8 months exhibit a significant number of working-memory errors when compared to animals exposed to either clozapine or haloperidol, or vehicle. These results may help to elucidate possible effects for adversely affecting working memory in schizophrenic patients.

USING SENTENCE CONTEXTS TO STUDY SCHIZOPHRENIA: REGIONAL SPECIFICITY OF CLOZE PROBABILITIES S.M. Arcuri, S. Rabe-Hesketh, R.G. Morris, P.K. McGuire Department of Psychological De Crespigny Pk. London,

Medicine, Institute SES SAF. UK

of Psychiatry,

Sentence contexts (SC: stems of sentences from which the final word has been omitted) are a valuable tool in studying linguistic processing in schizophrenia (Niznikiwicz et al., 1997). A key feature of a SC is its Cloze probability (CP: proportion of subjects using a word to complete a SC). Published CPs have been defined for a population of North American students (Bloom and Fischler, -1980). Because we wanted to study linguistic processing in patients with schizophrenia from inner London, we sought to define CPs for sentences in local volunteers. One hundred and sixty incomplete SCs were presented to 73 volunteers. The frequencies of words used to complete the sentences appropriately were computed as the CP for each context. We then compared the CPs from our sample with those from Bloom and Fischler. Only SCs with higher CPs were compared. There were significant differences in CPs from the two samples in 15.3% of the SCs analyzed (p = 0.01). Such differences are much higher than expected by chance and probably reflect demographic and cultural differences in the composition of the samples. When employing SCs to study linguistic processing, it is advisable to normalise the stimuli in the same population as that to be studied.

A COGNITIVE-BEHAVIORAL APPROACH FOR THE TREATMENT OF PANIC IN SCHIZOPHRENIA P.B. Arlow, P.C. Bermanzohn, Y.M. Pratt, S. Pollack, S.G. Siris Hillside Hospital/Queens Day Center, 87-80 Boulevard, Jamaica, New York 11432. USA

Merrick

Background: Over 25% of schizophrenic patients are estimated to have panic attacks, yet cognitive-behavioral therapy (CBT) as an adjunct to antipsychotic medications remains largely unexplored in this patient group, even though its use holds theoretical interest and clinical relevance. Therefore, we

designed a study to evaluate the effectiveness of CBT in a group of patients with chronic schizophrenia and panic disorder. Method: Sixteen subjects participated in a nonrandom allocation controlled trial in which the first 8 subjects referred received 12 weeks of group CBT, and the next 8 subjects were given treatment as usual. Evaluations for panic, psychosis, quality of life and other measures were done at baseline, posttreatment, and 9 months from baseline. Results: Qualitatively, there was more improvement in the CBT-treated patients, but overall score differences in this small sample fell short of statistical significance. A correlation was found between ratings of panic and paranoia in this study. Conclusions: Many persons with chronic schizophrenia and panic may be able to utilize cognitive-behavioral therapy, but research with larger samples is necessary to establish efficacy. The authors will offer observations and suggestions for designing CBT interventions for future studies of panic and schizophrenia. For example, treatment for longer periods (6 months to 1 year) or ‘booster’ sessions are possibilities. The authors will also discuss modifications for CBT use in general for schizophrenia.

THE ROLE OF WORKING MEMORY IN LANGUAGE PRODUCTION AND ITS DISTURBANCE IN SCHIZOPHRENIA D.M. Barth Department of Psychology, 112.5, One Brookings Drive,

Washington University, Campus Box St Louis, Missouri 63130, USA

A novel experimental paradigm was developed to examine the role of working memory (WM) in language production, and the role that WM dysfunction may play in language disturbances in schizophrenia. Although numerous lines of research support links between disturbances in prefrontal cortex and WM in schizophrenia, it is not yet clear how these deficits relate to schizophrenic symptoms such as language disturbances. The paradigm was specifically designed to examine the role of WM in one component of language production: the on-line production of anaphoric references. The WM conditions of the task proved the ability to maintain prior discourse information over a delay, both with and without interference. The results of these studies are consistent with the hypothesis that individuals maintain prior discourse information in WM during ongoing language production, and suggest that the presentation of irrelevant information can disrupt the ability to maintain such discourse representations. Further, the results suggest that patients with schizophrenia suffer from a disturbance in the ability to use prior discourse information to overcome prepotent, but inappropriate, productions in speech. However, this deficit appears to be present among schizophrenia patients even when prior information does not need to be held in memory over a delay.

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WAIS-III SHORT FORMS FOR USE IN SCHIZOPHRENIA RESEARCH C.R.

Blyler,

V.N.

Iannone,

J.M.

Gold,

R.W.

Buchanan

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, Maryland21228. USA The recent publication of the third version of the WAIS, the standard test of intelligence, requires the development of a new short form for use with schizophrenic patients for many clinical and research purposes. We used regression analyses of complete WAIS-III data on 41 schizophrenic outpatients and 41 education-, gender-, and age-matched healthy subjects to determine the best combination of subtests to use as a short form. Excluding 3 subtests that are time-consuming to administer and/or difficult to score for schizophrenic patients, and requiring that the solution include 1 subtest from each of the 4 WAIS index scores, the combination that most fully accounted for the variance in full scale IQ (FISQ) for both schizophrenic patients (r’ = 0.90) and healthy controls (r* = 0.86) included Information, Block Design, Arithmetic, and Digit Symbol Coding. When the restriction regarding index scores was relaxed, the best-4 subtest solution included Information, Block Design, Arithmetic, and Similarities and explained 93% of the variance in FSI for schizophrenic patients and 91% for healthy controls. We recommend these short forms for use in future research and clinical practice in which a quick, accurate IQ estimate is desired.

EXAMINATION OF MAGNOCELLUAR AND PARVOCELLULAR VISUAL PATHWAY FUNCTION IN SCHIZOPHRENIA USING ELECTROPHYSIOLOGICAL AND PSYCHOPHYSICAL TECHNIQUES P.D. J.M. S.G. D.C.

Butler, I. Schechter, Harkavy-Friedman, Schwartz, J. Gordon, Javitt

L.A. DeSanti, J. Maddox, V.C. Greenstein, V. Zemon, J.M. Gorman,

Nathan Kline Institute, I40 Old Orangeburg New York 10962, USA

Road,

Orangeburg,

Deficits in visual backward masking (VBM) in patients with schizophrenia (SCZ) may be attributable to impaired interactions between magnocellular (M) and parvocellular (P) visual systems. For the present study, integrity of processing within these systems was analyzed using visual evoked potentials (VEPs), along with psychophysical VBM functions. Fifty three patients with schizophrenia or schizoaffective disorder and 52 controls participated. Integrity of the M system was evaluated using low-luminance contrast and low-spatial frequency (LSF) achromatic stimuli, while integrity of the P system was evaluated using high-luminance contrast and high-spatial frequency (HSF) achromatic stimuli and by examining chromatic con-

trast. No deficits were observed to achromatic M or P stimuli alone, although suggestive abnormalities in chromatic P processing were observed. In VBM studies. deficits were seen to both LSF and HSF masks, indicative of a deficit in both M and P pathways. Thus, VBM studies indicate that interactions between M and P pathways may be aberrant in patients with schizophrenia, while lower level processing, as measured by the VEPs, may be fairly intact. Future studies will further explore the nature of M and P pathway interactions in patients with schizophrenia. (Supported by NIMH R03 MH51914 and a VA Merit Review Grant.)

INTERMITTENT D, AGONIST COADMINISTRATION REVERSES CHRONIC HALOPERIDOL-INDUCED WORKING MEMORY DEFICITS IN YOUNG MONKEYS: THERAPEUTIC IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA S.A. Castner, P.S.

G.V. Goldman-Rakic

Williams,

T.A.

Trakht,

Section of Neurobiology. Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA While effectively treating positive symptoms of schizophrenia, chronic haloperidol fails to improve and may even exacerbate cognitive deficits and negative symptoms of the disease. In rhesus monkeys, chronic haloperidol treatment induces a downregulation of D, dopamine receptors in the prefrontal cortex. Optimal level of dopamine stimulation of D, receptors in the cortex is required for successful performance on working memory tasks. The present experiment was designed to determine if chronic haloperidol administration impairs working memory, and whether or not this deficit can be reversed by intermittent coadministration of a selective D, dopamine receptor agonist. Monkeys were trained on spatial and object working memory tasks. After a consistent level of approximately 75% performance was established, haloperidol was administered bid (0.07-0.20 mg/kg/d), and animals were tested 3-5 days per week. After exhibiting significant impairments on the working memory tasks, the animals received intermittent coadministration of a selective D, agonist, ABT 431. All monkeys showed deficits on the spatial and/or object working memory tasks during chronic haloperidol treatment relative to their pre-haloperidol baseline. Intermittent coadministration of a D, agonist improved the animals’ performance to pre-haloperidol levels. The ameliorative effects of D, agonist administration on cognition were progressive and long-lasting. D, agonist reversal of cognitive deficits in chronically haloperidol-treated monkeys has potential significance for clinical trials in neuroleptic-treated schizophrenic patients whose cognitive deficits and negative symptoms often prove to be treatment resistant. (Research supported by Funds from Hoechst Marion Roussell.)

162

DEFICIENT GLOBAL MOTION PROCESSING IN SCHIZOPHRENIA

tasks when the linkage between the stimulus and response must be refreshed by working memory because different modalities or relatively unlearned responses are involved.

Y. Chen, K. Nakayama, D. Levy, S. Matthysse, P.S. Holzman Psychology Research Lab, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA Motion processing requires local and global extraction of both spatial and temporal information. We studied schizophrenic patients’ detection of coherent motion, which is not only explicitly based on signals integrated across the visual field, but is also directly linked to the functional activity of the middle temporal area (MT) in the brain. The task is to form a global motion percept (leftward or rightward) from a random-dot cinematogram. The stimuli contain a correlated motion signal, whose strength corresponds to the percentage of the dots moving in the same direction, as well as motion noise. The coherent motion threshold is defined as the minimal signal strength necessary to make 80% correct judgments, and was determined using a constant-stimuli method. Compared with those of normal controls (n = 8), the thresholds of schizophrenic patients (n = 12) were significantly elevated when the number of the dots was large (100 or 200) @
A COMPARISON OF MANUAL AND SACCADIC PERFORMANCE IN A PATTERN REPRODUCTION TASK

THOUGHT DISORDER AND SCHIZOPHRENIA: SPECIFICITY FAMILIAL AGGREGATION

AND

M. J. Coleman, D.L. Levy, V. Ramagopal, P.S. Holzman Psychology Research Laboratory, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478. USA

Thought disorder has long been regarded as a hallmark of schizophrenia (Kraepelin, 1986/1919; Bleuler, 1922/1951; Solovay, et al., 1987). The relatives of psychotic patients have also been shown to demonstrate increased thought disorder (Shenton et al., 1989). The authors continue this line of inquiry using the Thought Disorder Index (Johnston and Holzman, 1979; Coleman et al., 1993) to assess the quantity and quality of disordered thinking in schizophrenic and bipolar patients and their first-degree relatives. The results from this sample will be presented, and the implications of the findings will be discussed.

SPATIAL AND OBJECT WORKING MEMORY AND SCHIZOPHRENIA: SPECIFICITY AND FAMILIAL AGGREGATION

R. Cohen, B. Roberts and C. Schooler

M.J. Coleman, V. Ramagopal, C. Lavancher, J. Brownstein, G. Clark, D.L. Levy, S. Matthysse, P.S. Holzman

University Konstanz, Rektorat, D-78434 Konstanz, Germany

Psychology Research Laboratory, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA

Postfach

5560.

This presentation reports the results from a pattern reproduction task in which the stimuli are simultaneously presented visually and auditorily and in which the pattern is to be reproduced either through manual or voluntary saccadic movement. Both normal and schizophrenic subjects performed significantly worse when they had to respond with patterned eye movements. The schizophrenic subjects, however, were significantly more affected than the normal controls by having to make the relatively novel eye movement response. These results are congruent with other findings from this collaborative research program, which indicate that schizophrenic subjects have particular difficulties with experimental psychological

Schizophrenic patients have impaired spatial working memory (Park et al., 1992). The relatives of schizophrenic patients have also been shown to demonstrate deficits in spatial working memory (Park et al., 1995). The authors expound upon this line of inquiry using a spatial, delayed-response paradigm (Park et al., 1992) and a spatial versus object, working-memory paradigm (Smith et al., 1995). The sample includes schizophrenic and bipolar patients and their firstdegree relatives and normal control subjects. The results from this initial sample will be presented, and the implications of the findings will be discussed.

163

A PRELIMINARY STUDY OF THE EFFICACY OF A COMPREHENSIVE COGNITIVE REMEDIATION PROGRAM A STATE PSYCHIATRIC HOSPITAL A.D. Compton,

IN

M.J. Pilarc, D.E. Ross

Department of Psychiatry, Virginia Commonwealth Medical College of Virginia Campus Schizophrenia Unit, Central State Hospital, Box 4030, Petersburg, Virginia 23803, USA

University, Research

Since the early part of this century, deficits in cognitive processing (e.g., problems with sustained attention, working memory, verbal behavior, and/or executive function) have been noted in persons with schizophrenia and have been hypothesized to underlie associated abnormal behaviors. Recently, cognitive remediation modalities first developed for braininjured patients have been employed with schizophrenia patients in the hope of ameliorating cognitive deficits. Results of these studies have been equivocal but generally promising; however, the question of whether cognitive gains evidenced by test scores will generalize to non-therapeutic settings and persist remains open. Here, we report the results of a preliminary study of the first cohort (n = 6) of patients to enter a newly established, comprehensive Cognitive Remediation Program (Cog-Rem); pre- and 6-month-post-test scores on a limited battery of measurements were examined. Because of the small sample size, inferential statistics were not appropriate. Examination of individual subject data on Letter Scanning and Stroop Tasks suggested that, although the overall speed of information processing was increased, accuracy remained unchanged. On the Digit Span-Forward Task, four of the six patients improved. No trends were evident for Digit SpanBackward, Wisconsin Card Sort Test, or the Bender Visual Retention Test. Finally, we present a more comprehensive battery of tests, including measures of cognition, symptoms, social function, self-efficacy, quality of life, and community follow-up, which we plan for future studies in order to more fully address the questions of efficacy and persistence of gains with Cog-Rem. (Partially supported by a grant from the A.D. Williams Trust Fund, Virginia Commonwealth University.)

IMPAIRED CONDITIONAL DISCRIMINATION LEARNING SCHIZOPHRENIA K. Dantendorfer, Department Wiihringer

IN

E. Hofer, D. Maierhofer

of Psychiatry, University of Vienna, G&tell&20. A-1090, Austria

Introduction: Recent reports suggest that memory and learning deficits seem to be more specific to schizophrenia (SZ) than

previously accepted. Conditional discrimination learning (CDL) based on eyelid conditioning is selectively sensitive in testing temporal lobe function ‘(Daum et al., Behav Neurosci, 1991) and is not dependent on attentional capacities and motivation. Methods: An eyelid CDL task was used to examine 24 SZ patients (DSM-IV criteria; 12 paranoid type and 12 disorganized type) and 20 age matched healthy controls. All patients had been in clinically stable condition for at least 3 months and were under stable neuroleptic medication. The acquisition of conditioned responses and the difference in response frequency to reinforced (CRR) and unreinforced trials (CRU) were quantified. Results: All patients and controls acquired conditioned responses. There was no significant difference between the results of the 2 SZ-type groups. As expected, the controls showed a significantly higher rate of CRRs than CRUs (32% f 5.5% vs 14% _+ 3%). While SZ patients showed no difference in the CRU rates compared to the controls, they failed to acquire higher CRR rates. Conclusion: Our data show, for the first time, an impairment in temporal lobe-related learning abilities in a motivationindependent task in clinically stable SZ patients. Thus, impaired CDL ability might be a trait marker in SZ.

MODELING SCHIZOPHRENIC BEHAVIOR AND TESTING DRUG EFFICACY USING GENERAL MIXTURE COMPONENTS ON FINGER TAPPING DATA FROM A TWELVEMONTH PROSPECTIVE DOUBLE-BLIND CLINICAL TRIAL S.R. David, D.B. Rubin, Y. Wu Eli Lilly and Company, Indiana 46285, USA

Lilly

Corporate

Center,

Indianapolis,

Schizophrenia, a word introduced by Bleuler (1911), is a term used to describe a person with a mixture of deranged and intact thought processes. Current theory suggests that the thought processes of people with schizophrenia are not only slower than those of nonschizophrenics, but also some people inflicted with this disease are further susceptible to additional disruptions in cognition or dialipses. Thus, schizophrenic behavior can be viewed as mixture of two states. The first one is a ‘non-dialipsis’ state, where the cognitive behavior of a subject is similar to that of a normal person but slower (e.g., due to motor skills). The other is a ‘dialipsis’ state, during which the patient shows abnormal cognitive behavior characterized by a significant delay in average performance accompanied by greater variability. The goal of scientific statistical modeling is to isolate the dialipsis component and assessthe effectiveness of drugs in limiting it. The challenge to the statistical analysis results from the fact that one can directly observe neither

164

whether a subject is susceptible to dialipses nor whether a subject is suffering from a dialipsis when a measurement is taken. This work proposes a novel and general mixture component model, the features of which include a hierarchical structure with random effects, mixture components characterized by ANOVA-like linear regressions, and mixing mechanisms governed by logistic regressions. The model will be applied to data from a prospective 12-month, multicenter, double-blind trial designed to compare the effects of olanzapine (5 to 20 mg), risperidone (4 to 10 mg) and haloperidol (5 to 20 mg) on a comprehensive battery of neurocognitive tests in patients with early phase schizophrenia or schiziphreniform disorder. For purposes of this paper, discussion of the results will focus on fine motor speed as measured by the Finger Tapping Test (FTT). Ten FTT trials (intervals of 10 seconds) were conducted at each of 4 cognition visits (baseline and after 6, 30, and 54 weeks on therapy).

COGNITIVE ATTRIBUTIONS IN PARENTS OF PATIENTS WITH EARLY-ONSET SCHIZOPHRENIA AND BIPOLAR ILLNESS: THEIR RELATIONSHIP TO PERSONAL AND FAMILY FUNCTIONING M.A. Davies, D. Cola, J. Vitkus, S.C. Schulz Department Cleveland,

of Psychiatry, Case Western Ohio 44106, USA

Reserve

University,

Studies in adults with schizophrenia and depression indicate that a caregiver’s cognitive attributional style (i.e., their belief concerning the cause of the mental illness) may be an important determinant of the caregiver’s psychological status and the family’s functional status. In this study, we investigated the relationship between parental cognitive attributes and two dependent measures (caregiver depression/anxiety and family functioning). Our sample consisted of 46 parents caring for persons with an early-onset serious psychiatric disorder (26 schizophrenia and 20 bipolar). Using well-established instruments, we measured the variables of interest through selfreports that were clinically useful and easy to administer. Our findings indicated that 40% of parents reported levels of depression/anxiety that could be clinically significant and that 40% of the families were rated as dysfunctional. In addition, parents who tended to blame a person (including themselves) were significantly more depressed/anxious and reported more family dysfunction than parents who tended to attribute the cause of mental illness to heredity/biological factors or to global causes (i.e., chance of God’s plan). As there were no significant differences between parents for the two diagnostic groups, these findings lend support to the utility of an attributional model in attempting to understand and manage caregivers and families of young persons with serious mental illness.

COGNITIVE DEFICITS IN RATS TREATED PRENATALLY WITH THE MITOSIS INHIBITOR METHYLAXYMETHANOL (MAM) AT DIFFERENT TIME POINTS DURING GESTATION M. Didriksen, F. Sams-Dodd, J. Arnt Psychopharmacology Department, DK-2500 Valby. Denmark

H. Lundbeck

A/S,

In recent years it has become more evident that schizophrenia, besides psychotic symptoms, also is associated with various cognitive deficits. Development of antipsychotic compounds with beneficial effect on the cognitive deficits is limited by the lack of relevant behavioral models. Evidence in recent years indicates that schizophrenia is a neurodevelopmental disorder, and one method of mimicking the disease is to interfere with normal developmental processes by pre- or neonatal manipulations using the mitosis inhibitor (Moore and Grace, Sot Neurosci Abstr, 1997; 23:2378; Grace et al., Int J Psychopharmacol, l(1 ):S24). In the present study we have administered MAM (20 mg/kg, ip) on gestation day E9, ElO, El], E12, El3, E15, or El7 to different groups of pregnant rats. The offspring of the treated pregnant rats were tested at 3.5 months of age in the Morris water maze, a model for spatial learning and memory. Rats treated on day El7 were impaired compared to controls. Rats treated on all other days were unimpaired. Furthermore, the rats treated on day E13, E15, or El7 were subsequently tested in an object recognition task, a model for episodic memory at 4 months’ age. In this task, rats treated on day El5 or El7 were impaired. Rats treated on day El3 performed at control level. The results in this model may be confounded by a reduction in investigation time in rats treated on day El5 or E17. Further studies have to clarify this. It is concluded that mitosis inhibition at day El5 or El7 during gestation induces cognitive disturbances in rats, probably by interfering with normal development. This may be a valuable model for testing treatment strategies for cognitive deficits in schizophrenia.

THE EFFECT OF ANTIPSYCHOTIC COMPOUNDS AND PSYCHOSTIMULANTS ON PERSERVERATION ERRORS IN RATS M. Didriksen Psychopharmacology Department. DK-2500 Valby, Denmark

H. Lundbeck

A/S,

It is well known that schizophrenia is associated with hypofunction of prefrontal cortex. One of the characteristic deficits of patients with hypofrontality is a tendency to perseverate on the Wisconsin Card Sort Test. In this task, patients are required to sort a pack of cards containing symbols that vary in three dimensions (color, shape, and number) according to a rule

165

based on one of those three dimensions. Hypofrontality patients frequently continue to sort cards according to the previous rule (perseveration), even when the rule has been explicitly changed. In the present study, we have investigated the effect of different antipsychotic compounds and psychostimulants on perseveration in rats. Rats are trained to respond on one of two levers for reward. After five correct responses in row, the reinforced lever is changed. Continued responding on the previously reinforced lever is considered as perseverative errors. Scopolamine and the classical antipsychotic compound haloperidol result in an increase in perseverative errors, whereas clozapine and sertindole are without effect. Olanzapine, amphetamine, phencyclidine, the cc,-adrenoceptor antagonist prazosin, the histamine Hi antagonist mepyramine, the serotonin SHt,, antagonist MDL 100.151, and the benzodiazepine diazepam have not been tested yet. However, obtained data with these compounds will be included at presentation. The results indicate that dopamine D, and muscarinic receptor antagonism lead to increased number of perseverative errors in the present test condition. As schizophrenic patients already show decreased performance in such tasks, further impairment is an unwanted effect. A goal for novel antipsychotics is to improve cognitive function. However, the rats in this study have near optimum performance, and accordingly, improved performance cannot be expected.

AFFECTIVE REACTIVITY OF SPEECH IN SCHIZOPHRENIA PATIENTS AND THEIR NONSCHIZOPHRENIC RELATIVES N.M. Docherty, Department Ohio 44242,

C. Geis, M.J. Hall, SW.

of Psychology,

Kent State

University,

Gordinier Kent,

USA

Nonschizophrenic relatives of schizophrenia patients as a group have demonstrated certain subtle language and communication disturbances. Thought, language, and communication symptoms in schizophrenia patients are exacerbated by arousal of negative affect in the patients. The present study compared frequencies of referential communication disturbances in speech samples from 41 stable schizophrenia outpatients, 46 parents of patients, and 23 nonpsychiatric control participants in affectively positive versus affectively negative conditions. The speech of the patients and parents showed elevated frequencies of reference failures in the affectively positive condition compared with control participants; the speech of the patients became more disordered in the affectively negative condition, whereas the speech of the parents did not. These results support the idea that referential communication disturbances may reflect vulnerability as well as overt illness, but that affective reactivity of these disturbances is associated mainly with the manifest illness. These findings are consistent with biological, cognitive, and psychological theories about the processes underlying stress-responsiveness of schizophrenic symptoms more generally.

SHORT-TERM MEMORY FOR SERIAL ORDER IN SCHIZOPHRENIA: A DETAILED EXAMINATION OF ERROR TYPES B. Elvevbg, T.E. Goldberg Clinical Brain Disorders Branch, National Institute of Mental Health. National Institutes oJHealth. Building 10, Room 4C215, Bethesda, Maryland 20892, USA Cognitive deficits in schizophrenia have been associated frequently with problems in working memory, yet the tasks used are often multifaceted, making it difficult to ascribe performance reductions to specific psychological processing components. We assessed the ability to maintain order information by employing simple short-term serial memory tests, which require the recall of a list of letters from the first item to the last item in the order in which they were presented. Different types of impairments will lead to different error patterns. A deficient representation will lead to an increase in ‘movement’ errors (e.g., A-B-C-D being recalled as A-B-D-C), rather than ‘intrusion’ errors (e.g., A-B-C-D being recalled as A-B-C-X). Impaired inhibitory function will lead to an increase in ‘perseverative’ errors (e.g., A-B-C-D being recalled as A-B-C-B), whereas decay of the memory trace will lead to ‘omission’ errors (e.g., A-B-C-D being recalled as A-B-C-). Such detailed error analyses are not generally reported in the neuropsychological literature; thus, we present this data from 24 schizophrenic patients and 29 control subjects. The disproportionate errors made by patients were omissions (and not movements, intrusions or perseverations), and occurred mainly at the end of the list. We conclude that schizophrenic patients’ limited short-term memory span may be explicable in terms of greater forgetting during output due to slower responding or other limitations, and is not attributable to a selective deficit in memory for serial order.

IS AUDITORY IMAGERY ABNORMAL SCHIZOPHRENIA PATIENTS WITH AUDITORY HALLUCINATIONS? C. Evans, P.K. McGuire,

IN

A.S. David

Department of Psychological Medicine, Medicine and the Institute of Psychiatry,

King’s College School of London, SE5 8AF, UK

Most psychological theories of auditory verbal hallucinations (AVH) postulate that they are a form of inner speech which becomes mis-labelled as non-self. This may result from abnormal auditory imagery or monitoring systems. We carried out an in-depth study of 7 patients with no history of AVH and 12 with a strong history of AVH, using auditory imagery paradigms which tapped into the functioning of the ‘inner ear,’ the ‘inner voice,’ and the ‘inner ear - inner voice’ partnership. These included: parsing meaningful letter strings, pitch judgements, verbal transformations, and a range of tasks requiring phonological judgements. The results showed a wide range of

166

abilities and deficits in both groups but no clear pattern. Indeed, the AVH group were somewhat superior. Analysis of individual cases showed that performance on none of the tasks was consistently impaired and, on some, patients achieved maximum scores. These results provide evidence against an abnormality in inner speech and phonological processing in patients vulnerable to AVHs and point towards metalinguistic models, or those based on lower-level perceptual processes.

PROCESSING SPEED ACROSS MULTIPLE COGNITIVE DOMAINS IN SCHIZOPHRENIA

involving speeded attention and learning (Digit-Symbol Substitution Test: p < 0.005). There were also trends toward improvement on Trials B (p ~0.05) and Verbal Fluency (p < 0.06). In addition, there was a trend for Delayed Word Recall to be adversely affected by quetiapine @ = 0.09). Our results were based on a small sample, following a short trial, and therefore must be viewed with caution and as preliminary. Moreover, although alternate forms were utilized, subjects received placebo first, thereby highlighting the possibility of order effects. Despite these caveats, the findings do warrant future trials comparing the neurocognitive effects of quetiapine with those of standard and atypical agents.

A. Fischer, A. Murray, J. Poole, S. Vinogradov University

of California,

San Fransisco.

California

94121,

USA

Prior studies of information processing in schizophrenia have suggested the presence of slowed processing in many cognitive domains and that this effect worsens the task complexity. However, the extent to which this slowing is generalized across all tasks or is specific to certain cognitive domains (e.g., attentional, executive, verbal) has not been established. We compared 89 medicated, clinically stable schizophrenic outpatients and 27 control subjects, matched for age and gender. We administered ten nemopsychological tests assessing speed and accuracy across multiple cognitive domains (attention, executive functions, receptive and expressive language, motor efficiency, and affect perception), yielding 22 measures of response time, with means ranging from 0.2 to 7.0 seconds. Regression analysis was used to compare mean response times (controlled for age) in the two samples. This analysis found a generalized linear slowing in the schizophrenic sample (average 26% slower performance across tasks), which accounted for 98.6% of the variance in mean response times across all tasks. We did not find evidence of domain-specific slowing in the schizophrenic group, above and beyond this generalized linear model. This study highlights the pervasive effects of generalized slowing across multiple cognitive domains in schizophrenia.

THE NEUROCOGNITIVE EFFECTS OF QUETIAPINE: A PRELIMINARY INVESTIGATION K. Fleming, P. Thyrum, C. Yeh, D. Vargo, S.G. Potkin Department California

of Psychiatry, 92868, USA

University

of California,

Irvine,

The goal of this preliminary study was to determine the potential neurocognitive effects of quetiapine fumarate (quetiapine, ‘Seroquel’), a new ‘atypical’ antipsychotic. Eighteen men with psychotic disorders from two small trials were given neurocognitive tests after single-masked placebo (5 to 8 days) and quetiapine (250 mg tid, 10 days) treatments. Compared to placebo, quetiapine significantly improved a complex measure

THE CLINICAL BASIS OF COGNITIVE IMPAIRMENT IN ELDERLY PATIENTS WITH SCHIZOPHRENIA VS. Gabrovska, A.E.P. Mitchell, J.F.W. Deakin, SW. Lewis, A. Burns The University of Manchester, School of Psychiatry and Behavioural Sciences, Department of Old Age Psychiatry, Withington Hospital, Cavendish Ward, West Didrbury, Manchester M20 8LR, UK

It is not clear whether there is a progressive element to the cognitive impairment of schizophrenia. We have hypothesised that frontal lobe impairment may be the static genetic endophenotype and that there is a progressive temporal lobe component (J.F.W. Deakin et al., J Psychopharmacol, 1997;l l(2): 133-142). We have tested this hypothesis by characterising the cognitive impairment in demented (Mini-Mental State Examination < 23) and nondemented (MMSE < 24) elderly patients with schizophrenia (> 60 yrs; n = 37; illness onset < 45 yrs). As we have previously reported, nondemented patients perform less well in recognising faces than they do in recognising words from previously presented lists in the Warrington Recognition Memory Test. In contrast, in patients with dementia, word recognition was as impaired as face recognition (subtest by diagnosis interaction; p = 0.02). In keeping with progressive temporal-lobe dysfunction, demented patients were impaired in design learning. However, they were not impaired in word-list or story-recall. Patients with schizophrenia and dementia were impaired on Stroop colour-word conflict compared to nondemented patients. The groups did not differ in positive or negative symptom severity. These preliminary results suggest that severe cognitive impairment in elderly patients with schizophrenia may be associated with progressive temporal-lobe impairment (word recognition), as predicted. However, there is additional impairment of frontal-executive function over and above that seen in nondemented patients.

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ATTENTIONAL DELUSIONS M. Gorissen,

BIAS IN PERSECUTORY

S. de Koning

Veldwrjk Research The Netherlands

Institute,

PO Box 1000, 3850 BA Ermelo,

One explanation for the maintenance of delusional beliefs is the preferential encoding of information that is in line with the delusion. Previous studies with the Stroop test, in which subjects are required to name the ink colors of words, have shown an attentional bias for words of threatening nature in patients suffering from persecutory delusions. Moreover, studies suggest a pattern of information processing biases similar to those in depressed patients. However, these studies were not controlled for the general negative emotional salience of the words. We therefore tried to examine the attentional bias for neutral and happy words, and for words with different negative emotional value (anxiety, depressive, thread-related), in depressive patients, paranoid schizophrenia patients, nonparanoid schizophrenia patients and matched healthy controls. Attentional bias was measured in a Stroop paradigm, in which the interference in color-naming the emotion words was taken as an index for emotional attention bias. A specific bias for depressive words only was expected in the depressed patients. A bias for threat-related and depressive words, but not for anxiety words, was hypothesized in the paranoid patients, Results did not confirm our hypotheses; paranoid patients were slower in all conditions, but no specific attention bias was found. Results show the importance of controlling for emotional salience in ‘emotion Stroop tasks.’

DEVELOPMENT OF A CONTEXTDEPENDENT LATENT INHIBITION N.S. Gray, M. Fernandez, The Caswell Wales, UK

Clinic,

Glanrhyd

a virtual environment. As predicted, a significant Ll effect was found in healthy volunteers when preexposure and test occurred in the same context, but was disrupted when context was altered. The results constitute the first demonstration of a context-dependent Ll effect in human subjects.

TASK

M.A. Good, R. Ruddle Hospital,

Bridgend

CF314LN,

Latent Inhibition (LI) relates to the retardation of conditioning following repeated nonreinforced preexposure to the conditional stimulus. LI is abolished in schizophrenia (N.S. Gray et al., Schizophrenia Research, 1995;17:95-107). Animal studies have shown that LI is context-dependent. Therefore, it was hypothesised that the abolition of LI in schizophrenia may reflect inappropriate processing of context. In order to investigate this hypothesis we need to demonstrate a context-dependent effect of LI in a human population. The development of such a task would enable the measurement of use of context in associative learning in schiozphrenia and how this relates to symptom type and severity. The LI task involved preexposure of a triangular border (the to-be-conditioned stimulus) around nonsense trigrams. In the test phase subjects were required to learn that the triangle border signalled increments in a visual counter score (the unconditioned stimulus). Context between preexposure and test was either kept constant or changed using

JUST HOW BAD ARE ADJUNCTIVE ANTICHOLINERGIC MEDICATIONS? M.F. Green, B.D. Marshall, M. McGee, J. Hayden UCLA Neuropsychiatric Los Angeles, California

R.S. Kern, K.S. Kee,

Institute, C9-420, 90024-I 759, USA

760 Westwood

Plaza,

Anticholinergic medications are frequently given to schizophrenic patients to help control extrapyramidal symptoms (EPS) associated with antipsychotic medications. Anticholinergic medications are considered detrimental to neurocognitive processes, but the range of this impairment is unknown. Sixteen treatment-resistant schizophrenic patients who were receiving both antipsychotic medications and benztropine had their doses of benztropine adjusted while antipsychotic medication was held constant. Benztropine was administered at 6 mg per day for 2 weeks before being titrated downward over 3 days and discontinued. Patients were monitored daily and were reinstated on 6 mg of benztropine for any worsening in EPS. A neurocognitive battery that selectively assessed secondary memory (Wechsler and Rivermead tests) and early perceptual processes (dichotic listening and backward masking tests) was conducted when patients were receiving 6 mg and after discontinuation. Twelve of the 16 patients (75%) showed increased EPS within 3 weeks of discontinuation, including clinical need for benztropine. As expected, secondary memory improved significantly @ < 0.05) as benztropine went from 6 to 0 mg. In contrast, early auditory and visual processing were essentially unchanged. The results suggest that chronic use of anticholinergic medications may have neurocognitive costs that are selective for memory, as opposed to perceptual, processes.

THE NATURE OF SEMANTIC REPRESENTATIONS: WHAT CAN WE LEARN FROM PATIENTS WITH SCHIZOPHRENIA? N.E.A. Green, D.J. Done, S.H. Anthony, D.G. Nevison-Andrews Department of Psychology, University College Lane, Hatfield, Herts. ALIO

C. Hawley,

of Hertfordshire, 9AB, UK

Within the last decade, a considerable body of literature has accumulated which suggests semantic-memory deficits are prevalent in patients with schizophrenia. However, such research has been grounded in traditional theories of semantic memory,

168

which assume that conceptual knowledge is decontextualized (i.e., uninfluenced by task constraints). This view has since been widely criticised. Recent research suggests that semantic representations are not static, but the product of a dynamic system This study utilises the method employed by Payne and colleagues, and looks at patients who over/underinclude (i.e., have overly flexible or restrictive conceptual boundaries). A series of tasks was designed in order to investigate the stability of these conceptual boundaries. Data were collected from a sample of 25 patients with a DSM IV-diagnosis of schizophrenia. Some 40% of these patients were identified as over/underincluders. In this subset of patients, semantic boundaries were found to be disorganised in some contexts, but perfectly intact in others. However, in other patients there seems to be a fairly consistent tendency towards over/ underinclusion across tasks. Therefore, preliminary findings suggest disturbed concepts in schizophrenia occur within a dynamic system, and this explains why the impairments are task- and context-dependant.

‘THEORY OF MIND’ IMPAIRMENT IN SCHIZOPHRENIA: COGNITIVE AND SYMPTOM CORRELATES

SEX DIFFERENCES IN TEMPORAL-LIMBIC FUNCTION IN SCHIZOPHRENIA: RELATION OF MEMORY TO STRUCTURAL AND FUNCTIONAL MEASURES R.E.

Gur,

Department Philadelphia,

J.D.

Ragland,

of Psychiatry, Pennsylvania

B.I. Turetsky, R.C. Gur University of Pennsylvania. 19104, USA

Sex differences have been observed in cognitive, neuroanatomic, and functional imaging studies of healthy people. Healthy women tend to have better verbal memory, higher percent of gray matter tissue, and higher rates of regional cerebral blood flow (rCBF). In schizophrenia, sex differences have been noted in important clinical variables that may relate to brain-behavior relations. This study compared sex differences in memory function for healthy and patient samples and related them to sex differences in neuroanatomic and functional imaging measures. Sex differences were observed across groups for neurocognitive, MRI and PET measures of CBF, but some sex by diagnosis interactions were also significant. The results suggest that gender may moderate the effects of disease factors in schizophrenia.

T.C. Greig, M.D. Bell, G.J. Bryson VA Connecticut Healthcare System and Yale University of Medicine, Department of Psychiatry, West Haven, Connecticut 06516, USA

School

Impaired ‘theory of mind’ skills have been noted in pervasive developmental disorders and have been proposed as an underlying feature of social impairment in schizophrenia. Previous research employing Corcoran’s ‘Hinting Task’, which requires the subject to infer the meaning of indirect statements, found that people with schizophrenia performed worse than normal controls and that subjects with residual schizophrenia performed better than those with prominent negative symptoms, passivity symptoms, and paranoid delusions. The present study examined the relationship between Corcoran’s ‘Hinting Task’ performance and symptoms, suband representative neuropsychological measures. types, Subjects were 24 outpatients with diagnosis of schizophrenia participating in a work rehabilitation program. Results indicated that hinting task performance was highly correlated with thought disorder @
HASSLES AND UPLIFTS SCHIZOPHRENIA

IN

N. Haigh Department Humberside,

of Psychology, University Hull HU6 7RT, UK

of Lincolnshire

and

Current approaches to the management of schizophrenia emphasize the influence of psychosocial stress on the course of illness. Past research proposed that individuals with schizophrenia may experience more stress from the adaptational demands of minor life events (hassles) than major life events. The stress and coping literature suggests that uplifts (positive events) may moderate stress by reducing the potential or actual impact of the stressful experience. This study aims to explore the hassles and uplifts experienced by individuals with schizophrenia and to examine their relationship to perceived stress and coping ability, depression, and general psychiatric morbidity. Patients diagnosed with schizophrenia and a ‘normal’ group will be asked to recall and describe a recently experienced hassle and uplift, respond to a series of open-ended questions, and rate each event along a set of cognitive appraisal dimensions. The Hassles and Uplifts Scales, PSS, BDI, GHQ-28, and PERI will be employed to examine relationships between hassles and uplifts, perceived stress and coping ability, depression, and general psychiatric morbidity. It will be hypothesised that the data will demonstrate the significance of uplifts in schizophrenia.

169

REALITY DISTORTIONS IN SCHIZOPHRENIA: RELATIONSHIP BETWEEN THOUGHT DISORDER DELUSIONAL ACTIVITY

AND

M. Harrow, E.S. Herbener, E.M. Martin, J.T. Marengo, J.M. Racenstein, T.H. Jobe Department Medicine.

of Psychiatry, University of Illinois, College of 912 South Wood Street, Chicago, Illinois 60612, USA

Goal: New three-factor theories about the symptom complex in schizophrenia suggest separate mechanisms underlying different types of reality distortions, such as though disorder and delusions. The present research analyzed the relationship between thought disorder and delusions on a longitudinal basis, over a 15-year period, to determine whether vulnerability to formal thought disorder might be linked to vulnerability to other types of reality distortions, such as delusions and hallucinations. Method: One hundred and eighty seven patients from the Chicago Follow-up Study, including 56 schizophrenia patients, were assessed at the acute phase and then followed up 5 times over the next 15 years. At each assessment the patient sample was evaluated with three standardized measures of formal thought disorder. They were also administered structured interviews to assessdelusions and hallucinations. Results: (1) The data indicate a significant relationship between thought disorder and delusions at each of 5 followups over 15 years (p i 0.05); (2) Schizophrenia patients who were thought-disorder at each follow-up were significantly more likely to be delusional at the next follow-up, 3-5 years later (p < 0.05); and (3) The relationship between thought disorder and hallucinations was not a strong one. Conclusions: The data do not support simple three factor theories of schizophrenia symptoms. The significant relationship between thought disorder and delusions suggest that a vulnerability to some common factors plays a role in different types of reality distortions. Other data of ours suggest a deficit in self-monitoring as one of several underlying factors common to different types of reality distortions in schizophrenia.

EYE GAZE DIRECTION PERCEPTION SCHIZOPHRENIA PATIENTS C. Hooker,

IN

S. Park

Department of Psychology. Illinois 60208, USA

Northwestern

University,

we still do not know the exact nature of the deficit nor its consequences. We propose that part of schizophrenia patients’ face processing deficit is an inability to accurately judge eye gaze direction. Eye gaze direction communicates important information about social situation and theory of mind. Therefore, an inability to judge the eye gaze direction may lead to a misinterpretation of important social cues. We tested 17 schizophrenia patients and 17 normal control subjects on an eye gaze direction perception task. Schizophrenia patients show a deficit in judgment of eye gaze direction as compared to normals. It is not clear from the study whether this deficit is due to a deficit in early visual information processing or a deficit specific to processing faces. Further research should elaborate the specificity of the deficit and its possible consequences in social functioning.

RELATIONSHIP BETWEEN DURATION OF ILLNESS AND COGNITIVE DECLINE IN CHRONIC SCHIZOPHRENIA R. Hoshino, N. Takei, M. Yokoi, Y. Ishizuka, R. Sato, N. Mori

M. Mizukoshi,

Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan

Hamamatsu,

We examined a verbal IQ (VIQ) from WAIS-R, as a parameter of cognitive function in 63 (M/F:31/32) chronic patients with DSM-IV schizophrenia: mean age (SD) 62.1 years (6.8), with the range 50-74; mean duration of illness 35.1 years (9.2) ranging from 12 to 52 years. They were all inpatients who had been hospitalized in psychiatric hospitals for many years; mean duration of the last hospitalization was 25.2 years (8.7), with the range of 6 to 41 years. The average VIQ was 74.8 (10.9), with the range 51-102. Multiple-regression analysis, in which years of education, sex, and age-at-onset were adjusted, revealed that the VIQ associated with duration of illness varied with sex. Separate analysis for sex showed a more cognitive deficit over the course of illness in female than in male schizophrenics; a 3-point fall (95% confidential interval -9.4 to 3.7) every 10 years after onset for the former, a l-point fall (95% confidential interval - 7.6 to 5.4) for the latter. Neither age-at-onset nor period of hospitalization was a good predictor for the cognitive decline. (N.T. is a Stanley Foundation research fellow.)

Evanston,

Many studies indicate that schizophrenia patients do not accurately ascertain information from facial cues. Schizophrenia patients have reliable deficits in facial emotion perception and face recognition tasks. Several studies have also shown that schizophrenia patients have abnormal visual scan paths when judging facial stimuli. Despite the evidence suggesting deficits in gaining accurate information from facial stimuli,

COGNITIVE DEFICITS AS CORRELATED PHENOTYPES FOR GENERIC RESEARCH IN SCHIZOPHRENIA A. Jablensky, A. Kent, H. Wichmann, Department of Psychiatry, Perth WA 6000, Australia

University

J. Box

of Western

Australia,

170

There is growing evidence that: (1) schizophrenia is genetically complex and heterogeneous; (2) multiple genes interacting with environmental factors contribute to its causation; (3) schizophrenia is not inherited as a unitary disorder; and (4) ICD-IO or DSM-IVdiagnoses do not provide the phenotype resolution that is required for genetic analysis. As an alternative to the disease category, the clinical syndrome of schizophrenia can be conceived as a ‘fuzzy set’ resulting from interactions between a number of independent phenotypes, each having a separate pathophysiological and genetic basis. Such phenotypes may be expressed as neurocognitive or neurophysiological abnormalities, or as measurable traits and behaviours, common in schizophrenic subjects and in a proportion of their unaffected biological relatives, but rare in the general population. Results from a study of 100 schizophrenic probands and 234 flrstdegree relatives, with detailed assessment of psychopathology, neurological signs, neurocognitive functioning, and personality traits, indicate that IQ decrements, deficits of sustained attention (CPT-DS d’) and of working memory; high scores on the novelty seeking trait; and anhedonia tend to cluster in families irrespective of the ZCD-lO/DSM-IV affection status of their members. These measures may represent facets of a common vulnerability marker suitable for QTL analysis.

COPING WITH STRESS IN SCHIZOPHRENIA L.M.C. Jansen, C.C. Gispen-deWied,

R.S. Kahn

Department of Psychiatry, University Hospital Utrecht. PO Box 85500. 3584 CX Utrecht. The Netherlands

In the vulnerability-stress model for schizophrenia, schizophrenic patients are thought to have an increased vulnerability to stress. In this study, the coping styles in relation to stress of 19 schizophrenic patients were compared with 22 healthy controls. The Utrecht Coping List (UCL) was filled out to measure general coping styles. The Ways of Coping Checklist (WOC) was used to measure situation-specific coping in a psychosocial-stress test situation (public speaking). The publicspeaking test was imbedded in a two-hour test session and compared to a control session without stress induction. cortisol was measured every lo-20 minutes. Schizophrenic patients generally use more passive (MannWhitney U-tests: U = 63.5, p < 0.001) and avoidant coping styles (U = 88.0, p < O.Ol), and less-active coping styles (U = 112.5, p < 0.05) than controls. Patients used more escape/advoidance (U = 56.5, p < 0.01) and less-planful problem solving than controls (U = 63.0, p ~0.01) during the psychosocial stress test. Cortisol responses to the test were blunted in patients (t-test: t = -2.93, p
IMPAIRED INHIBITION OF AUTOMATED COGNITIVE PROCESSES IN SCHIZOPHRENIC PATIENTS J.M. Jansma, N.F. Ramsey, RX

Kahn

Department of Psychiatry, University Hospital Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

Some of the cognitive deficits implicated in schizophrenia may be explained in terms of a reduced ability to shift between controlled and automatic processing. In this study we test this hypothesis through a reaction-time, Sternberg task-protocol, designed for use in an event-related fMR1 experiment. Eleven healthy controls and nine schizophrenic patients performed two Sternberg tasks (to recognize one from six targets among six non-targets as rapidly as possible, ISI:2s, 120 trials per task). Both tasks were similar, except that targets and nontargets were reversed in the second task (target becomes nontarget and v.v.). Reaction times on targets on the first and the last 25 trials of each task were analyzed. Both patients and controls showed a significant effect of practice on reaction times (task 1: F,,,, = 14.78; p < 0.01, task 2: F,,,, = 12.09; p i 0.01). Whereas task performance in task one was the same, patients were significantly slower than controls in task two (F,s.l = 5.72; p ~0.05). Patients and controls showed no differences in number of errors on task one or task two. Results suggest that schizophrenic patients can shift from controlled to automatic processing as do healthy controls, but show a reduced ability to show from automatic to controlled processing, possibly due to an impaired ability to inhibit automated responses.

IMPAIRED VERBAL SELF-MONITORING AND AUDITORY VERBAL HALLUCINATIONS L.C. Johns, S. Rossell, F. Ahmad, C. Frith, D. Hemsley, E. Kuipers, P.K. McGuire Department of Psychology, London SE5 8AF, UK

Institute

of Psychiatry

Auditory verbal hallucinations in schizophrenia may result from impaired self-monitoring of inner speech. We examined whether patients with schizophrenia had a verbal self-monitoring deficit, and whether this was specific to auditory verbal hallucinations. Ten hallucinations (patients with delusions and daily auditory verbal hallucinations), 8 non-hallucinations (patients with delusions only), and 20 volunteers were tested. Subjects read out single words (complimentary, derogatory, or neutral adjectives) under the following conditions: reading aloud or reading aloud with acoustic distortion of the subject’s voice. Subjects judged whether the speech they heard was their own voice or not. When reading aloud and hearing their own voice distorted, patients in both groups made more errors (misattribution errors

171

and unsure responses) than controls @ = 0.04). Compared to non-hallucinators, hallucinators made more misattribution errors (p = 0.015), and more errors when identifying the source of derogatory adjectives (p = 0.03). The results indicate that defective verbal self-monitoring is evident in patients with schizophrenia and auditory verbal hallucinations, but also in hallucination-free patients with delusions. Hallucinators were distinguished by a tendency to misattribute their own voice and negative material to an external source.

IMPAIRMENT IN VERBAL LEARNING AND ENCODING PROCESSES DURING CONSECUTIVE RECALL TASKS IN PATIENTS WITH SCHIZOPHRENIA D.-I. Jon, K.-R. Chung, C.-H. Kim, H.-S. Lee Department Medicine,

of Psychiatry, Seoul, Korea

Yonsei University

College

of

Learning is very important in treatments such as cognitive training and pharmacotherapy as well as in quality of daily life in patients with schizophrenia. This study examined verbal learning performance in schizophrenia using a word list to investigate the pattern of learning impairment and its relationship to encoding processes. Subjects consisted of 26 patients with schizophrenia and 22 normal controls. Verbal learning was evaluated with computerized tasks composed of 3 consecutive immediate recall tests, a yes/no recognition test, and a delayed recall of a word list. The patients showed impaired immediate recall performance. Although both groups showed a significantly gradual improvement in recall performance (F = 148.0, p = O.OOOl), the rate of learning in patients was poorer than in controls during consecutive recall tasks (group x time interaction, F = 11.4, p = 0.0001). However, both verbal recognition performance and forgetting were comparable in both groups. Similar to recall performance, the amount of clustering was decreased in patients and showed less of an increase over time than in controls (group x time interaction, F = 3.72, p = 0.03). Word clustering correlated significantly with recall performance. These findings suggest that learned information might be maintained in spite of impaired verbal learning and lend further support to their importance of encoding processes in verbal learning in schizophrenia.

RESPONSE TO TRAINING: DO PATIENTS WITH SCHIZOPHRENIA DIFFER FROM HEALTHY CONTROLS IN THEIR RESPONSE TO AUDITORY DISCRIMINATION TRAINING? A. Kakoyannis, K. Frey, M. Weiler, D.R. Medoff, A.C. Lahti, H.H. Holcomb, C.A. Tamminga Maryland Psychiatric Research Center, University PO Box 21247, Baltimore, Maryland 21228, USA

of Maryland,

When working with healthy volunteers (NV), investigators often observe steep learning curves. After the initial exposure to a task, the NV may improve in speed and accuracy during a brief additional time period and then exhibit a performance ‘plateau,’ a state that is relatively resistant to improvement with further training. In contrast, persons with schizophrenia (SZ) may exhibit unpredictable and discontinuous learning behavior over the course of multiple learning sessions. There may be extremely large differences in the learning curves of the different schizophrenic patients. In this study we have trained NV (n = 12) and SZ (n = 18) to recognize 2 tones that are similar to one another in frequency. Using a forced-choice design we studied subjects making tone recognition decisions. Two to 3 thousand trials were presented over 3 to 5 days of training. After training completion, subjects participated in cerebral blood flow studies to map the functional brain activity patterns associated with the recognition decisions. Response to training was assessedby comparing the initial frequency disparity associated with good accuracy (greater than 75%), against the frequency disparity used at the end of training (70-85% accuracy). Not only did both groups improve in their ability to distinguish tones that were similar, but both groups also displayed significantly less variability between subjects after training. These observations emphasize the usefulness of training in conjunction with functional neuroimaging.

SPATIAL DELAYED-RESPONSE, TASKEVALUATED, WORKING-MEMORY DEFICIT IN SCHIZOPHRENIA Y. Kawasaki, T. Nagasawa, J. Murayama Department of Psychiatry, Fukui 910-0846, Japan

Fukui

Prefectural

Mental

Hospital,

Spatial delayed-response task requires working-memory processes, because the subject must retain the memory of the location of the stimulus during the period of the delay. Spatial working memory was evaluated using computer-based delayedresponse task. Schizophrenic patients (n = 18) diagnosed by DSM-IV performed significantly worse than healthy controls (n = 16) on the spatial delayed-response task (t = 2.627, p = 0.013). Subsequent study of another schizophrenic cohort (n = 24) diagnosed by DSM-IV investigated relationships between the delayed-response task performance and the Wisconsin Card Sorting Test, the Word Fluency Test (letter and semantic categories), the Wechsler Memory Scale, or the Line Orientation Test. Poor performance on the delayed, response task were significantly correlated with more nonperseverative errors on the Wisconsin Card Sorting Test (r = 0.544, p = 0.007) and with poor performance on the logical memory of the Wechsler Memory Scale (r = -0.597, p = 0.003). The non-perseverative errors on the Wisconsin Card Sorting Test did not correlate with the logical memory of the Wechsler Memory Scale. These results indicated the presence of a dysfunctional prefrontaltempololombic system and rendered support for the assumption of working-memory deficit in schizophrenia.

172

IMPAIRMENT OF CONSCIOUSLY CONTROLLED USE OF MEMORY SCHIZOPHRENIA

IN

M. Kazks, J.M. Danion, L. Berthet, I. Amado, D. Willard, Ph. Robert, M.-F. Poirier INSERM Unite 405, Chnique Psychiatrique, Hopitaux Universitaires de Strasbourg, BP 426, 67091 Strasbourg France

Cede-x,

Recent studies of memory in schizophrenia have shown that explicit, but not implicit, memory performance is impaired. They have led to the hypothesis that schizophrenia is associated with a failure of consciously controlled, but not of unconscious (automatic), intluence of memory on performance. The aim of this study was to test this hypothesis using a procedure providing uncontaminated estimates of consciously controlled and automatic-memory processes; i.e., the process-dissociation procedure in a stem-completion task. Performance of 35 patients with schizophrenia was compared with that of 35 normal subjects. Consciously controlled use, but not automatic influences, of memory was significantly lower in patients with schizophrenia than in control subjects. Consciously controlled use of memory was negatively and significantly correlated with positive symptoms of schizophrenia, such as auditory hallucinations and disorganization. These results indicate that schizophrenia affects differentially two types of memory processes, impairing consciously controlled use of memory while sparing automatic influences. They are compatible with the view that positive symptoms of schizophrenia occur because of the lack of control from higher-level conscious processes.

ASSOCIATIONS BETWEEN PERCEPTION OF EMOTION AND TYPES OF PSYCHOSOCIAL FUNCTIONING IN SCHIZOPHRENIA K.S. Kee, J.S. Brekke, D.F. Salveson, M.F. Green Department of Psychiatry and Biobehavioral Sciences, University of Cahyornia, Los Angeles, West Los Angeles Medical Center, 11301 Wilshire Boulevard (B116AR), Los Angeles, California 90073, USA

VA

The ability to perceive emotion in others appears to be critical for social competence. Although schizophrenic patients generally show deficits on measures of perceptions of emotion, little is known about the specific aspects of psychosocial outcome that are associated with these deficits. The present study was a prospective, longitudinal study of 29 schizophrenic patients following 12 months of a community-based rehabilitation program. Measures of emotion perception included tests of facial emotion, voice emotion, and affect perception. Psychosocial functioning was assessed using the Strauss and Carpenter Outcome Scale, and Role Functioning Scale. All measures were administered at baseline and 12 months. At

baseline, moderate cross-sectional associations were found between measures of perception of emotion and independent living (Y = 0.36, p = 0.06), and family network relationships (r = 0.34,~ = 0.08). At 12 months, patients’ emotion perception was positively correlated with work productivity, family network relationships, and useful employment, coefficients ranging from 0.36 to 0.44 @ = 0.02 to 0.06). The longitudinal relationships (between baseline emotion perception and later psychosocial functioning) were in the same direction but were weaker and not significant. These findings suggest that perception of emotion is associated cross-sectionally with both social and vocational outcomes.

SUCCESSFUL TREATMENT OF SELFMONITORING DEFICITS PREDICTS PSYCHOTIC SYMPTOM DECREASE R.S.E. Keefe, A.M. Bollini, M.C. Courtney, W.H. Wilson, J.P. McEvoy Department of Psyrhiatry Duke University Medical 27710, USA

and Behavioral Center, Durham,

Sciences. North Carolina

Patients with schizophrenia have cognitive deficits in monitoring the source of information they obtain, especially selfgenerated information. We examined the effect of antipsychotic treatment on these deficits in 20 patients with schizophrenia or schizophreniform disorder. Subjects were asked to recall the source of words that were read, identified from pictures, or self-generated. Patients were interviewed to determine the presence of specific hallucinations and delusions. Patients were assessed at baseline, and 2, 4, and 6 weeks after treatment. Treatment for 6 weeks decreased target symptoms (t =2.97, df= 13, p =O.Ol), and improved ability to recognize selfgenerated words (t = 1.76, df= 14, p = O.lO), and identify the source of self-generated words (t = 2.03, df = 15, p = 0.06). The number of target symptoms present at week 6 correlated significantly with deficits in identifying the source of selfgenerated words (r = 0.66, df = 12, p = 0.01) and the tendency to missidentify self-generated words as coming from the heard source (r = 0.70, df = 12, p = 0.006). The presence of voices commencing at week 6 correlated with these misidentification errors (r = 0.75, df = 12, p = 0.002) and with deficits in identifying the source of self-generated words (r = 0.72, df = 12, p = 004). Most importantly, improvement in the recognition of self-generated words from baseline to week 4 of treatment predicted total target symptoms at week 6 (r = 0.48, df= 13, p = 0.07). These results suggest a relation between self-monitoring deficits and specific symptoms of schizophrenia, and suggest that these deficits may be responsive to treatment.

SOURCE DISCRIMINATION IN PATIENTS WITH AUDITORY HALLUCINATIONS R. Kemp, S. Bhunoo, L van Huysteen University London,

Department UK

of Psychiatry,

Royal

Free Hospital,

173

Patients with schizophrenia have been found to make a range of errors in reality-monitoring tasks, and it has been suggested that difficulty in distinguishing the origin of stimuli may be linked with psychotic symptoms. For example, several studies have indicated that patients with auditory hallucinations (VH) show a tendency to attribute internally generated stimuli as being externally generated. However, it is unclear if these deficits reflect general cognitive impairment, and also how specific are such source discrimination errors. The effect of manipulating the emotional content of material is of considerable interest, given that the content of VH is typically emotive and unpleasant. Furthermore, the question of whether such deficits may be ‘state’- or ‘trait’-related has not been addressed. The aims of the current study were: (1) to investigate sourcediscrimination performance in hallucination-prone, psychotic patients who were currently symptomatic, and again when free of hallucinations, and to compare the results with that of a matched sample who were ‘trait-negative’ (no VH in 5 years); and (2) to further clarify the link with neurocognitive variables. Subjects with DSMIV schizophrenia or schizoaffective disorder completed a source-discrimination task in which they were required to identify items as self-generated, experimenter-generated, or new items. A second task required subjects to identify from which list was drawn a subset of words from two previously presented lists. A comprehensive assessment was performed composed of psychopathology ratings (SAPS and SANS, PANSS items, hallucination rating schedules), SAI-E insight schedule, NART-estimated IQ, Trails A and B, and EXIT and Paired Associates Learning Test. The results indicate characteristic deficits in source-discrimination performance and an association with neurocognitive impairment. The influence of emotional valence of items on error rate requires further exploration.

NEUROCOGNITIVE CORRELATES OF PROSOCIAL AND DEVIANT BEHAVIOR TREATMENT-RESISTANT SCHIZOPHRENIA INPATIENTS

IN

R.S. Kern, M.J. Robertson, N. Niv, L. Zaidel, M. Parsa, M.F. Green West Los Angeles VA Medical Center (B116AR), 11301 Wilshire Boulevard, Los Angeles, California

90073,

and early visual processing. On-unit behavior was assessed using the Time Sample Behavior Checklist (TSBC). The results revealed that vigilance and working memory were related to selected aspects of unit behavior. Other neurocognitive functions showed a weaker relationship to unit behavior. When these findings were reexamined partialling out the effects of positive and negative symptoms, the results remained essentially the same. These findings are largely consistent with previous studies which have shown a relationship between selected domains of neurocognitive functioning and functional outcome.

COMMUNICATION DEVIANCE ACROSS TASKS AND FAMILY MEMBERS IN THE FINNISH ADOPTION STUDY P. Keskitalo, K.E. Wahlberg, L.C. Wynne, J. Moring, I. Lahti, A. Sorri, M. Naarala, P. Tienari Department Finland

of Psychiatry,

University

of Oulu, FIN-90210

Oulu,

Communication Deviance (CD) measures problems in sharing foci of attention during communication. CD has been assessed from individual Rorschach protocols and from Spouse and Family Rorschach tasks, in which family members together explain and try to agree on their percepts. In the Finnish Adoptive Family Study of Schizophrenia, CD has been considered an environmental variable, disentangled from genetic risk in the adoptees’ study design. CD has been reliably measured from transcribed tapes obtained with 166 families, including 152 mothers, 121 fathers, and 146 adoptees tested individually, 121 marital couples tested with the Spouse Rorschach, and 146 families tested with the Family Rorschach. In rank ordering of subjects across tasks, mothers were more stable than other family members in CD frequencies, and more so with adoptive mothers of high-risk offspring. CD of mothers and high-risk adoptees was highly consistent in the Family Rorschach, but not between spouses in either of the two conjoint procedures, and not in adoptive control families. These analyses will help clarify the significance and relevance of CD as an environmental variable in families, both with and without putatively vulnerable offspring. Conceptual and clinical implications of the findings will be presented.

USA

Accumulated evidence over the past decade suggests a connection between certain aspects of neurocognition and functional outcome in persons with schizophrenia. Unfortunately, greater precision in defining this relationship has been limited due to the use of global measures of functional outcome that are based on patient self-report or indirect methods of observation. In the present study we examined the relationship between neurocognition and on-unit behavior in a sample of treatmentresistant schizophrenia inpatients using a direct observation method that includes highly specific behavioral categories. The neurocognitive battery included measures of secondary memory, working memory, vigilance, executive functioning, verbal fluency, motor speed and dexterity, procedural learning,

NEUROPSYCHOLOGICAL CORRELATES OF THE PANSS COGNITIVE FACTOR ‘iA. Khanbhai, T.S. Ehmann, G.W. MacEwan, G.N. Smith, S. Altman, S.W. Flynn, W.G. Honer Saint Vincent’s Hospital, 749 West 33rd Avenue, British Columbia V5 W2K4, Canada

Vancouver,

Numerous past analyses show that the PANSS divides into 5 factors, one of which has been termed a ‘cognitive’ factor. Bell et al. compared their own cognitive factor to neuropsycho-

174

logical testing in 147 patients. They found significant correlations with poorer performance on their battery (significance at r > 0.21). This study attempts to replicate these results with the models of Fredrikson, of Peuskins, of Bell, and of White, using a greater number of neuropsychological tests. The prediction is that the factor will correlate with attention, memory, and executive functioning in schizophrenics. In a group of psychotic inpatients (n = 63), Peuskins’ factor shows the greatest number of significant correlations: age, VIQ, WAIS comprehension/vocabulary/arithmetic, and digit span backwards. Only vocabulary tends to correlate with the other 3 cognitive factors. In the schizophrenic subsample (n = 34). a similar pattern of correlations emerges for Peuskins’ factor, but not for the others. Also, schizophrenics’ verbal memory scores correlate only with Peuskins’ and Fredriksons’ models. This study finds that the cognitive factor may be more narrowly defined as related to verbal intelligence and attention. Peuskins’ factor, with only 3 items, appears to offer the greatest clinical utility.

CONTRIBUTIONS OF RESPONSE SPEED AND SEMANTIC MEMORY ORGANIZATION TO CATEGORY FLUENCY PERFORMANCE IN SCHIZOPHRENIA: A PATHFINDER NETWORK ANALYSIS J. Kirkland, J.H. Poole, G.K. Shenaut, B.A. Ober, S. Vinogradov S. F. D VA Medical Center San Francisco, California

and UCSF School 94121, USA

of Medicine,

Disagreement exists as to whether impaired category fluency in schizophrenia is due to access/retrieval dysfunction or to abnormalities in the semantic memory network. In the present study, we explored the relationship of access/retrieval and semantic memory organization to categorical word fluency in a sample of 30 schizophrenic outpatients. Mean choice reaction time (RT) on a semantic, priming lexical decision task and the number of inter-node links (Links) generated from Pathfinder semantic network analysis were used as measures of speed of access/retrieval and complexity of semantic memory organization, respectively. Both RT and Links were significantly negatively correlated with animal category fluency, although RT and Links were not significantly correlated with one another. Together, they accounted for 30%, and for approximately equal amounts of the variance in category fluency. Correlations were unrelated to age, sex, education, or IQ. The negative association between RT and category fluency suggests that generalized slowing of access/retrieval in semantic memory influences fluency performance. The decrease in category fluency performance as the number of semantic network links increases may be related to the effects of lateral inhibition in the semantic network, or it may reflect a diffusion of cognitive resources. These findings suggest that category fluency performance in schizophrenia is related to both speed of access/retrieval and semantic memory organization factors. The independence of these two variables indicates that individuals

with schizophrenia may differ in the neurocognitive underpinnings of their impaired category-fluency performance.

EMOTION RECOGNITION AND ASSOCIATION WITH COGNITION SCHIZOPHRENIA

IN

C.G. Kohler, R.E. Gur, W. Bilker, M. Hagendoorn, R.E. Cur Neuropsychiatry, Pennsylvania,

Department of Psychiatry, University Philadelphia 19147, Pennsylvania, USA

of

Recognition of affect, the facial expression of emotion, is a complex cognitive function and a basic requirement for social interaction. Over the past decade, there has been increasing evidence that emotion recognition may represent a characteristic deficit in schizophrenia. We evaluated the ability for recognition of faces expressing happy, sad and neutral emotional states, as well as age recognition and the association with neuropsychological functioning in patients with schizophrenia (n = 35, M : F = 20 : 15) compared to healthy control subjects (n = 45, M: F = 25:20) of similar age and education. Schizophrenia patients performed worse on recognition of emotion without differential deficit for happy, sad, and neutral emotion, as well as recognition of age (F = 24.00; df = 1,79; p = 0.0001). Break-down according to task and sex of face showed schizophrenia patients to perform more poorly on age and emotion recognition for male and female faces. In particular, female faces with emotional content were more difficult to identify than male faces. In healthy control subjects, emotion and age recognition performances did not show significant correlations with cognitive domains of abstraction, attention, verbal and spatial memory, language and spatial abilities, or fine motoric and sensory functions. In schizophrenia patients, emotion, but not age recognition was highly correlated with attention (r = -0.49, p = 0.002), verbal (r = -0.48, p = 0.003) and spatial (r = -0.57, p = 0.002) memory, and language (r = -0.43, p = 0.01) abilities. These findings indicate that emotion recognition utilizes unique neural substrates and may represent a characteristic deficit in schizophrenia, when compared to healthy control subjects.

RISPERIDONE RESTORES PROCEDURAL LEARNING IN SCHIZOPHRENIA V. Kumari, W. Soni, P.J. Corr, T. Sharma Section of Cognitive Psychopharmacology, Psychiatry, De Crespigny Park, London

Institute SE5 RAF,

of UK

Procedural learning (PL) is a form of skills acquisition in which learning is a function of practice on task, without the need for conscious awareness of learned skills routine. There are indications from pharmacological studies that the use of conventional antipsychotics may account for previously noted

175

deficits in this type of learning in schizophrenia. To examine this possibility, we tested schizophrenic patients (20-65 years old) on stable medication with conventional antipsychotics (n = 11; mean years of illness = 15.36, SD = 7.89) and a new antipsychotic drug with atypical properties, risperidone (n = 9; mean years of i!lness = 11.56, SD = 6.91), and compared them with healthy male volunteers (n =9; 20-50 years old). Compared with healthy controls, PL was found to be significantly (p < 0.001) impaired in patients who were receiving typical antipsychotics, but in patients treated with risperidone, PL was much less impaired and not statistically significant (p = 0.10). Age and years of illness were not correlated with PL. These data suggest that the use of risperidone leads to an improvement in skills acquisition in patients with schizophrenia. The beneficial effect of risperidone may be due to its direct pharmacological actions or to its effects on motivational characteristics of the patients.

CLOZAPINE NORMALISES INFORMATION PROCESSING DEFICITS IN SCHIZOPHRENIA V. Kumari, W. Soni, T. Sharma Section of Cognitive Psychopharmacology, Department of Psychological Medicine, Institute of Psychiatry, London, UK Prepulse inhibition (PPI) of the startle reflex (i.e., a reduction in response to a strong startling sensory stimulus, pulse, if preceded shortly by a weak stimulus, prepulse) is a well validated animal model for the investigation of information processing abnormalities in schizophrenia. PPI is reduced in people with schizophrenia, and in rats, if treated with dopaminejserotonin agonists, N-methyl-D-aspartate antagonists, or reared in isolation. We assessed PPI of the acoustic startle response (prepulse-to-pulse intervals: 30, 60, and 120 ms; PPI expressed as percent reduction of non-prepulse trials) in two groups of schizophrenic patients: (1) on an atypical antipsychotic drug clozapine (n = 11), and (2) on a range of conventional antipsychotics (n = 9), and compared them to a group of healthy volunteers (n = 11). Patients on conventional antipsychotics showed less PPI with 30 and 60 ms prepulse trials than controls. Clozapine-treated patients were not significantly different from controls. These data indicate that clozapine may be superior to conventional antipsychotics in normalising PPI deficits in schizophrenia, presumably due to its pharmacological effects on prefrontal regions of the brain or to its actions on multiple neuroreceptors known to be involved in the regulation of PPI.

DISSOCIATIONS AMONG PRAGMATIC, SEMANTIC, SYNTACTIC PROCESSING SCHIZOPHRENIC G.R.

THOUGHT-DISORDER

Kuperberg, P.K. McGuire, A.S. David

Massachusetts Massachusetts

General Hospital. 02114, USA

VBK Room

821, Boston,

We have previously shown that a group of thought-disordered (TD) schizophrenics are relatively impaired in processing different forms of linguistic context within spoken sentences online. However, a characteristic feature of positive thoughtdisorder is its heterogeneity, as manifested by marked variation between individual patients in the type of speech output produced. Here we take an individual case-study approach to investigate the cognitive deficits underlying this heterogeneity. Of the 12 TD patients tested, 6 were globally insensitive to all types of linguistic violations. Four patients were sensitive to pragmatic violations but not to semantic or subcategorization violations, while 2 were sensitive to both semantic and subcategorization but not pragmatic violations. Intriguingly, none of the patients tested were insensitive only to syntactically-violated sentences, consistent with the idea that thought-disorder reflects a deficit in processing pragmatic/semantic rather than syntactic information. These findings suggest that the relative insensitivity to different linguistic violations demonstrated by the group as a whole cannot be explained simply by a single global impairment in the use of all forms of linguistic context, but that the deficits shown by TD schizophrenic patients are at specific levels of pragmatic and semantic processing.

SOCIAL COGNITION, SYMPTOMS PROFILE, AND QUALITY OF LIFE IN SCHIZOPHRENIA B. Liigdberg,

L.L.

Nilsson,

Departments of Psychiatry Hospitals, Lund University,

J. Eberhard at Lund

and Malmd

University

Sweden

Social behavioral disturbances are prominent in various neuropsychiatric syndromes, including schizophrenia. However, the systematic scientific study of these disturbances is hampered by a lack of clinically useful instruments of measuring their neurobehavioral components, in particular, social cognitive functions. We have recently developed a computer-based system to evaluate the ability of patients to interpret and interact with social situations and to quantify the underlying cognitive functions. This system has been used to evaluate social cognitive functions in 100 outpatients with schizophrenia. These functions were compared with clinical symptoms as measured by (PANSS) and with quality of life variables scored by the patient and health personnel using a number of instruments, The degree of deviance from normal controls in social cognitive functions showed a positive correlation with both the degree of negative symptoms and with the degree of discrepancy between patient and personnel scoring of quality of life, indicating a mediating role of those functions. Details will be presented on the interrelationships of the different variables.

EMOTIONAL DISCOMFORT AND VERBAL MEMORY FUNCTION IN SCHIZOPHRENIA P.H. Lysaker, M.D. Bell, G. T.C.

J. Bryson,

E.C.

Kaplan,

Grieg

Roudebush Indianapolis,

VA Medical Center, 116A, Indiana 46202, USA

1481 West 10th Street,

176

Research has demonstrated that impairments in verbal memory in schizophrenia are linked with psychosocial deficits. Less is known, however, about their relationship to clinical features of illness. This study explores the hypothesis that impairments in verbal memory, particularly forms of memory requiring deeper levels of encoding, are uniquely linked to symptoms of dysphoria or emotional discomfort. Accordingly, we examined the association between concurrent measures of symptoms and verbal memory for 87 subjects with schizophrenia. Measures of positive, negative, cognitive, excitement, and emotional discomfort symptoms were derived from factor scores of the Positive and Negative Syndrome Scale. Verbal memory was assessed using two tests requiring relatively superficial levels of encoding: the Hopkins Verbal Memory Test and Digit Span Subtest; and one test requiring deeper levels of encoding, the Logical Memory subtests I and II. As predicted, multiple regressions controlling for age, education, and attention revealed that poorer performance on logical memory was strongly associated with greater levels of emotional discomfort (r’ = 0.22 and 0.25, respectively), while performance on the Digit Span and Hopkins tests, were weakly related to cognitive symptoms scores (r* = 0.05 and 0.08, respectively). Implications for the conceptualization of verbal memory deficits in schizophrenia are discussed.

COGNITION AND SYMPTOMS PREDICTORS OF COMMUNITY FUNCTIONING

AS

A. Malla, R. Norman, L. Cortese, S. Cheng, K. Diaz, E. McIntosh, T. McLean, A. Rickwood Department 392 South

Oj’Psychiatry, Street- WMCH,

University London,

of Western Ontario, Ontario N6A 4G5, Canada

It has been suggested that level of cognitive functioning, as assessed by formal neurocognitive tests, may be as important or even more important than the symptoms in predicting level of community functioning for patients with schizophrenia. Results of past prospective studies, when carefully examined, do not consistently support this hypothesis. In the current study, the authors used symptom and neurocognitive data to predict subsequent level of functioning in the community. Neurocognitive and symptom data collected as part of an earlier study were used to predict the community functioning of 50 patients with a diagnosis of schizophrenia. Community functioning was assessed by staff of a community mental health program using the Life Skills Profile while blind concerning earlier symptom ratings and neurocognitive performance. Symptoms were more predictive of community functioning than were neurocognitive measures. Disorganization symptoms were generally more predictive of community functioning than were either psychomotor poverty or reality distortion. The results of this study and examination of previous longitudinal studies suggest the importance of using symptom levels after optimal treatment rather than symptoms during acute episodes as predictors of community functioning. They also indicate the

need to evaluate the effects of treatment a separable dimension of symptoms.

on disorganization

as

THE VISUAL PERCEPTUAL ORGANIZATION IN SCHIZOPHRENIC SUBJECTS M. Mazza, A. De Risio, R. Roncone, M. Casacchia Clinic Italy

of Psychiatry,

University

of’L’Aquila.

L’Aquila

67100.

Perceptual organizations of different hierarchical levels are an important aspect of vision. Given appropriate conditions (online measures), higher level/global information is processed faster and more accurately than lower level/local information (Navon, 1977). Attention deficits and abnormality perception may be the core symptoms of negative schizophrenia (Barnett et al., 1992). Schizophrenics have deficits in controlling the size of the attentional focus and show a breakdown of Gestalt perceptions (Mizuno et al., 1998). This disturbance could form the basis of delusional perception (Cutting, 1989). We propose to assess whether the perceptive pattern to attend global information is specifically impaired in people with schizophrenia. We tested this hypothesis in a similar judgment task. Subjects were presented with a deck of cards similar to those used by Kimchi ( 1990). We compared a sample of 20 schizophrenics (DSM-IV; mean of IQ = 102) with 20 normal controls. Our data show that people with schizophrenia prefer local rather than global choices, and such bias is significantly different from normal controls. Furthermore, subjects with negative symptoms have more local choices than subjects with positive symptoms and that difference is significant. From this, we conclude that schizophrenics have abnormal perceptual experiences due to impairment of perceptual organization and attentional processes.

PROBABILISTIC CLASSIFICATION LEARNING IN PEOPLE WITH SCHIZOPHRENIA S.W. McGowan, A.D. Lawrence, E. Bridger, P.M. Grasby, D.J. Brooks, C.J. Bench PET Neurosciences. School of Medicine, London WI2 ONN,

MRC Cyclotron Unit, Imperial College Hammersmith Hospital, Du Cane Road, UK

The striatum has been implicated in a specific form of memory, called ‘habit learning,’ which requires the learning of a consistent relationship between cues and responses. Some theorists have proposed a core role for the striatum in the pathology of schizophrenia, and there is neuroanatomical evidence for striatal abnormalities in this disease. We examined the performance of 12 people meeting DSM-IV criteria for schizophrenia on a task which requires learning associations

177

involving a set of stimuli that are probabilistically associated with either of 2 correct responses. This task has previously been shown to require an intact striatum for normal acquisition. All patients were receiving medication at the time of testing. Symptoms were rated using the Comprehensive Assessment for Symptoms and History (CASH). In contrast to our predictions, patients were able to learn the associations as well as the healthy volunteers, despite showing poorer recall for the details of the task and training session. This suggests that the regions of the basal ganglia that mediate habit learning are spared in neuroleptic-medicated schizophrenic patients. Although there was no correlation between neuroleptic dose and task performance, replication in medication-naive patients is required.

SUSTAINED VIGILANCE

FIXATION AS A MEASURE IN SCHIZOPHRENIA

OF

S. Mednick, Y. Chen, P. Holzman, D. Levy, K. Nakayama Department MA 02138.

of Psychology, USA

Harvard

University,

Cambridge,

Schizophrenics demonstrate impairments in sustainedattention tasks, such as the Continuous Performance Task. Prolonged visual fixation requires maintenance of glaze on a target. We developed four fixation tasks with, and without, distracting backgrounds aimed to assess their potential usefulness as a measure of sustained attention. Eye movements of five schizophrenics and six normal controls were recorded during four fixation tasks (30 seconds each): central target, central target with moving grating background, imagined target with moving grating background, and fixation in total darkness without a target. We analyzed two dependent variable: ( 1) saccade frequency, and (2) velocity distribution as a measure of slow wave drift. Schizophrenics demonstrated a significantly greater number of saccades across all four tasks compared with normal controls. Patients also demonstrated significantly slower wave ocular drift, as measured by the bandwidth of the velocity distribution. Of the four tasks, schizophrenics were most impaired when they were required to fixate on an imagined target with a moving background. These results are consistent with other findings implicating sustained, attentional impairments in schizophrenia. The extended time period of the fixation tasks may be a novel way to measure attentional vigilance.

AXONAL CONDUCTION TIME, CEREBRAL LATERALITY, AND THE ESSENTIAL TRAIT ABNORMALITY IN SCHIZOPHRENIA R. Miller Department Universit?,

of Anatomy and Structural Biology, of Otago. PO Box 913, Dunedin, New Zealand

Much evidence suggests that schizophrenia involves an abnormality of cerebral asymmetry. Some such data relates to psychotic episodes, some to trait abnormalities seen at other times. Theoretical work on this develops from a recent psychobiological theory of normal cerebral laterality (Miller, 1996). It is proposed that the normal left hemisphere has an abundance of slow-conducting cortico-cortical axons, while the normal right hemisphere has a predominance of more rapidly conducting ones. Many trait abnormalities of schizophrenia consist of impairment in right hemisphere type functions. These include poor performance in perceptual and attentional tasks, and symptoms such as impairment in prosody and facial expressiveness. Eye-tracking dysfunction may also represent impaired right hemisphere function. Given this, it is proposed that the biological basis of the schizophrenic trait is loss of rapidly conducting cortico-cortical axons, which potentially applies to both hemispheres, but particularly affects right hemispheretype functions. On this basis, arguments are presented showing that core psychological traits of schizophrenia (widening of associative networks, reduction of cognitive inhibitory processes, reduced ‘processing resources’) can be related to a general preponderance of slow conducting cortico-cortical axons. Further psychophysiological and biological implications (P300, ventriculomegaly, reduced neuronal size) and predictions are discussed.

LATERALIZATION OF WORKING MEMORY, RIGHT HEMISPHERE ABNORMALITY, AND THE DISORDER LANGUAGE AND THOUGHT IN SCHIZOPHRENIA

OF

R. Miller Department University

of Anatomy and Structural Biology, of Otago, PO Box 913, Dunedim. New Zealand

It has been proposed that psychological specializations of the normal right hemisphere depend on its having a richer repertoire of rapidly conducting cortico-cortical axons than the left (Miller, 1996). This gives the right hemisphere superiority in dealing with gestalts, whose elements occur simultaneously (and without fine temporal structure). It is also suggested that loss of rapidly conducting axons underlies trait abnormalities in schizophrenia (Miller, this conference). Recent theoretical work develops these ideas to explain some trait abnormalities of language and thought in schizophrenia. Evidence and theory suggest that speech output has an underlying deep structure independent of grammar and syntax (Chomsky). Evidence from normal subjects suggests that accumulation of meaning, within working memory, over sentences or longer segments of speech is a right hemisphere function. It is proposed that, while grammar and syntax are mainly served by the left hemisphere, the deep structure of speech output is represented mainly by slow-moving ‘gestalts of meaning’ held in the right hemisphere. Given this, the trait disorder of speech output and thought in schizophrenia should consist largely of weakened representation of the underlying deep structure, which holds discourse plans

178

together. Syntactic and grammatical only indirectly and less severely.

structures

are

affected

PUPIL DILATION SUGGESTS REDUCED RESOURCE ALLOCATION IN SCHIZOPHRENIA PATIENTS WITH NEGATIVE SYMPTOMS A.

Minassian,

E. Granholm,

W. Perry

Department of Psychiatry, UC San Diego, La Jolla, California 92093-0804, USA

9500 Gilman

Drive,

Schizophrenia patients are hypothesized to have impairment in processing information during tasks with high processing load. Pupil dilation has been used as a means of assessing the allocation of processing resources. Studies using pupil dilation have supported the hypothesis that schizophrenics have reduced pupil dilation during high processing load tasks, suggesting that they have deficits in resource allocation during complex and demanding cognitive functions. Resource depletion in schizophrenia is thought to be related to the failure of frontal systems to regulate higher-order cognitive functions. Frontal deficits have also been associated with negative symptomatology. To examine these hypotheses, we developed a novel paradigm to study resource allocation during a cognitively demanding task. Fifteen schizophrenia patients and 15 normal controls were presented with the Rorschach, an abstract problem solving tasks, and their pupillary responses were recorded. We found that, across the testing session, pupil dilation was inversely correlated with negative symptom scores for the schizophrenia patients (-0.24 to -0.86). These findings suggest that smaller pupil dilation, thought to reflect reduced resource allocation, is associated with higher negative symptom scores. The association between frontal systems, negative symptoms, and resource allocation will be discussed in relation to schizophrenia patients and normal controls,

THE EFFECTS OF HALOPERIDOL AND LORAZEPAM ON COGNITION AND PROSODIC PROCESSING IN HEALTHY CONTROL SUBJECTS R. Mitchell, M. P.W.R. Woodruff

Barry,

A. Cruttenden,

J.F.W.

G.907, Neuroscience and Psychiatry Unit, Stopford University of Manchester, Oxford Road, Manchester UK

Deakin,

Building, Ml3 9p~,

Studies have reported that the left-taterdhsed cortical response to listening to speech is reversed in schizophrenic patients compared with controls. One possible explanation is that schizophrenic patients over-attend to prosodic, as opposed to semantic, features of language, as prosody is known to activate the right hemisphere more than the left. In order to

test this hypothesis in future neuroimaging studies, we aimed to determine the effect of anti-psychotic medication on performance on a prosody task. Volunteers (n = 16, age 19-39, mean 27.5) received 2-mg haloperidol, 4-mg haloperidol, 2-mg lorazepam, or placebo on 4 separate occasions. Subjects were presented with a series of phrases (happy/sad meaning or happy/sad sounding) and had to identify which either (1) described happy scenes, or (2) sounded happy. Using a repeated-measures general-linear model, there were no significant differences between the 4 treatment groups in number of stimuli correctly identified, number of false positives, and mean reaction time (p > 0.4). Further analyses indicated a strong practice effect for the number of stimuli correctly identified (p =0.014) and mean reaction time (p = 0.074). Therefore, neither haloperidol nor lorazepam modulate attention in healthy volunteers who perform this task. Hence, medication will not be a significant confounding effect when this task is applied to patients with schizophrenia.

MEASUREMENT OF DYSEXECUTIVE SYNDROME IN YOUNG PEOPLE WITH SCHIZOPHRENIA - A CASE STUDY APPROACH E.K.

Newton,

S. Frangou,

T. Wykes

Department of Psychology, Institute of Psychiatry, De Crespigny Park, London, SE5 SAF, UK

Patients with adolescent-onset schizophrenia have shown similar executive functioning problems to those with adultonset schizophrenia. These were measured using non-ecologically valid tasks which have little face validity for everyday skills. This paper reports a case study comparing new ecologically valid (e.g., BADS) vs traditional (e.g., WCST) measures of executive functioning and also investigates the patterns of deficits. Ten cases of adolescent-onset schizophrenia (currently aged 1.5-20 years) were examined. Background factors such as IQ, symptoms, and current social functioning were also measured. The results indicate that all young people with schizophrenia have deficits on the BADS dysexecutive tests. Similarly, on an ecologically valid test of memory, none showed normal performance. Traditional measures of neuropsychological performance showed the same results: poor performance on tests of planning, memory, and cognitive flexibility. Though pervasive difficulties were shown by 7 out of 10 people on the BADS and 8 out of 10 people on traditional executive tests, these showed poor correspondence. Pervasive difficulty on the BADS was related to poor social functioning, whereas pervasive difficulty on traditional measures was related to symptom scores. This suggests that different ways of measuring executive functioning deficits will be related to different types of outcome measure.

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FUNCTIONAL IMBALANCE OF CEREBRAL HEMISPHERES IN SUBGROUPS OF SCHIZOPHRENIC PATIENTS I.A. Nimatoudis, G.S. Kaprinis, A.S. Karavatos, K.G. Fokas, S.G. Kaprinis A’ Psychiatric Department, Neuropsychological Laboratory, Aristotle University of Thessaloniki, Thessaloniki, Greece The purpose of the study was the investigation of the functional imbalance between the cerebral hemispheres in subgroups of schizophrenic patients using a digit dichotic listening test. We studied 70 right-handed schizophrenic patients; 34 paranoics, 18 hebephrenics, and 18 patients with residual schizophrenia (according to ZCD-10 diagnostic criteria for research), and 30 healthy controls with a free-recall dichotic listening test consisting of 20 pairs of three-digit sets. All 3 schizophrenic groups showed a statistically significant greater right ear advantage in comparison to healthy controls (p < 0.001). The 3 patient groups differed statistically significant from each other according to laterality index @ < 0.001) and to right ear performance (p < 0.03), while they had a common overall and left ear performance. The patients with paranoid schizophrenia had a greater right ear performance than the hebephrenic patients (p < 0.03) and the hebephrenic patients had a greater score than the residuals (p < 0.03). From our results, we can hypothesize that that diagnostic subgroups of schizophrenics are characterized by a different activation level of the left hemisphere, which seems to be connected to the productive (positive) psychotic symptoms.

NEUROCOGNITIVE AND ENVIRONMENTAL CONTRIBUTORS TO WORK RECOVERY AFTER INITIAL ONSET OF SCHIZOPHRENIA: ANSWERS FROM PATH ANALYSES K.H. Nuechterlein, K.L. Subotnik, M. Gitlin, M.E. Dawson, J. Ventura, K.S. Snyder, D.L. Fogelson, S. Shaw, J. Mintz Department of Psychiatry, University of California, Los Angeles, 300 UCLA Medical Plaza, Room 2240, Los Angeles, California 90095-6968, USA Recovery of work functioning often lags substantially behind resolution of characteristic symptoms in schizophrenia. We sought to determine through path-analytic procedures the predictors and likely contributors to work outcome in 104 patients who had experienced a recent first episode of schizophrenia. Treatment involved fluphenazine decanoate, behavioral group therapy, family education, and individual case management for a period of 1 year outpatient stabilization. Path model 1 had two latent variables measured at entry, ‘Early Perceptual Processing and Vigilance’ and ‘Hostile Interactions,’

each with two directly measured variables. The Early Perceptual Processing and Vigilance variable and Hostile Interactions variable were found to contribute significantly and independently to prediction of work outcome. One prominent question left unanswered by this first path model was whether the initial level of schizophrenic symptoms played a key role and had a direct relationship to later work outcome that might account for the contributions from the neurocognitive and interpersonal interactions variables. Path model 2 shows that prediction of work outcome is not attributable to initial level of schizophrenic symptoms, but rather the neurocognitive factor and the interpersonal interactional factor play the significant predictive roles. This model has excellent goodness of fit (0.982, adjusted GFI = 0.954).

SIZE AND SHAPE RECOGNITION: ACCURACY AND RESPONSE TIME FUNCTIONS DETERMINED BY THE DISPARITY BETWEEN A REFERENCE TEMPLATE AND A TEST SAMPLE A. Parwani, D.R. Medoff, H.H. Holcomb Maryland Psychiatric Research Center, University PO Box 21247, Baltimore, Maryland21228, USA

of Maryland,

A person will take more time to categorize an ambiguous object than one that clearly belongs to a specific class. By constructing parametric recognition tasks one can determine how much disparity between two objects is necessary to produce a reliable error of various magnitudes. This, in turn, can be used in conjunction with functional neuroimaging to assess how a person’s brain adapts to similar tasks that differ along a single psychophysical attribute. Two forced-choice visual recognition tasks were used to study the recognition accuracy of normal healthy volunteers (n = 8). One task consisted of alternating dark and light lines; the other task required size estimation of a dark rectangle. The former task contained 6 levels of difficulty and the latter contained 8 levels. As the disparity between the reference object and the test object became less, the response time associated with the decision increased significantly @ < 0.05) for both tests. Similarly, the accuracy fell from about 90% to about 60% on both tasks @ < 0.0001). Systematic manipulations of texture and size permit investigators to assess how a person’s decision accuracy and speed change in relation to brain activity patterns. This may be particularly useful in studies of schizophrenia, an illness often associated with abrupt changes in task performance.

NEURAL SUBSTRATES OF BEHAVIORAL ORGANIZATION IN SCHIZOPHRENIA M.P. Paulus, M.A. Geyer, D.L. Braff Department of Psychiatry, University of California La Jolla, California 92093-0804, USA

San Diego,

180

The sequential organization of human behavior comprises the selection and sequencing of individual behavioral elements to form adaptive patterns of behavior. We aimed to determine the factors that contribute to differences in sequential organization of human behavior between schizophrenic patients and controls, using a simple binary choice task. Twenty nine schizophrenia patients and 30 comparison subjects were tested. A 2-choice guessing task was used to obtain sequences of responses from the patients and controls. Subjects are asked to predict where a stimulus will occur that is randomly presented on the left or right side of the screen. The dynamical entropy quantifying the degree of predictability of the sequences was significantly lower in schizophrenic patients compared to controls. The fluctuation spectrum of local dynamical entropies quantifying the variability of the predictability showed an increased dysregulation in patients characterized by more predictable and highly unpredictable subsequences. Three factors were obtained, comprising the degree of win-stay/lose-shift strategy, the degree of l-step predictability of the next choice based on the previous response, and the degree of dysregulation on the choice task. Finally, functional magnetic resonance imaging was conducted while patients and controls were performing the 2-choice guessing task.

A LONGITUDINAL STUDY OF COGNITIVE ABNORMALITIES IN DELUSIONS AT DIFFERENT LEVELS OF INFORMATION PROCESSING E.R.

Peters,

Sub-Department Gower Street,

S. Day,

P.A.

Garety

of Clinical Health London WCIE, UK

Psychology,

U, C. L..

Three tasks were included in this study: negative priming, a probabilistic task, and the pragmatic inference task (PIT). Negative priming is at the interface of preconscious/conscious processing. The probabilistic task measures controlled reasoning processes. The PIT is concerned with implicit attributions, accessing preconscious schema. Seventeen deluded, 18 depressed inpatients, and 20 normal controls had data available at two time points (symptomatic and remitted for the patient groups). At time 1, the deluded sample made up their mind on the basis of less evidence than both other groups on the probabilistic task and were more influenced by disconfirmatory evidence than the normals. No differences were found on the PIT or negative priming at either time point, suggesting that the abnormality in delusions lies at the conscious, reasoning level. When remitted, differences on the probabilistic task disappeared, although this was due to the depressed and normals making up their minds significantly quicker than at time 1, suggesting a practice effect, The deluded remained stable on the data-gathering part of the task, but there was a trend towards normalisation on the probability judgment condition. This supports recent suggestions that the reasoning bias is one of data-gathering rather than probabilistic judgment.

COGNITIVE FUNCTIONING IN SCHIZOPHRENIA: COMPARISON IQ OF YOUNG SCHIZOPHRENIC AND MATCHED CONTROLS J. Peuskens, UC St Jozef; Belgium

M.

DeHert,

V. Christiaens,

Leuvensesteenweg

517, B-3070

OF WAIS PATIENTS

S. Joos Kortenberg,

Using the WAIS-R IQ, we examined 81 schizophrenic patients - 50 males (median age 29.6) and 3 1 females (median age 28) ~ and compared their results with those of a control group matched for sex, age, and educational level. Most of the patients were diagnosed as paranoid (36) or disorganised (30); at testing 35 were hospitalised full-time and 17 part time, and 29 were not hospitalised. Most of the patients were treated with neuroleptics. WAIS IQ of schizophrenic patients (median 106 41-43: loll1 19), was significantly lower than the IQ of the controls (median 118 41-43: 107-127; p
VIEWING STRATEGIES DURING PERCEPTION OF AMBIGUOUS FIGURES IN NORMALS AND DELUDED SCHIZOPHRENICS M.L.

Phillips,

C. Senior,

Department ofPsychological IO3 Denmark Hill, London

AS.

David

Medicine, Institute SE5 8AZ, UK

of Psychiatry,

We examined viewing strategies employed by normal volunteers, and deluded and nondeluded schizophrenics for 3 ambiguous figures depicting 2 different images. A line drawing depicting one of the images in the third ambiguous figure was viewed before presentation in an attempt to bias subsequent perception. In the first 2 figures, in normals and nondeluded but not deluded schizophrenics, the more that features critical for depiction of one of the images were fixated, the greater was the likelihood of that image being reported. Although no subject was biased in subsequent perception of the third ambiguous figure, normals fixated features critical for perception of

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the cued image more than those of the noncued image. These findings suggest that normal perception of an ambiguous stimulus depends upon the fixation duration of features critical for depiction of either image. Biasing may influence viewing strategies of normals more than those of patients. Further investigation of viewing strategies for ambiguous figures will increase understanding of perception of ambiguity in normal and psychiatric populations.

ATYPICAL NEUROLEPTICS: THEIR IMPACT ON COGNITION, SOCIAL FUNCTION, AND RESOURCE UPTAKE IN A SAMPLE OF SCHIZOPHRENIC PATIENTS K.H. Roberts, P.J. Tyson, A.M. Mortimer Department Hull HUIO

of Psychiatry, 6NS, UK

The University

of Hull,

Cognitive impairment in schizophrenia is well documented, with specific deficits shown in memory, executive function, and attention. These processes are considered important for successful social functioning, and in consequence: their remediation has the potential to be of tremendous value in terms of patient outcome. Conventional (typical) neuroleptics have been shown to have minimal impact on cognition in schizophrenic patients; however, the position with the newer atypical neuroieptics is not clear. Recent evidence suggests that the atypicals may have an ameliorating effect on intellectual function, but study into this area is sparse. This is an 18-month, prospective, naturalistic study investigating the effect of atypical neuroleptics on cognition, social functioning, and resource uptake in schizophrenic patients. DSM-IV patients (n = 16) who have just begun their course of antipsychotic treatment (atypical or typical) will be followed up over 3 assessment periods. Baseline measures confirm a relationship between measures of cognition and social functioning. Comparisons of baseline data with 9-month follow up will be presented.

ARE DELUSIONS THE PRODUCT ABNORMAL SEMANTICS?

OF

S.L. Rossell, J. Shapleske,A.S. David Department of Psychological London SE5 8AF. UK

Medicine,

Institute

of Psychiatry,

The study of cognitive deficits in schizophrenia has recently focused upon semantics: the study of meaning. Delusions are proposed as the natural link between abnormal semantics and the psychopathology of schizophrenia: both involve aspects of meaning and belief. Three experimental studies (semantic priming, sentence verification, and semantic fluency) investigated semantic deficits with special attention to how affective stimuli influence semantic judgements. Two well-matched subgroups

of patients with schizophrenia currently deluded and recovered deluded and a normal control group were tested. Briefly, the priming experiment showed reduced, direct semantic priming and intact indirect priming in the deluded subgroup, especially for negative material. Analysis of sentence verification errors demonstrated a bias in deluded subjects to accept improbable sentences congruent with their delusional ideas. Semantic fluency production was significantly reduced in deluded patients compared to nondeluded and an examination of word clusters indicated more idiosyncratic word associations. The overall results are interpreted as showing the disorganisation of semantic shores in schizophrenia, with additional disruption coinciding with delusions. During periods of delusions, the semantic system is prone to aberrant patterns of activation built around the delusional themes; therefore, as delusions are typically emotional or socially salient, emotive material accentuates this pattern. We speculate that the data indicate disorganised storage or semantic information, which in turn interferes with efficient access.

THE FUNCTIONAL AUDITORY-VERBAL

ASYMMETRY OF HALLUCINATIONS

S.L. Rossell, J. Shapleske, P.W.R. Woodruff, AS. David Department of Psychological London SE5 8AF. UK

Medicine.

Institute

of Psychiatry,

Neuropsychological and neuroimaging studies in schizophrenic patients with auditory-verbal hallucinations (AVH) have suggested reduced or even reversed functional asymmetry. This study investigated whether such patients show a reduction in left hemisphere performance using auditory (a standard dichotic listening task), visual (a lateralized lexical decision task) and motor (speed of finger tapping) tests. These tests typically produce a right ear, right visual field, or right hand (left hemisphere) advantage in the normal population. Performance of two groups of schizophrenic patients, those with a history of AVH and those with no such history (NH) were contrasted with a group of normal controls. There were no significant group differences on the lexicon decision task; all grouns demonstrating a right visual field advantage. The AVH patients were con&tentiy slower on the finger tapping test for both hands compared with the other two groups, but they still showed a right hand/left hemisphere motor advantage. The dichotic listening results demonstrated that the NH group had no ear advantage during a free listening condition, while the AVH group showed the normal right ear advantage. However, unlike the NH group, those with AVH showed no ear advantage when attention was directed to the left ear. Additionally, there were no differences according to whether the AVH group was hallucinating at the time of testing. The results suggest that any differences in functional asymmetry in patients with and without a history of AVH may be specific to the auditory modality, and may further be modulated by attentional influences.

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SCHEMA FLEXIBILITY IS DIFFICULT SCHIZOPHRENICS WITH DELUSIONS P. Schaapveld,

FOR

J. Simpson, D.J. Done

Department of Psychology. University College Lane, Hatfield, Herts, UK

of Hertfordshire,

An excessive reliance on ‘top-down’ processing as an aetiological factor in schizophrenic delusions has been proposed by several researchers (e.g., Magaro, 1980). The hypothesis that a delusion acts as an overused schema - a key component in top-down processing - has also been noted by Simpson and Done (1997), who found that delusional schizophrenics tended to interpret ambiguous material according to their own individual delusion. This experiment further investigated problems in the general flexibility of schema use. Schizophrenic subjects with delusions were asked to give explanations for five sentences which, upon first hearing, did not seem to make sense; for example. ‘The prawn cocktail is going to eat the steak next.’ To aid comprehension, three cues were available for each sentence. The comprehension of each sentence depended on the subject’s ability to use the cues’ flexibility to elicit the relevant schemas. A composite score was obtained for each subject. Schizophrenics with delusions performed significantly worse than well-matched controls, and several subjects, despite high IQ scores and good motivation, performed almost at floor. These results are discussed with respect to problems with cognitive inflexibility generally and correlations with similar test measures.

A HYPOTHESIZED PHENOMENOLOGICAL MICRO-GAP (75-200 ms) IN SCHIZOPHRENIA: EVIDENCE AND ALTERNATIVE EXPLANATIONS C. Schooler Section on Socioenvironmental Program, National Institute Maryland 20892, USA

Studies, Intramural Research of Mental Health, Bethesda,

Findings from our experimental psychological investigation of schizophrenia raise the intriguing possibility that schizophrenic individuals have a particular deficit in memory in the range of approximately 75-200 ms, their memory over longer periods being relatively more intact. According to Cowan, the brief sensory store during this 75-200ms period provides continuity to phenomenological experience. If it is impaired, changes may ‘appear suddenly with no fluid motion between them.’ Some such tendency toward successive freeze-frames may more generally characterize the phenomenological experience of some schizophrenic individuals for whom micro-gaps in memory and experience may be a particular characteristic. Such micro-gaps may also impede rapid response when the linkage between the stimulus and response must be refreshed by working memory because different modalities or relatively

unlearned responses are required. Fine motor coordination may also be affected, if the individual is not able to take advantage of proprioceptive feedback occurring within the micro-gap period. Alternative hypotheses suggest that our findings may be explained by less precise stimulus encoding and/or slower cognitive processing speed on the part of schizophrenic compared to normal individuals. This presentation marshals the relevant data and discusses the pros and cons of the micro-gap hypothesis and its alternatives.

NEUROPSYCHOLOGICAL FUNCTIONING AND SUBSTANCE ABUSE IN SCHIZOPHRENIA PATIENTS S. Schwartz, B. Woolwine, R.R.J. Lewine

G. Scheller-Gilkey,

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA

Previous studies have found that between 50 and 65% of patients diagnosed with schizophrenia also have a comorbid substance abuse/dependence problem. Although there have been documented trends in patients with this dual diagnosis, overall neuropsychological findings in this population are inconsistent. However, Scheller-Gilkey, Lewine, Caudle, and Brown found that in a group of patients who abused both alcohol and at least one illicit drug, there tended to be fewer gross brain abnormalities as compared to those patients with no history of substance use/abuse (although not statistically significant). In corroboration with this study, Cleghorn found that drug-abusing schizophrenia patients have neither general nor domain-specific cognitive impairments. Extrapolating from this literature (as well as in an effort to replicate), it is hypothesized that patients with a history of substance abuse will not perform significantly differently on seven neurocognitive domains than will those patients with no history of substance abuse. To analyze this hypothesis, this study will look at 191 schizophrenia/schizoaffective patients who were split into substance-abusing/nonsubstance-abusing groups and then administered tests covering the following neuropsychological domains: language, executive function, verbal memory, spatial memory, visual processing, concentration, and motor function.

HOW VALID ARE CURRENT IQ SUBTEST AND READING SCORES IN ESTIMATING THE PREMORBID IQ OF TREATMENTRESISTANT SCHIZOPHRENIA PATIENTS B. Sheitman, M. Murray, J. Snyder, S. Silva, R. Thompson, M. Chakos, J. Lieberman Department of Psychiatry, University of North Chapel Hill, North Carolina 27614. USA

Carolina,

183

In order to examine how schizophrenia patients differ from normal control subjects on measures of brain morphology and neuropsychological functioning it may be important to ‘match for premorbid intellectual ability. This study examined whether current IQ and reading scores provide a valid estimate of premorbid IQ in treatment-resistant (persistent positive and negative symptoms) schizophrenia patients. School records of 20 patients (mean age 40 [29-571, duration of illness 20 years [ 1 l-34]), with IQ testing taken as part of routine educational assessments, were examined. Testing occurred a mean of 6.4 years (l-15) prior to the onset of psychosis. Current IQ scores were derived from Wechsler Adult Intelligence Scale Revised (WAIS-R) subtests (vocabulary, information, and block design) and the reading subtest of the Wide Range Achievement Test-Third Edition (WRAT-III). Premorbid IQ scores were estimated using: (1) 2 WAIS-R short forms, (2) WRAT-III reading scores, and (3) combined WAIS-R subtests and demographic data used in a ‘bestperformance’ fashion. The correlations with premorbid IQ were 0.77, 0.69, 0.76, and 0.67, respectively. Only the best-performance method did not significantly underestimate premorbid IQ scores. This method may provide the most valid estimate of premorbid IQ scores in treatmentresistant schizophrenia patients. Reference Vanderploeg, of WAIS-R demographic Psychological

R.D., Schinka, J.A., Axelrod, B.N., Estimation premorbid intelligence: current ability and data used in a best-performance fashion, Assess, 1996;8:404-411

A LONGITUDINAL STUDY OF COGNITIVE DECLINE IN CHRONIC SCHIZOPHRENIA J.M. Silverman, M. Parella, R.C. Department Medicine,

P.D. Harvey, Mohs, K.L.

J. Friedman, Davis

L. White,

of Psychiatry, Box 1230, Mt. Sinai School New York 10029. USA

of

Cross-sectional prevalence studies of long-term hospitalized schizophrenic patients show age-related diminishing cognitive functioning unrelated to other known causes of dementia. Nevertheless, the existence of a subgroup of patients with latelife, schizophrenia-related, cognitive decline remains controversial. For more than five years our center has been prospectively assessing chronic schizophrenic patients with long-term hospitalization for changes in global cognitive impairments using the Clinical Dementia Rating scale (CDR). At present, of 1103 elderly schizophrenic patients entered into our longitudinal study, 457 (mean age = 71 * 12 years) had no more than mild symptoms of global cognitive impairments (CDR score < 1.0) at baseline assessment. This group has now been followed for up to 60 months and has had up to 3 follow-up assessments of their cognitive functioning over this period. Survival analysis was used to examine the proportion of these patients who show a clear-cut worsening in cognitive functioning over time; i.e., an increase in CDR score to at least 2, indicating moderate or

more severe symptoms of dementia. After 15 months, approximately 17% + 2% showed cognitive decline. The cummulative risk rose to 34% k 3% after 46 months, and 51% k 5% after 60 months. Initially, less-impaired patients with less than the median years of education (< 10 years) had a significantly greater risk of cognitive decline than those at or above the median (X2 = 8.65, df = 1, p < 0.005). In addition, patients below the median age ( < 71 years) showed, at a marginal level of statistical significance (X2 = 3.44, df = 1, p = 0.06), a lower risk of cognitive decline than those at or above the median. The results agree well with earlier results obtained in a smaller subgroup of patients (n = 160) over a shorter period and indicate substantial risk of cognitive decline among elderly, hospitalized, chronic schizophrenic patients.

CONTOUR INTEGRATION SCHIZOPHRENIA S.M. Silverstein, S. Nuemberger

R. Corry,

IN

K. Nghi&m,

C. Valone,

Department of Psychiatry, University of Rochester Center, 300 Crittenden Boulevard, Rochester, New USA

Medical York 14642,

Previous research has noted relationships between perceptual organization impairments and disorganized thinking and symptoms in schizophrenia, suggesting that this disorder is characterized by a dysfunction in a common cortical processing algorithm involving contextual coordination. One hypothesized manifestation of deficient contextual coordination is impaired contour integration, as has been previously demonstrated in amblyopic patients. In this study, we are assessing contour integration in schizophrenia and age-matched psychiatric and nonpsychiatric controls. Contour integration is assessed by examining subjects’ ability to identify closed contours in fields of Gabor patches with various degrees of grouping strength. Preliminary data indicate that chronic schizophrenia patients (n = 17) have poorer contour integration abilities compared to other chronic psychiatric patients (n = 12) and normal controls (n = 16). In addition to describing an expanded data set, we will describe relationships between contour integration ability, disorganized symptoms, and disorganized aspects of formal thought disorder.

SCHIZOPHRENICS WITH DELUSIONS SHOW IMPAIRMENTS IN COGNITIVE TRANSFER J. Simpson,

D.J.

Done

Department of Psychology, University College Lane, HatJield, Herts.. UK

of Hertfordshire,

Reasoning is not a homogenous ability, and the search to find a stable, isolable reasoning deficit as an explanation for

184

the aetiology of schizophrenic delusions is untenable (Simpson, et al., 1998). Different reasoning styles make differential use of more-central cognitive abilities. For example, syllogistic reasoning is particularly working-memory intensive. It is possible that in patients with delusions, deficits in a particular type of reasoning ability might occur where such reasoning depends on specific, limited cognitive abilities. Analogical reasoning, or ‘transfer’ exerts a considerable load on several cognitive abilities, including the search for an appropriate analogue (Novick, 1998). Shortcomings in effective search strategies have been shown in several studies using schizophrenic subjects (Simpson and Done, 1997), and it is hypothesised that these problems might underpin potential difficulties with effecting cognitive transfer. Using the analogical reasoning paradigm developed by Gick and Holyoak (1983), schizophrenic subjects with delusions were asked to solve a problem after having being given an analogous problem and its solution. Compared to well-matched controls, schizophrenics with delusions performed significantly worse. The results are discussed in relation to problems with cognitive flexibility and ineffective search mechanisms.

SUPPRESSING IRRELEVANT AND DELUSIONAL THOUGHTS IN DELUDED AND NON-DELUDED SCHIZOPHRENICS J. Sinclair, K.R. Laws, P.J. McKenna Department of Psychology, University of Hertfordshire, College Lane, Hatfield, Herts AL10 9AB, UK

We compared the ability of 6 deluded and 6 nondeluded schizophrenics to suppress specific thoughts. Patients were first asked to talk/think about anything for 3 minutes, followed by 3 minutes in which they could talk/think about anything except ‘white bears’ (suppression condition), then 3 minutes in which they could talk/think about anything (including white bears, if they wanted). In a second phase using the same paradigm, the patients were asked to suppress thoughts relating to the specific delusional content of the deluded patients (e.g., you can talk about or think about anything except ‘the Queen’. All verbal material was recorded, and patients were asked to press a buzzer if they thought about these topics (i.e., fleeting thoughts). Normal subjects typically find it difficult to avoid thinking about topics when asked not to and also show a ‘rebound’ effect in the last phase (i.e., frequently thinking about white bears). Deluded and nondeluded patients showed no differences in the ability to suppress thoughts in either topic conditions. Indeed, they showed a form of super-suppression showing no evidence of the typical rebound effect. This study suggests that delusions are not ‘pressing’ thoughts that patients would have difficulty in consciously suppressing.

A SCALE TO MEASURE SUBJECTIVE WELL-BEING FOR OUTPATIENTS WITH SCHIZOPHRENIA C.E. Sison, E. Allan, M. Alpert VA Hudson New York,

Valley Health 10548, USA

Care System,

PO Box 100, Montrose.

This scale was rationally generated by the therapist and outpatients in a weekly schizophrenia psychotherapy group. Their objective was to develop a monitor subjective correlates of improvement. The scale consisted of 18 Likert-type and 5 frequency items. It is completed weekly. Psychometrics were derived from 464 questionnaires. Principal components analysis revealed one main factor, social adjustment and optimism, which accounted for 50% of the variance, and two other minor factors. Cronbach’s Alpha was 0.94 on this factor, suggesting a highly coherent scale. Test-retest reliability from 11 subjects was r = 0.90, p < 01. Sensitivity to patient’s state was done by computing correlations with outcome measures of psychopathology, side effects, and time since discharge, using pilot data from 9 patients. Results suggested that a higher score in Good Signs correlated with lower EPS (r = -0.71, p = 0.05), akathisia (r = -0.79, p = 0.02), and a trend with PANSS Positive Symptoms. Patients report that completing the form every week helps them focus on how well they are doing. This scale is reliable and potentially may be a valid outcome measure of subjective well-being for schizophrenic outpatients. Sensitivity to side effects ratings suggests usefulness for other groups such as the elderly and other psychiatric diagnoses.

ROLE OF TARGET SALIENCE AND TASK DIFFICULTY IN VISUOSPATIAL CUEING OF ATTENTION: IMPLICATIONS FOR CLINICAL POPULATIONS R. J. Snowden, J.L. Muir, J.C. Willey School Wales,

of Psychology, UK

Card@

University,

Cardiff

CFI

3 YG,

Attentional problems in many clinical populations, including schizophrenia, have been probed using a visuospatial cueing paradigm. Here a cue is presented that predicts, the likely location of a forthcoming target. If the target is presented at this location, subjects are faster and more accurate than if the target is presented at the alternative location. However, little is known as to how (1) the salience of the target, or (2) the difficulty of the task might govern the size or presence of cueing effects. We manipulated target salience by varying the contrast of the targets, and we manipulated task difficulty by varying the difference in orientation between the two targets that needed to be discriminated. We further investigated the effect of blocking or interleaving these manipulations.

185

Using blocked designs we obtained a large effect of target contrast upon the size of the spatial cueing effect, and we obtained small but significant effects of task difficulty. Using an interleaved design we still found large effects of target contrast but no effect of task difficulty. Therefore one must ensure that early visual problems that might change target salience are corrected when comparing population on such tasks.

NORMS FOR USE WITH COGNITIVE ASSESSMENT OF PEOPLE WITH SCHIZOPHRENIA R. Stewart Colorado Mental Pueblo, Colorado

Health Institute, 81003. USA

1600 West 24th Street,

When psychologists are asked to perform cognitive assessments of people with schizophrenia, common referral questions relate to the degree of cognitive strengths and deficits in relation to other people with schizophrenia. The purpose of this paper is to review norms in the literature available to answer such referral questions. Where feasible, subgroups are listed by age and education and may include meta-analytically derived means and SDS for test scores. For example, for Trails B, 9 separate groups with schizophrenia were found (total n = 482). While the mean score across all groups was 130 seconds (SD = 100) (age = 40, education = 12, 70% inpatient), subgroups had mean scores ranging from 14 seconds to 293 seconds. The tests reviewed include: Controlled Oral Word Association (animals), Controlled Oral Word Association (FAS), CVLT, Hooper Visual Organization test, Mattis Dementia Rating Scale, Mini-Mental State Examination, Neurobehavioral Cognitive Status Examination, Rey auditory verbal, Rey complex figure, Rey 15-item malingering, Trails A, Trails B, WAIS-R, WCST, WMS-R.

COMMUNICATION DEVIANCE IS ASSOCIATED WITH PUTATIVE GENETIC VULNERABILITY INDICATORS IN RELATIVES OF SCHIZOPHRENIA PATIENTS K.L. Subotnik, K.H. Nuechterlein, R.F. Asarnow, M.J. Goldstein, D.L. Fogelson, R.D. Torquato Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 300 UCLA Medical Plaza. Rom 2239, Los Angeles, California 90095-6968. USA

normal controls and may be a subtle manifestation of some genetic vulnerability relevant to schizophrenia. This is supported by evidence that thought disorder is correlated with neurocognitive deficits that are putative genetic vulnerability indicators in schizophrenia patients, and CD in parents is associated with vulnerability indicators in their schizophrenic offspring. We directly examined whether CD in 73 nonpsychotic biological parents of recent-onset schizophrenia patients was correlated with Span of Apprehension or Continuous Performance Test anomalies in these same parents. One of the two CD factors hypothesized to be related to neurocognitive deficits, Factor 2, ‘Misperceptions,’ was associated with poor early perceptual encoding on the Span in parents (12-letter Y = -0.27, p < 0.03; 5-letter arrays, Y = -0.41, arrays, p < 0.0003). Degraded Stimulus CPT signal/noise discrimination was not significantly associated with either CD factor. These findings support the view that subclinical thought disorder and early perceptual encoding share some variance as indicators of a potential vulnerability factor in schizophrenia.

SEX STEROIDS AFFECT COGNITIVE PERFORMANCE IN WOMEN WITH PSYCHOSIS K. Thompson, A. Sergejew, J. Kulkarni Monash University Research Centre for Women’s Health, Dandenong Area Mental Health Service, Dandenong, Melbourne, Victoria 3175, Australia

Mental PO Box 956,

This study combines current work on the estrogen hypothesis, which postulates that estrogen raises the vulnerability threshold in women with schizophrenia, with the work of Hampson (1990a, 1990b), that found that sex steroids affect cognitive ability in normal women. The main aim was to extend Hampson’s (1990a, 1990b) work and investigate whether sex steroids affect cognition in women with psychosis. The sample consisted of 63 premenopausal women, 31 of which were normal controls and 32 who had been diagnosed with a psychotic illness. The results indicated that both the control group and the women with psychosis performed better on male-oriented tasks, particularly the Mental Rotation Test (MRT), when estrogen was low. However in regard to the articulatory-motor tasks, the control showed improved pcrformance when estrogen and progesterone levels were high, whereas the reverse was true for the women with psychosis. These results agree with those of Hampson (1990a, 1990b), bar the unexpected contradictory results concerning motor performance in the psychotic group, which may be postulated to be related to their disease process.

PARSING CONTEXTUAL INSENSITIVITY IN SCHIZOPHRENIA THOUGHT DISORDER D.A. Titone

Communication Deviance (CD), a measure of subclinical thought disorder expressed in speech, has been observed more frequently in parents of schizophrenia patients than parents of

Psychology Research Laboratory, Harvard Medical School, Boston,

McLean Hospital and Massachusetts 02478, USA

186

A failure to represent contextually relevant information has been proposed as an explanation for many of the thought disturbances observed in schizophrenic cognition (Cohen and Servan-Schreiber, 1992). For example, schizophrenic adults consistently misinterpret ambiguous words (pen) when contexts bias their less frequent meanings (animal enclosure but not writing implement) (Chapman et al., 1964). Such contextual insensitivity, however, could result from failures in detecting contextually relevant information and/or inhibiting contextually irrelevant information. Based on work demonstrating intact automatic semantic priming in schizophrenia but impaired inhibitory function, we hypothesize that inhibition failures are the primary mechanism of schizophrenic contextual insensitivity. We tested this using a semantic priming task. Schizophrenic and healthy participants listened to sentences differing in how strongly they biased the less frequent meaning of ambiguous words. Visual targets, semantically related to either meaning (pig or paper) were presented for a lexical decision response. Results indicate that inhibition of contextually irrelevant meanings was significantly more impaired than facilitation of contextually relevant meanings in schizophrenia. A failure to represent contextually relevant information, therefore, is not entirely responsible for contextual insensitivity in schizophrenia. This implies that deficits in schizophrenic cognitive-linguistic behavior should be most pronounced when successful comprehension requires an inhibitory component.

TIME SERIES MODELS SYMPTOM VARIATION SCHIZOPHRENIA

OF DAILY IN

W. Tschacher, Z. Kupper University Psychiatric Services, University Laupenstrasse 49, 3010 Bern, Switzerland

of Bern,

The temporal evolution of symptoms was studied in a sample of young schizophrenia patients. This study elaborates on recent findings concerning the dynamical disease concept of schizophrenia. The present sample consisted of 54 residents of the ‘Soteria’ clinic in Bern (60% males; mean age 25.9 years; mean duration of observation 88 days; mean previous admissions 3.3). Using a rating scale composed of 9 subscales for various positive, negative, and general symptoms, mental status was assessed on a daily basis. Thus, the symptom course for each patient was mapped throughout the period of hospitalization. Principal component analysis of all ratings (n > 5000) yielded evidence of 3 independent factors (‘psychoticity’, ‘excitement’, ‘withdrawal’). In each course we then fitted a time series model of the lagged interrelations between factors using the state space approach. The impact of these interrelations was quantified by parameters. A great variety of significant timelagged interrelations between schizophrenia factors was found. Therefore, subgroups were distinguished by cluster analysis showing that 5 dynamical patterns existed in this sample. These clusters were associated with outcome measures (e.g., in the cluster performing best, withdrawal tended to ‘damp out’ psychoticity, whereas in the most unfavorable cluster, with-

drawal preceded psychoticity. These results are consistent with findings on the long-term evolution of schizophrenia. Our conclusion is that daily measurement and modeling provides an appropriate and clinically accessible window on the psychopathological processes of this disorder.

PATIENTS WITH SCHIZOPHRENIA THEIR VIEW ON CARE

AND

G. Van Humbeeck, Ch. Van Audenhove, G. Storms, M. De Hert, J. Heyrman, J. Peuskens, G. Pieters, H. Vertommen LUCAS,

Kapucijnenvoer

35.3000

Leuven.

Belgium

In research reviews, the following areas in MHC are identified as contributing to successful outcome and to prevention of relapse for patients with schizophrenia: support in social relations, practical aid, treatment and monitoring of evolutions in the illness, information to patient and family members, and coordination and continuity of care. In this research project, the questionnaire ‘View on key elements’ from Shepherd et al. (1994) was translated and adapted to be used as an instrument to assess the patients and professional caregivers perspective. The degree of realisation and the degree of importance of the different areas in care in both perspectives are measured. The aim of this study is to compare the view of care of patients with schizophrenia with patients with a diagnosis of substance abuse or mood disorder. Our data show that in the patients perspective, there are no differences between the diagnostic groups. In the perspective of professionals, however, some differences were found. From this, we conclude that although the sense of reality might be more disturbed by patients with schizophrenia, they share the same view on care as other patients. The only differences exist in the view of professionals. In the future, these differences can be examined.

HOW ARE SELF-EFFICACY, NEUROCOGNITION, AND NEGATIVE SYMPTONS RELATED TO COPING RESPONSES IN SCHIZOPHRENIA? J. Ventura, K.H. Neuchterlein, M.J. Gitlin, J. Sharou

K.L. Subotnik,

Department of Psychiatry and Biobehavioral Sciences, University of California. Los Angeles 300 UCLA Medical Room 2243, Los Angeles, California 90095-6968, USA

Plaza,

Although stressful life events can be ‘triggers’ of symptom exacerbation in schizophrenia, not all patients who experience stressors subsequently relapse. Better neurocognitive performance (Pallanti et al., 1997) and positive self-efficacy, but not negative symptoms (Macdonald et al., 1998), have been associated with the use of problem-focused coping strategies that lessen the stressful impact of negative events. Using the Coping

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Responses Inventory (Moos, 1986) we examined how 25 recentonset schizophrenia outpatients and 16 demographically matched normal subjects responded to a negative interpersonal life event. Cognitively oriented problem-focused approaches (e.g., ‘Making a plan of action and following it’) were used significantly more often by normal controls (M = 2.17) than schizophrenia patients (M = 1.69; p < 0.001). Among schizophrenia patients, those with high self-efficacy used more active problem-focused strategies (r = 50, p < O.Ol), including problem-solving (r = 0.58, p < 0.01). Better performance on a measure of sustained attention and early perceptual processing was also associated with the use of problem-focused coping strategies, such as logical analysis (r = 0.40, p < 0.05) and positive reappraisal (r = 0.40, p i 0.05). Multiple regression indicated that the self-efficacy and neurocognitive variables, but not negative symptom severity, predicted active coping. Differences in the way schizophrenia patients and normal controls cope with stress may be mediated by neurocognitive abilities and self-appraisal factors, but not negative symptoms.

ALLOCATION OF PROCESSING RESOURCES DURING THE BACKWARDMASKING TASK IN OLDER PATIENTS WITH SCHIZOPHRENIA S.P. Verney, E. Granholm, D.P. Dionisio SDSU/lJCSD Joint Doctoral Program in Clinical 6363 Alvarado Court., Suite 103, San Diego, California 92120-4913, USA

COMMUNICATION STABLE TRAIT

DEVIANCE

AS A

K.E. Wahlberg, L.C. Wynne, P. Keskitalo, I. Lahti, J. Moring, M. Naarala, A. Sorri, P. Tienari Department Finland

of Psvchiatry.

University

of Oh,

FIN-90210

Oulu,

Communication Deviance (CD) measures the degree to which a person does not maintain and share foci of attention when communicating with other persons. When CD is found with high frequency in rearing parents of adoptees at high genetic risk (from schizophrenic adopting-away mothers), adoptees show evidence of increased subsyndromal thought disorder. Thus, CD may be an important environmental variable in interaction with genetic risk. However, its hypothesized importance derives in part from evidence that it has enduring status as a stable trait, not as an acute stressor. The stability of CD over time has been evaluated previously in only one study, by Velligan (1995). In this report from the Finnish Adoptive Family Study of Schizophrenia, CD was measured twice, with an 11-year interval, for 92 persons by using tape-recorded, transcribed, individual Rorschach tests. The test-retest correlation was 0.58. There was no difference between sexes in the stability of CD. Further results will be presented on the psychometric qualities of CD, including study subgroups of CD categories and their overlap and differences with the categories of the Thought Disorder Index. These studies will help clarify the details of genotype x environment interaction that have been possible in the Finnish Adoption Study.

Psychology

One of the most replicated findings in cognitive studies of schizophrenia is the impairment exhibited at longer interstimulus intervals (ISI) during the backward-masking (BM) task. Researchers have suggested processing resources devoted to the mask interfere with target processing at longer ISIS. In this study of older schizophrenia patients (n = 11) and normal controls (n = 1 1 ), pupillary dilation was recorded during a BM task (ISIS of 33, 50, 83, 117, and 300 msec, along with a no-mask condition) as a measure of resource allocation with larger dilation reflecting greater allocation of resources. Older schizophrenia patients demonstrated the classic backwardmasking pattern found in younger patients, differing most from normal controls at the longest IS1 (300 msec). Consistent with our previous study of university students, both groups showed more dilation in the 300 msec IS1 than in the no-mask condition, indicating that the mask demanded resources for both groups. The schizophrenia patients showed smaller pupil dilation (allocated less resources) overall, especially in the 300 msec IS1 condition. These findings suggest that the patients with schizophrenia. had fewer resources spared for target processing when resources were allocated to the mask in the 300 msec IS1 condition.

COGNITIVE DYSFUNCTION AND CLINICAL COMPLAINTS IN SCHIZOPHRENIA K.M. Weiss Schizophrenia Ohio, 10000

Clinic JIB(B), Veterans Healthcare System of Brecksville Road, Cleveland, Ohio 44I41, USA

Persons with schizophrenia often display both a lack of insight, indicated by low subjective symptom distress, as well as significant cognitive deficits. The purpose of this study was to examine if the lack of insight is specific to clinical symptoms, or if it pertains to cognitive aspects of the disorder as well. Subjects: All the subjects, 52 men and 2 women, were receiving antipsychotic medication, and were patients in the Schizophrenia Outpatient Clinic. Mean age was 44 years (SD = 8.3, range, 25-66). Method: All the subjects were given the Symptoms of Schizophrenia (SOS) inventory, a 30-item self-report questionnaire. Just prior to the administration of the SOS Inventory, each subject was given an identical pairs version of a continuous performance task (CPT). Results: There was no relationship between the CPT performance and the extent to which subjects reported cognitive or

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clinical symptom distress. There was, however, a strong positive relationship correlation between reporting cognitive and clinical symptom distress. Discussion: Subjects who show poor attention and working memory skills are not more likely to have complaints of cognitive symptoms. Cognitive dysfunction manifested by the CPT in persons with schizophrenia appears to exist independently of clinical distress.

COVERT VISUOSPATIAL SCHIZOPHRENIA

ATTENTION

IN

in the medicated employed.

patients

if appropriately

sensitive

tests

are

INCIDENCE OF STARTLE PREPULSE INHIBITION DEFICITS IN SCHIZOPHRENICS K.A. Young, M. Smith, W. Clark, P.B. Hicks, I.S. Russell Neuropsychiatry Science Center,

Research Program, Ware. Texas 76711.

Texas A&M USA

Health

J.C. Willey, N.S. Gray, R.J. Snowden The CasweN Wales, UK

Clinic,

Glanrhyd

Hospital,

Bridgend

CF314LN.

Attentional processes are thought to be impaired in schizophrenia. Using a visuospatial cuing paradigm, it has been shown that patients are particularly slow to respond to targets presented in the right visual field after being cued to the left. This is true for nonmedicated patients; however, neuroleptic medication abolishes the effect (Wigal et al., Neuropsychologia, 1997;35:1519-1525). By manipulating the luminance of the target, thereby reducing its alerting effect, we hoped to show a similar attentional asymmetry in medicated patients. Subjects detected or identified simple line targets that followed visuospatial cues which either correctly predicted the target’s location (valid) or misled them (invalid). Targets of low and high luminance were tested on a group of medicated schizophrenics and age-matched controls. For high-luminance targets no asymmetries were found. For the low-luminance targets, the schizophrenic patients showed large deficits for targets in the right field after cueing to the left, These results demonstrate that attentional deficits still exist

It has been hypothesized that startle prepulse inhibition (PPI) deficits might indicate a state of ‘sensory overload’ in schizophrenics, which could induce core cognitive and clinical signs. We wondered whether clinical and cognitive deficits would be elevated in schizophrenics with startle PPI deficits. Although the mean PPI ratio was significantly elevated in the schizophrenic group (n = 52) compared to normal controls (n = 28), as previously reported, there was a relatively high incidence of normal PPI among the schizophrenic subjects. For instance, 25% had PPI ratios lower than the control mean (‘normal’ PPI). Schizophrenics classified as expressing abnormal levels of PPI by several definitions did not differ from schizophrenics with ‘normal’ PPI with respect to positive, negative, thought disorder, or other PANSS symptoms; by performance on the Wisconsin Card Sorting or Continuous Performance (CPT) Tests. Changes in positive symptoms, though disorder, and paranoia over time were directly correlated with changes in CPT errors of commission, but not with changes in PPI. The data bring in question the interpretation of startle PPI in animal models as a homologous behavioral assay with special significance to schizophrenic symptomatology.