Neuropsychology

149

VII. Neuropsychology VII.A. Localization of Function VII.A. Oral 1 NEUROANATOMICAL CORRELATES OF AUDITORY EVENT-RELATED POTENTIAL ABNORMALITIES IN SCHIZOPHRENIA P.B. Ward, C. Loneragan, B. Liebert, S.V. Catts, P.T. Michie 2, S. A n d r e w s 1, N. M c C o n a g h y

Schools of Psychiatry and 1Psychology, University of New South Wales, Princeof WalesHospttal, High St, Randwick, NSW 2013, Australia, ZSchool of Behavioural Sciences, Macquarie University, NSW 2109, Australia. This study aims to assess the functional significance of subtle neuroanatomical changes in temporal lobe neuroanatomy frequently reported in post-mortem and neuroimaging studies of schizophrenic patients. Converging evidence from magnetoencephalography, lesion studies and dipole source modelling suggests that event-related potential (ERP) measures that have previously been found to be altered in schizophrenic patients (Ward et al., 1991; Shelley et al., 1991) are generated in part by sources in primary auditory cortex and surrounding association areas in the posterior superior temporal gyrus. In the present study auditory ERP measures which index pre-attentive (mismatch negativity) and attentional (Nd and P300) processing were recorded. 3D volumetric MRI scans were obtained, and temporal lobe structures visualized and measured using the BRAINS package developed at the University of Iowa (N.C. Andreasen et al.). Subjects also complete a battery of neuropsychological tests, including the Wisconsin Card Sorting Test, the Relational Concepts Factor scale of the Luria-Nebraska Neuropsychological Battery, tests of orthographic and phonological processing, the WAIS Block Design and Digit Span subscales and the Peabody Picture Vocabulary Test. Patients, all of whom meet DSM-III-R criteria for schizophrenia and are completely right-handed, are rated using the SAPS and SANS, and a neurological soft signs examination completed. Complete data from 12 stable outpatients have been obtained and will be compared with age-, sex- and handedness-matched healthy controls.

VII.A. Oral 2 THE NEURAL SUBSTRATES OF ANTISACCADE PERFORMANCE IMPLICATE OCULOMOTOR CIRCUIT DYSFUNCTION IN SCHIZOPHRENIA G.A. O'Driscoll, N . M . Alpert, S. Matthysse, D. Levy, P.S. H o l z m a n

Harvard University, Department of Psychology, 33 Kirkland St., Cambridge, MA 02138, USA Increasing interest in the role of the frontal lobe in schizophrenia has generated interest in the antisaccade task, on which both frontal lobe patients and schizophrenics are impaired despite their normal performance on 'pro-' saccade tasks. We used positron emission tomography (PET) to investigate the functional neuroanatomy of antisaccade in normals, and found that the areas of the brain more active during antisaccade than saccade performance were highly consistent with Alexander's (1986) postulated oculomotor circuit, including primary motor cortex, frontal eye fields, supplementary motor area, thalamus and, potentially, putamen. In contrast, activation of area 46 in prefrontal cortex was not found, nor was activation of caudate, which receives projections from this area. The antisaccade's requirement to inhibit the competing reflexive saccade and to 'will' the antisaccade has linked this task, intuitively, to the prefrontal part of the frontal cortex in frontal and schizophrenic patients. However, our data suggest that it may not be prefrontal circuits and executive function, but precentral cortex and motor programming, that may be involved in the performance decrement of these populations. Such a conclusion is consistent with the findings of several studies of non-human primates that have reported that it is premotor neurons rather than prefrontal that differentiate between conditions in which the instructional significance of a stimulus changes while its characteristics remain the same.

V I I . A . P o s t e r 116, O r a l 3 IMPAIRED FRONTAL LOBE FUNCTION SCHIZOPHRENIA IS FAMILIAL

IN

J.S.E. Hellewell, J.F.W. D e a k i n

Univ. Dept. Psychiatry, Rawnsley Bldg., MRI, Oxford Rd, Manchester M13 9WL, UK To determine whether neurochemical abnormalities in postmortem schizophrenic orbital frontal cortex and anterior temporal lobe [1,2] have a genetic basis, we probed the functioning of these regions using neuropsychological and eye movement tests in familial schizophrenics (n > 60), their unaffected relatives (n > 50) and unaffected controls (n > 30). Schizophrenics were markedly impaired in the anti-saccade paradigm which requires saccades in the opposite direction to

150 the movement of a target light. Their relatives showed a bimodal distribution of performance with some performing normally and some as poorly as the schizophrenics (mean % errors schizophrenics=60% trials, controls=18%, relatives=33%). This task requires intact frontal lobe function. Schizophrenics were impaired on other tests of frontal lobe function including verbal fluency, cognitive estimation, trail-making, verbal and non-verbal sequencing. They performed poorly on tests of temporal lobe function: verbal and non-verbal learning, recall and recognition (Coghlan; Squires). On the Warrington Facial Recognition Task more than a third of schizophrenics had scores below the least of the control scores. In addition to impaired anti-saccade performance, relatives showed significant impairments on verbal fluency, sequencing and trails but they were not impaired on tests of temporal lobe function. We propose that the endophenotype for schizophrenia is disordered development of frontal cortex while an additional process affecting temporal lobe function is necessary for manifestation of the psychosis. 1. Deakin et al. (1989) J. Neurochem. 52, 1781-1786. 2. Simpson et al. (1992) Schizophr. Res. 6, 133.

V I I . A . P o s t e r 117 STROOP EFFECTS IN SCHIZOPHRENICS AND CONTROLS: EVIDENCE OF INCREASED INTERFERENCE AT THE INTERHEMISPHERIC LEVEL

VII.A. Oral 4 DIASCHISIS

IN SCHIZOPHRENIA

V. Di Michele, M. Casacchia

University of L'Aquila, Dept. of Psychiatry, L'Aquila, Italy Twenty four DSM-III schizophrenic patients were assessed by a neuroanatomical and neuropsychological evaluation (by Luria Nebraska Neuropsychological Battery). Both Temporal Lobes were found to be reduced by MRI. Schizophrenic patients were divided according to their neuropsychological profile as Abnormal (n= I0) and Normal (n= 14). Both groups were similar in term of age, age at onset of the disorder, educational level, number of hospitalization, symptoms severity (as assessed by BPRS) and phenomenological features (paranoid vs. non-paranoid). Interestingly the group with the abnormal profile showed a marked reduction of temporal lobe areas (two way mixed ANOVA: F(1,22) 7.2, p < 0.05). The implication of our findings is that an anatomical abnormality located at the level of temporal lobes is not associated with psychopathologic and phenomenologic features, but is associated with a global cognitive impairment affecting a broad range of mental ability even though not directly related to temporal lobe function. The interpretation of our findings lend us to re-evaluate the conceptual framework of diaschisis, for the first time in schizophrenia, coined in 1913 by Von Monakow, whose statement may be reformulated as follows: a single dysfunctional area site located in the temporal lobes may produce, through the neural network connected to it, a global cognitive dysfunction involving a broad range of mental abilities.

M.L. Phillips, A.S. David, P. W o o d r u f f Granted by C.N.R., FATMA Project, N.93-00615-PF41.

Maudsley Hospital, Denmark Hill, London, SE5 8AZ, UK Increased Stroop effects have been demonstrated transcallosally in schizophrenia. An attempt was made to replicate and clarify this finding. A divided-field technique for presentation of Stroop stimuli was employed to investigate interhemispheric function in right-handed, male, chronic schizophrenics and age-matched normal controls. Stimuli consisted of a vertical colour strip and colour-congruent, -incongruent or -neutral word. Stimuli were presented tachistoscopically centrally and to right and left visual fields (lateral). Schizophrenics demonstrated significantly greater reaction times (RT) in colournaming compared with controls for central but not lateral presentations. RT correlated with BPRS scores for controls only. The combined Stroop effect (CSE: RT difference between incongruent and congruent conditions) was significantly greater for central compared with lateral presentations in both groups. Further analysis of the central CSE revealed a significantly greater difference in RT between incongruent and neutral pairings compared with neutral and congruent pairings - - a difference not found for lateral CSEs. The results suggest increased interference with colour-naming in incongruent colour-word pairings (task inhibition) at the interhemispheric level.

V I I . A . P o s t e r 119 RIGHT HEMISPHERE DYSFUNCTION REMITTED SCHIZOPHRENIA

IN

V. Di Michele, I. Conte, F. Bolino, M. Casacchia

University of L'Aquila, Dept. of Psychiatry, L'Aquila, Italy In order to test the hypothesis of a right hemisphere involvement in schizophrenia, sixteen patients with a mild-to-moderate form of illness were assessed, in a controlled study, with a neuropsychological battery including tests sensitive to right hemisphere damage. Two-way Analyses of Variance were performed (with sex and diagnosis as factors), and demonstrated an impairment in conceptual ability for visuo-spatial stimuli (F:I 1.5, p = 0.000), judgement of line orientation (F:4.4, p=0.018) and visuospatial short term memory (F:3.5, p=0.039). No sex effect was detected. However the deficit in short term memory, disappeared when

151 the score of judgement of line orientation was controlled for in an Analysis of Covariance:F(l,38) 2.4, NS, suggesting the existence of a defective visuo-spatial analysis, able to interfere with the mnemonic process of spatial primary memory. This study provides evidence that specific visuo-spatial mental abilities are disrupted in schizophrenia, supporting a growing body of data from neuroanatomy, neuropsychology and Information Processing indicating a right hemisphere dysfunction. In addition our findings encourage to further study the role 0f'the posterior brain and the parietal lobe, in the pathophysiology of schizophrenia. The theoretical model of a lateralized (to the left side) cerebral dysfunction is therefore not supported. Supported by a grant of C.N.R. -PF FATMA- N.93-00615PF41.

V I I . A . P o s t e r 120 DORSOLATERAL PREFRONTAL DYSFUNCTION IN DEPRESSION SCHIZOPHRENIA

CORTEX AND

C.J. Bench, P.F. Liddle, K.J. Friston, C.D. Frith, P.M. Grasby, R.S.J. Frackowiak, R.J. D o l a n

MRC Cyclotron Unit, Hamrnersmith Hospital, London, W12 OHS, UK Positron emission tomography (PET) studies of depression l and schizophrenia 2 have described functional abnormalities in the left dorsolateral prefrontal cortex (DLPFC) in both illnesses. This regional deficit has been associated with the syndromes of psychomotor retardation in depression and psychomotor poverty in schizophrenia. Such findings suggest that the dysfunction in the DLPFC is related not to diagnosis per se but to specific symptoms. This prediction was empirically tested in a retrospective study that pooled data from 40 patients meeting research diagnostic criteria (RDC) for depression and 30 patients meeting DSM-IIIR criteria for schizophrenia. The patients were categorised into those with and without poverty of speech, a symptom that is a nuclear feature and observable manifestation of psychomotor impairment. The profile of regional cerebral blood flow (rCBF), measured in all subjects under resting conditions, was subsequently compared in these two groups using SPM software 3. Patients with poverty of speech had significantly lower rCBF in the left DLPFC. The reduction in rCBF was independent of diagnosis and not explained by dysphoric mood. The findings lend support to the notion of studying symptoms in addition to specific diagnostic groups in the major psychoses. 1.C.J. Bench et al. The Anatomy of Melancholia. Abnormalities of Regional Cerebral Blood Flow in Major Depression. Psychol. Med., 1992; 22: 607. 2. P,F. Liddle et al. Patterns of Cerebral Blood Flow in Schizophrenia. Br. J. Psychiatry, 1992; 160: 179. 3. K.J. Friston and R.S.J. Frackowiak. Imaging Functional

Anatomy. In: Brainwork 2: Alfred Benzon Symposium, Copenhagen. Munksgaard. 1991; 1.

V I I . A . P o s t e r 121 MEDIAL TEMPORAL LOBE PATHOLOGY AND MEMORY IMPAIRMENT IN SCHIZOPHRENIA D.A. N a t h a n i e l - J a m e s , M. Maier, M.A. Ron, R. B r o w n

Institute of Neurology, The National Hospital, Queen Square, London WCIN 3BG, UK Memory studies in schizophrenics have suggested that both verbal and non-verbal memory are impaired and that the severity varies with the method of retrieval; free recall being more affected than recognition, suggesting bilateral temporal lobe pathology. However, recent Magnetic Resonance studies (MRI), suggest that structural abnormalities may be widespread (Harvey et al., 1993), or affect preferentially either temporal lobe (Bogerts et al., 1990). We report a pair of MZ twins concordant for schizophrenia who both showed an unusual dissociation between verbal and non-verbal recognition as demonstrated by performance on neuropsychological tests. The dissociation was between severely impaired facial recognition and preserved verbal recognition. In an attempt to elucidate the nature of this and any other cognitive impairment, further tests of memory, frontal lobe functioning and general intellectual deterioration were administered. No additional impairments were noted. Magnetic resonance spectroscopy of the medial temporal lobe carried out on these twins showed an asymmetry in the N-acetyl-aspartate to creatine ratio more marked in the more severely affected twin. These findings suggest the presence of an abnormality in the right temporal lobe. As only one of the twins was on medication, it is unlikely that this explains the memory disturbance. It is proposed that these abnormalities are likely to be due to genetic or environmental factors acting during fetal life. It is suggested that the pattern of impairment reported here illustrates the heterogeneity in the patterns of cognitive impairment which mirrors that found in structural MRI studies. Harvey I., Ron M.A., Du Boulay G., Wicks D. (1993) Reduction of cortical volume in schizophrenia on Magnetic Resonance Imaging. Psychol. Med. in press. Bogerts B., Ashtari M., DeGreef G., Alvir J.M.S. (1990) Reduced temporal limbic structure volumes on Magnetic Resonance Images in first episode schizophrenia. Psychiatric Res. 35: 1-13.

152 V I I . A . P o s t e r 122

V I I . A . P o s t e r 123

COGNITIVE COMPARED TEMPORAL DISORDERS

FRONTAL MEDIATION OF NEW LEARNING IN HUNTINGTON'S DISEASE AND SCHIZOPHRENIA

DEFICITS IN SCHIZOPHRENIA WITH FRONTAL LOBE, LOBE AND BASAL GANGLIA

S.E. P u r d o n , B.D. Jones, L. Begin, A. Labelle, E. M o h r C. Pantelis a, T.R.E. Barnes b, H.E. Nelson b, B. S a h a k i a n b, T.W. R o b b i n s b

aMental Health Research Institute of Victoria, Private Bag No. 3, Parkville, Vie. 3052, Australia; bCharing Cross & Westminster Medical School, London; Experimental Psychology B'ding, Downing College, Cambridge, UK The frontal lobes, temporal lobes and subcortical structures (eg. basal ganglia and thalami), have been considered important areas in understanding the pathogenesis of schizophrenia. However, few direct comparisons have been made between schizophrenia and neurological disorders affecting these structures. We have previously focused on frontal-subcortical systems in helping to elucidate the nature of the cognitive deficits observed in schizophrenia by relating the pattern of neuropsychological impairments to the symptoms and syndromes of this disorder (Pantelis et al., 1992, BJPsych, 160: 442-460; Nelson et al., 1990, Psychol Med, 20: 357-365). Using the computerised tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which have proved sensitive in discriminating between cortical and subcortical disorders, we have compared chronic schizophrenic patients with matched groups of neurological patients and with normal controls. The computerised version of Shallice's Tower of London Task allows motor and cognitive speeds to be ascertained while subjects solve increasingly complex tasks. In comparison with normal control subjects, matched for age, sex and NART IQ, patients with schizophrenia demonstrated a specific impairment of subsequent thinking time (the time taken to complete a task, subsequent to the first move). This pattern was similar to that found in patients with lesions of the frontal lobe (also matched for age, sex and NART IQ). In contrast, patients with Parkinson's disease demonstrated a specific impairment of initial thinking time ('planning time' - - prior to commencement of the first move). Patients with temporal lobe lesions were not impaired in their performance on this task. Thus, on this task, patients with schizophrenia behave essentially like patients with lesions of the frontal lobe. Patients were also assessed on another CANTAB task, which involves set-shifting (intra- and extra-dimensional shift task). This task is similar to the Wisconsin Card Sort in that it involves unspecified rule changes during performance. Patients with schizophrenia, when compared to the other neurological groups, were found to fail at an earlier stage of this task. The importance to schizophrenia of the frontal lobe, temporal lobe and basal ganglia will be discussed.

Schizophrenia Branch, Institute of Mental Health Research, University of Ottawa~Royal Ottawa Hospital, 1145 Carling Ave, Ottawa, ON, Canada, KIZ 7K4 Executive function deficits in schizophrenia (SC) and Huntington's disease (HD) may implicate similar compromise to the frontal lobes secondary disconnection between subcortical and frontal structures. The present study tested one prediction of a disconnection hypothesis based on the postulate that executive operations influence new learning. It was hypothesized that new learning in both HD and SC could be predicted from executive abilities. Fourteen SC (Age: 47.92+10.04, Education: 10.75___3.19), 14 HD (Age: 50.08_12.59, Education: 13.17___2.66) and 14 normal controls (Age: 63.08+ 12.71, Education: 14.83+2.72) were administered the Wisconsin Card Sorting Test, the California Verbal Learning Test, and the WAIS-R Vocabulary test. For each group, CVLT trial 5 recall was regressed on WCST perseverative errors after entering WAIS-R Vocabulary. Results showed an impressive increase in predicative power for the HD (change in r2=0.23) and SC (change in r 2= 0.24) that was not evident in controls (change in r2=0.01). These data support the contention that schizophrenia and Huntington's disease may share similar compromise of executive operations which in turn supports the disconnection hypothesis.

VII.A. Oral 5 INFORMATION PROCESSING TO REMEDIATE COGNITIVE SCHIZOPHRENIA

STRATEGY DEFICITS IN

P. Stratta, F. Mancini, P. Mattei, M. Casacchia, A. Rossi

University of L'Aquila, S.M. Collemaggio Hospital, Department of Psychiatry, L'Aquila, Italy Several reports have shown encouraging plasticity in some schizophrenic patients' Wisconsin Card Sorting Test (WCST) performance while receiving detailed instructions on the task and reinforcement; however the way of maintaining this improvement and the effect of training on aspects of daily functioning are still unknown (Green, 1993). The identification of a cognitive deficit is the basic step towards its remediation. The lack of an information processing organizational strategy, including the ability to develop a response set and follow a plan of action, has been hypothesized

153 as specific of schizophrenic patients' poor WCST performances (Bellack et al., 1990). To test this hypothesis, WCST was administered to 20 schizophrenic patients with standard instructions and with a modified procedure, forcing the subject to verbally express the criterion of matching before the card sorting. By using the modified procedure, eight (61.5%) of the 13 poor performers dramatically remediated their performances without any task instruction or reinforcement, while remaining five patients did not show any improvement, rather showing an enhanced perseverative pattern. Our findings, albeit preliminary, are intriguing and could be of heuristic value in the distinction of subtypes who probably reflect different pathophysiological characteristics and would potentially benefit from different modalities of treatment and rehabilitation. BeUack A,S. et al., Am J Psychiatry 1990; 147: 1650-1655. Green M.F., Am J Psychiatry 1993; 150: 178-187.

V I I . A . P o s t e r 124 THE ASSESSMENT OF PLANNING ACTIVITY IN SCHIZOPHRENIA USING THE TOWER OF LONDON TASK T. Rushe, P. Woodruff, R. Murray, R. Morris

Department of Psychology and Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AE UK A computerized version of Shallice's Tower of London Task was used to compare planning activity in 26 schizophrenic patients compared with 35 normal matched controls. Patients with schizophrenia took significantly more moves above the minimum required to solve the problems. A motor control condition revealed that movement times were significantly increased in the patient group. Movement times and the number of moves above the minimum number of moves required to solve the problems were found to be correlated with negative symptomatology. Initial thinking (planning) time adjusted for motor slowness, was unimpaired in the patient group, although thinking time subsequent to the first move was significantly prolonged. These findings are comparable to prior studies in which patients with frontal lobe neurosurgery and idiopathic Parkinson's Disease (PD) were tested on similar computerized versions of the task. Patients with schizophrenia are shown to have the same profile of deficits exhibited by the frontal lobe patients in contrast to PD patients, who do not require more moves to solve the problems but have significantly longer planning times. These dissociations need further substantiations, but they are consistent with the view that schizophrenia is characterized by frontal lobe rather than basal ganglia dysfunction.

V I I . A . P o s t e r 125 LANGUAGE, SPREADING ACTIVATION, LATERALITY, AND SCHIZOPHRENIC THOUGHT DISORDER

M. Spitzer, S. Maier, S. Harig, U. Himmelsbach, P. H f r z , O. K o c h

Psychiatrische Universit~itsklinikHeidelberg, Voss-Str. 4, D-69115 Heidelberg, Germany Results from lexical decision tasks support the view that schizophrenic thought disorder (TD) is due to the comparatively faster and further spreading of activation in associative semantic networks. In particular, if indirectly related word pairs (e.g., qemon-sweet') and short inter stimulus interval (ISI) are used, a priming effect can be detected in TD schizophrenic patients compared to non-TD schizophrenic patients and normal controls (Spitzer et al., Biological Psychiatry, in press). In order to further clarify the nature of this phenomenon, a divided visual field study was carried out in with related, indirectly related and non related words as well as with word-non-word pairs were used as stimuli. Compared to normal Subjects (n= 38) and non-TD schizophrenic patients (n = 24), a larger indirect semantic priming effect was found in TD schizophrenic patients (n= 16), which was lateralized to the left visual field (right hemisphere). This result is in line with findings obtained in studies of normal subjects, which are suggestive of right lateralized unfocused activation of lexical items that under ordinary circumstances have little or no contextual relevance. It furthermore specifies the role of the right hemisphere for the formation of schizophrenic thought disorder and can be linked to known lateralized differences of dopaminergic activation.

VII.B. Attention V I I . B . P o s t e r 126 THE EXTENT OF WORKING MEMORY DEMANDS PREDICTS RESPONSE TO NEUROLEPTIC MEDICATION ON CONTINUOUS PERFORMANCE TESTS J.I. Epstein, R.S.E. Keefe, P.D. Harvey, S.E. Lees Roitman, M. Davidson, L.J. Siever, R.C. Mohs

Bronx VAMC, Psych., ll6A, 130 IV. Kingsbridge Rd., Bronx, NY 10468, USA Continuous performance tests have been used for years to measure attentional impairment in schizophrenic patients. Although some data suggest that CPT performance is generally unaffected by neuroleptic medication, there are a number of limitations in those studies, including cross-sectional designs,

154 small sample sizes, and failure to use random assignment to medication conditions. Twenty-five DSM-IIIR schizophrenics were tested both on and off neuroleptics (minimum of 2 weeks in each condition, counterbalanced order) on two versions of the continuous performance test (CPT). One version of the test was a standard 3-7 CPT and the other was an Identical Pairs (IP) version which had a higher working memory load. On the 3-7 CPT there were no differences in errors of omission associated with medication status, while on the IP version there was a significant decrease in these errors associated with medication (unmed = 13.64 + 9.65, med = 9.07 + 7.74, p < 0.03). These data, consistent with results of studies of both primates and humans, suggest that dopaminergic manipulations have a substantial effect on cognitive tests demanding working memory.

VII.B. Oral 6 DIFFERENT PATTERNS OF AUDITORY ATTENTION (PAT) PERFORMANCE DISCRIMINATE BETWEEN HEALTHY SUBJECTS AND CHRONIC SCHIZOPHRENICS R o b e r t Pigache

Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London SE1 9RT, UK Attention is multifaceted and aspects of it are believed to be impaired in schizophrenia. The PAT is a new auditory attention task ~'2 with four subtests (combining diotic or dichotic modes of presentation with slow or fast rates of delivery) as 5 min strings of digits. It imposes no memory load and measures simultaneously: sustained attention, selective attention, and slowness of information processing. The PAT performance of twenty chronic schizophrenics was compared to that of eleven healthy subjects on the first testing of all subjects. The patients were stabilized on various doses of chlorpromazine (CPZ). A new algorithm identified patterns of sustained attention errors over the successive thirds of each subtest. The twenty schizophrenics made significantly more fast, dichotic, and sustained attention errors (especially the latter: schizophrenic 50% v healthy 14%; p<0.02). Thirteen of the patients (NB. when on CPZ) performed as healthy subjects in terms of MIE (i.e. 4 subtests: mean error index). Nonetheless they made more sustained attention errors (35% v 14%; p < 0.05). Sustained attention was predominantly impaired in these patients. 1. Pigache R.M. Schizophrenia Research: 1992, 10, 39-50. 2. Ibid 51-59.

V I I . B . P o s t e r 129 LONGITUDINAL RELATIONSHIPS BETWEEN AUDITORY ATTENTION TASK (PAT) PERFORMANCE AND PSYCHIATRIC RATINGS FOR TWENTY INDIVIDUAL SCHIZOPHRENICS R o b e r t Pigache

Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London SE1 9RT, UK The PAT is an auditory attention task with four subtests (combining diotic or dichotic modes of presentation with slow or fast rates of delivery) as 5 min strings of digits. The task was validated for schizophrenia t and revealed different relapse patterns 2. Also, PAT errors correlated significantly with rating scales scores (BPRS and Global) inter-subject, but were more sensitive to change than either scale and 'predicted' hospital discharge when the ratings did not t. Twenty chronic schizophrenics were tested fortnightly (10 for one year; 10 for two years) and rated concomitantly for one year by independent psychiatrists. All patients were maintained on chlorpromazine (CPZ) with the dose changed (double blind) to include 10 weeks of placebo. The longitudinal data of individual patients showed far greater intra-subject agreement between PAT errors and BPRS or Global scores than indicated by the inter-subject analysis (above), with PAT data more stable and yet more sensitive to placebo. The result further validated the PAT as an objective method for measuring the severity of schizophrenia. 1. Pigache R.M. Schizophrenia Research: 1992, 10, 39-50. 2. Ibid 51-59.

VII.B. Oral 7 COMPONENTS OF VISUAL ATTENTION SCHIZOPHRENIA: NEW FINDINGS

IN

C.S. Carter, L.C. R o b e r t s o n , T.E. N o r d a h l , M. Chaderjian, L. O ' S h o r a - C e l a y a

Dept. of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA 15 unmedicated patients with schizophrenia and 14 normal controls were compared on the global/local task which measures 3 components of attention to complex visual stimuli: (1) attention to stimuli with low or high spatial frequency features, an operation linked to the function of the superior temporal gyrus; (2) strategic allocation of attention to either global or local aspects of a complex stimulus; and (3) the 'attentional print', an automatic carry-over effect which provides a reaction time advantage for stimuli appearing at the same level as that of the preceding stimulus. Patients who had systematized

155 delusions or hallucinations around a theme were deficient in processing low spatial frequency stimuli (local level). This is the pattern of performance seen in patients with left superior temporal gyrus lesions, confirming the association between positive symptoms and left superior temporal gyrus dysfunction. Patients showed a normal ability to strategically allocate attention between levels of the stimulus, consistent with previous studies by our group showing normal control of visual attention in schizophrenia. However patients were deficient on the 'attentional print' effect except when the level of the carry over effect (global or local) was congruent with the level to which attention was strategically directed. This suggests that patients with schizophrenia are deficient in their ability to orchestrate controlled and more automatic components of attention during visual selection.

V I I . B . P o s t e r 130 VISUAL ATTENTION SCHIZOPHRENIA

AND SYMPTOMS

OF

J. A d d i n g t o n , D.E. A d d i n g t o n

University of Calgary, Dept. of Psychiatry, FoothillsHospital, 1403 29th Street, N.W. Calgary, Alberta, T2N 2T9, Canada This study examines the relationship between visual attention and schizophrenic symptoms. Subjects were 40 inpatient admissions who met DSM-III-R criteria for schizophrenia, 40 normal and 40 psychiatric (bipolar disorder in remission) control subjects. In the schizophrenic sample positive and negative symptoms were assessed at hospitalization and again 3 months later during a period of relative remission. Visual attention was measured at both time periods using the Continuous Performance Task (CPT) and the Forced Choice Span of Apprehension Task (SPAN). The normal and psychiatric control subjects were assessed on the CPT and SPAN. Schizophrenics had poorer visual attention than the controls. At followup, for the schizophrenics, poor visual attention was significantly associated with high levels of negative but not positive symptoms, Relative to the significant improvement in symptoms over time the schizophrenics' performance on the CPT and the SPAN improved only slightly. These results have implications for the hypothesis that deficits in visual attention may be negative symptom-linked markers and may have implications for identifying cognitive vulnerability factors to schizophrenia.

V I I . B . P o s t e r 131 NEGATIVE PRIMING EFFECTS IN NORMAL CONTROL SUBJECTS AND SCHIZOPHRENIC PATIENTS M. Spitzer*, P. BShler

Psychiatrische Universitiitsklinik, Voss-Str. 4, 69115 Heidelberg, Germany One mechanism of selective attention is the active inhibition of information which is not relevant for a given task and has to be ignored. In the negative priming paradigm (Tipper SP: The negative priming effect: Inhibitory priming by ignored objects. Q. J. Exp. PsychoL 37A: 571-590, 1985) two different pictures are presented simultaneously in two different colours. One picture (e.g., the green one) has to be recognized while the other (e.g. the red picture) has to be ignored. If the picture to be ignored has to be recognized in a subsequent trial, an inhibitory effect - - negative priming - - on reaction time (RT) can be demonstrated. Data from 5 pilot studies with 35 normal control subjects indicate that this negative priming effect is dependent (1) upon stimuli (pictures produce a larger effect than characters), (2) upon the ISI (negative priming increases with ISI). From what is known about inhibitory processes in schizophrenic patterns, it can be hypothesized that these patients should display a decreased negative priming effect, i.e., a decrease in RTs in negative priming trials.

VII.C. Thought Disorder VII.C. Oral 8 THEORY

OF MIND

IN SCHIZOPHRENIA

R. C o r c o r a n , C.D. F r i t h

Psychology Department, University College London, Gower St., London WC1, UK; MRC Cyclotron Unit, Hammersmith Hospital, DuCane Rd, London W12 OHS, UK The social reasoning and communication difficulties of patients with schizophrenia have been well documented in recent years and have been interpreted in various ways. We propose that a deficiency in a specific cognitive mechanism can explain these difficulties by arguing for an impairment of 'theory of mind'. The term refers to how we infer intentions, beliefs and knowledge states in others. This ability has been extensively studied in children with autism who display severe social and communication problems. Just as previous investigators have stressed the importance of specific symptoms to social difficulties, we expected to find theory of mind difficulties in patients with negative feature schizophrenia and in association with some of the classic positive symptoms. The performance of a sample of patients on several newly

156 developed theory of mind tasks has been compared to that of normal controls and non-psychotic psychiatric patients. Results indicate poorer overall performance by the patients with schizophrenia. Furthermore, there are strong indications that the difficulty is symptom specific.

V I I . C . P o s t e r 133 JUDGMENTS OF CERTAINTY, LOGICAL THINKING AND SCHIZOPHRENIA R, Tevissen a, M. de Bonis b, G. L a n t e r i - L a u r a a

V I I . C . P o s t e r 132 NEUROPSYCHOLOGICAL COGNITIVE CORRELATES CONCEPTUAL THINKING SCHIZOTYPY

AND OF AND

C. L o n e r a g a n ", P.B. W a r d ~, N. M c C o n a g h y ~, S. A n d r e w s b, J. G a s t o n b, P.T. Michie c, B. Clark ~

Schools ofaPsychiatry and bpsychology, University of New South Wales, Prince of Wales Hospital, High St, Randwick, N S W 2013, Australia and CSchool of Behavioural Sciences, Macquarie University, N S W 2109, Australia This study examined neuropsychological and cognitive processes associated with schizotypy in university students. Subjects were screened for alcohol and substance abuse, but were not excluded on the basis of present or past psychiatric history. Several measures of conceptual thinking were obtained, including allusive thinking (McConaghy), measured using the Object Sorting Test, the Thought Disorder Index (Holzman), scored from Rorschach responses, the Thought, Language and Communication Scale (Andreasen), scored from a semistructured free speech sample, and Bizare/Idiosyncratic Thinking (Harrow), scored from the Proverbs test. WAIS Vocabulary and Comprehension subscales were administered as an estimate of verbal IQ. A range of psychometric measures of schizotypy were obtained, including Claridge's STA scale, Raine's Schizotypal Personality Questionnaire, several of the Chapman scales of psychosis-proneness, the Golden-Meehl schizoid taxon items, and the Launay-Slade Hallucination scale. SCID-II items measuring paranoid, schizotypal and schizoid personality disorder were also administered, along with the Symptom Checklist 90 and short forms of the Eysenck Personality Questionnaire. A computerized version of the Wisconsin Card Sorting Test was completed and Eriksen's spotlight of attention and Tipper's negative priming constructs were evaluated using RT tasks. Complete data were obtained from 59 subjects. Preliminary analysis indicated a significant association between high STA scores and increased perseverative errors on the WCST. Negative priming on the Tipper task was not associated with STA score on any other schizotypy measure.

aH3pital Esquirol, 57 boulevard du Markchal Leclerc, 94 219 Saint-Maurice Cedex, France, bCentre National de la Recherche Scientifique, Htpital de Bic~tre, 63 rue Gabriel P~ri, 94 276, Le Kremlin-Bic~tre, France The logic of natural reasoning is highly dependent of the truth value attributed to a verbal statement. In the present study, proverbs (commonsensical beliefs) were used to evaluate truth judgments in schizophrenic patients. Fifteen DSM-III-R schizophrenics, paired for age, sex and verbal IQ to fifteen controls, were asked to rate a sample of thirty-six proverbs (differing with respect to familiarity, complexity and content) on three five-point graphic rating scales: 'true-false', 'agree-disagree' and 'certainty-uncertainty'. Results show that schizophrenics as compared to controls, differ in their ratings. The factorial analysis of the matrix (30 subjects × 5 steps) shows a bias of extremeness for schizophrenics, with a clearcut distinction between patients and controls. The statistical comparison of the two groups on the Peabody composite index of extremeness and direction is significantly higher (U Mann-Whitney= 61 p<0,05) for schizophrenics, as compared to controls. There is a response bias in the direction of certainty in schizophrenics. They overrate the truth value of the proverbs whereas controls use likelihood values. These results suggest a failure in handling the logical modalities of statements about commonsensical knowledge.

VII.C. Oral 9 ARE PATIENT'S WITH THOUGHT DISORDER AWARE OF THEIR DEFICIT?. J.J. M c G r a t h , R. Kerr, F.L. D a r k

Clinical Studies Unit, Wolston Park Hospital, Wacol, Qld. 4067, Australia Syndromes that involve unawareness of deficits provide interesting clues for cognitive neuropsychology. The aims of this study are (I) to systematically examine awareness of communication deficits in groups prone to thought disorder with a new self-report instrument, the Communication Awareness Scale (CAS); (2) to examine associations between CAS scores and performance on tests sensitive to prefrontal systems (WCST, Trail Making, Verbal Fluency and Stroop). Speech samples (scored with the Andreasen's Scale of TLC), the CAS and the neuropsychology tests were collected from three groups (schizophrenia=28, mania= 12 and well controis = 20).

157 The results show that, compared to those without thought disorder, those with positive thought disorder had CAS scores indicative of increased awareness of the needs of the listener (p=0.016), and increased awareness of problems with the maintenance (p = 0.075) and changing (p = 0.064) of set. Overall, increased awareness of deficit was association with prefrontal system impairment. These data suggest; (1) that many thought disordered patients are aware of their communication deficits; (2) that for some thought disordered speakers who are aware of their deficits, the problem may lie in error utilisation rather than error monitoring.

V I I . C . P o s t e r 134 'GESTALT' PROCESSING SYMPTOMS

AND PSYCHOTIC

association test, in which the first word that comes to mind upon a stimulus word is recorded. Bleuler's coworker Carl Jung (Jung CG: Experimentelle Untersuchungen fiber Assoziationen Gesunder, 1906. Gesammelte Werke 2, pp. 24-50, 1979) demonstrated that schizophrenic patients produced more indirect and sound associations and fewer conceptually driven associations than control subjects. More recently, dysfunctional associative processes have been studied by measuring hesitation phenomena in spontaneous speech (Maher et al.: Redundancy, pause distribution and thought disorder in schizophrenia. Language and Speech 26: 191-199, 1983). We tested 9 non-formal thought disordered (NTD), 11 formal thought disordered (TD) schizophrenic patients, and 20 normal control subjects on both paradigms. Results not only corroborate the findings of Bleuler and Jung, as well as of Maher et al. (i.e., TD patients produce shorter pauses before rare words), but also give empirical support to the conceptual link between the two phenomena.

E.R. Peters, A.D. Pickering, D.R. Hemsley

Psychology, Institute of Psychiatry, Denmark Hill, London SE5 8AE UK It has been proposed that a characteristic of schizophrenic processing is an inability to perceive stimuli in a holistic fashion (e.g., Cutting, 1985; Schwartz-Place & Gilmore, 1980). The relationship between 'Gestalt' processing and symptoms of reality distortion in a psychotic population was investigated using a 'degraded interference' task. In this task Stroop stimuli are fragmented, and the extent to which they are visually integrated is inferred by their interfering properties. It was predicted that psychotic individuals would display a chronic pattern of 'bottom-up' processing, and fail to show an interference effect with degraded Stroop stimuli. This predicts faster RTs in the experimental condition, which therefore cannot be attributed to a generalized deficit. The results partially supported the hypothesis: the degraded interference effect, which was highly significant in the control eating disorder group, was reduced and non-significant in the psychotic sample. However, a large variability was observed amongst the psychotic patients, with a reduction in 'top-down' processing being manifest in a sub-sample only. This sub-sample could not be differentiated on any demographic variables, and further work is necessary to obtain a clearer picture of the diversity of function underlying positive symptomatology.

V I I . C . P o s t e r 135 MEASURES OF DISORDERED ASSOCIATIVE PROCESSES IN SCHIZOPHRENIC PATIENTS M. Spitzer*, S. Beyer, S. M a i e r

Psychiatrische Universitiitsklinik, Voss-Str. 4, 69115 Heidelberg, Germany Bleuler conceived schizophrenia as a disorder associative process. At his time, this was studied by means of the word

VII.D. Memory V I I . D . P o s t e r 136 SEMANTIC MEMORY SCHIZOPHRENIA

IN ACUTE

S.D.E. Rudge, A.M. M o r t i m e r , B.J. Corridan, K. Kho, F. Kelly, M. Bristow, M. T h u r s t o n , P. Taylor

Charing Cross & Westminster Medical School c/o West London Healthcare NHS Trust, Uxbridge Rd., Southall, Middlesex UB1 3EU, UK 45 DSM-III acute schizophrenic, cognitively intact patients were assessed for semantic memory dysfunction using the Hodges battery. Independent ratings of delusions, bizarre/fragmentariness of delusions and thought disorder were made using the C.A.S.H. Mahalanobis distance analysis did not reveal groups of patients with similar impairments. However, the proposed hierarchical structure of semantic memory was supported statistically across tests using clustering, h-plot and metric scaling techniques: no category specific deficits were found in the group or in individuals. Errors aggregated by type, intrusive versus perseverative, across tests. Perseverative errors were linked with total produced on fluency and definitions, but this was not the case for intrusions. Clustering and graphical modelling procedures suggested that intrusive errors were strongly linked to thought disorder, while delusions and bizarreness/fragmentariness were linked, less strongly, to perseverative errors. Asking for a definition may be a useful clinical procedure in the assessment of thought disorder. Perseveration, implying inability to shift attention or alternatively a memory deficit, may have a bearing on delusions but the relevance of this relationship is unclear.

158

VII.D. Oral 10 W O R K I N G M E M O R Y D E F I C I T S IN S C H I Z O P H R E N I C S W I T H SEVERE SELFCARE DYSFUNCTION R.S.E. Keefe, C. Blum, P.D. Harvey, M. Davidson, S.E. Roitman, K.L. Davis

Psychiatry Service ( l l6A ) , VAMC, Mount Sinai School of Medicine, 130 West Kingsbridge Road, Bronx, N Y 10468, USA Schizophrenic patients who require life-long hospitalization or institution-like care are the most in need of study. Previous studies suggest that schizophrenics with the 'kraepelinian' syndrome of severe dysfunctions in self-care, who demonstrate complete dependence on others for basic necessities for at least the past 5 years, differ from other chronic schizophrenics in that they demonstrate greater left/right asymmetry of the anterior ventricles, more severe negative symptoms and formal thought disorder, and a greater family history of schizophrenia spectrum disorders. This study assessed cognitive functions in 16 kraepelinian and 18 nonkraepelinian schizophrenics matched for age, education, and duration of illness. Groups performed similarly on tests of general verbal and nonverbal intelligence, verbal memory, and executive function (all p's>0.10). Kraepelinian schizophrenics performed significantly worse on a test of visuospatial working memory, which in nonhuman primates is mediated by neurons in the dorsolateral prefrontal cortex (t= 2.48, df=32, p<0.01). Kraepelinian patients also performed significantly worse on a test of visuospatial span, and had a greater Trails B/A ratio, a measure of frontal lobe function. These data suggest that working memory deficits are associated with severe self-care dysfunctions in schizophrenia, and are consistent with previous findings of anterior ventricular abnormalities in these patients.

VII.D. Poster 137 I N F L U E N C E OF M E D I C A T I O N STATUS AND DISEASE SEVERITY ON IMMEDIATE AND RECENT MEMORY PERFORMANCE IN C H R O N I C S C H I Z O P H R E N I A G.P. Lee, S.L. Haverstock, B.I. D i a m o n d , R.L. Borison

Departments of Psychiatry & Health Behavior and Surgery, Medical College of Georgia, Augusta, GA, 30912, USA Studies reporting hippocampal morphological abnormalities in schizophrenics have renewed interest in the memory functioning of these patients. However, investigations of memory in schizophrenia have yielded contradictory results. This may be due, in part, to the confounding factors of medication status and disease severity. To determine the influence of these factors on various forms of memory, we examined the performance of chronic schizophrenics on measures of immediate memory

(Digit Span), recent memory (Digit Supraspan and Recurring Figures), and psychosis severity (Brief Psychiatric Rating Scale) off and on antipsychotic medication. There were statistically significant improvements in psychosis severity and immediate memory among individuals treated with haloperidol. However, there were no differences in verbal or visuospatial recent memory in schizophrenics treated or untreated with haloperidol. Results suggest: (1) Immediate memory (attention span) improves as the psychosis is controlled pharmacologically, (2) there is no recent memory deficit in schizophrenia, and (3) recent memory performance is not significantly influenced by moderate doses of haloperidol or by mild psychosis in a chronic schizophrenic population. Although there may be hippocampal abnormalities in some schizophrenics, these may not be sufficient to create significant memory impairments.

VII.E. Familial Aspects VII.E. Poster 138 NEUROPSYCHOLOGICAL

ABNORMALITIES IN THE RELATIVES OF FAMILIAL S C H I Z O P H R E N I C S P.B.L. Birkett, T. Sigmunsson, T. Sharma, T.D. Griffiths, S. F r a n g o u , R.M. Murray, A . M . Reveley We examined 27 first and second degree relatives of schizophrenics (SR) from families containing at least two affected individuals. They were compared with 30 normal controls (NC) on a variety of neuropsychological measures including verbal fluency tasks and a computerised version of the Stroop task. The schizophrenics' relatives showed significantly slower reaction times in naming a colour with a neutral distractor (Mann-Whitney 2-tailed p = 0.0057), a Stroop colour-word (p = 0.0113) and a negatively primed colour-word (p = 0.0283). There were no significant differences in rank order between the groups for the Stroop effect or negative priming effect, although the SR group showed a larger spread. Differences on the verbal fluency tasks were more apparent on a spelling-based test (words beginning with 'S') than on a semantic task (four-legged animals), and were most striking within the first 15 s of a 60 s task (S-Words in 15 s" NC Mean 7.9 SD 2.2; SR 5.2 SD 1.8; p < 0.0001). Performance differences between 30 and 60 s were not significant in either task. We hypothesise that some schizophrenics' relatives may show impairment in the generation of rapid verbal responses which may be partly masked by other cognitive processes.

159

VII.E. Poster 139 NEUROPSYCHOLOGICAL FUNCTIONING OF S C H I Z O P H R E N I C S AND T H E I R ILL A N D WELL FAMILY MEMBERS G. Lee, L.E. DeLisi

Department of Psychiatry, Health Science Center T-IO, SUNY Stony Brook, Stony Brook, N Y 11794, USA Previous studies have shown that schizophrenic patients typically exhibit some evidence of neuropsychological impairment (Hoff et al., 1992). Though it has been argued that a genetic component may be responsible for differences in the neuropsychological functions of schizophrenics, it is unclear whether such a genetic component alone is sut~cient to bring about these differences. To investigate possible familial influences on neuropsychological functioning, we assessed ill and well siblings and parents of 19 schizophrenics through a neuropsychological test battery which was constructed to measure several neuropsychological functions that have been shown to be typically impaired in schizophrenics. A preliminary analysis of our data suggests that differences of performance on this battery are more significant between schizophrenics and their well siblings and parents than are differences between schizophrenics and their ill siblings. Further, after controlling for age and educational level, differences of performance scores between schizophrenics from different families do not appear to be significantly greater than those between schizophrenics within the same family. Though this initial finding may suggest that familial influences do not play a significant role in the neuropsychological functioning of schizophrenics, more detailed analyses are needed to rule out the possibility of a familial effect that may either precipitate or engender neuropsychological impairment. Such analyses are in progress and will be presented. Hoff, A.L., Riordan, H., O'Donnell, D.W., and DeLisi, L.E. (1992) Cross-sectional and longitudinal neuropsychological test findings in first episode schizophrenic patients. Schizophr. Res. 5, 197-198.

VII.E. Oral 11 P300 IN FAMILIAL A N D N O N F A M I L I A L SCHIZOPHRENIA S. F r a n g o u , G. Alarcon, T. Sharma, N. Takei, C. Binnie, R.M. M u r r a y

Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF,, UK Auditory P300 responses have previously been reported to have decreased amplitude and prolonged latency in schizophrenic patients. Similar abnormalities were reported in patients

with schizotypal or borderline personality disorder and in first degree relatives of schizophrenics. These abnormalities appear to be independent of medication and of psychopathology at the time of testing. P300 is also linked to cognitive processes that appear to underline the genesis of the psychotic symptoms. Because of these associations P300 has been proposed as a genetic trait marker for schizophrenia. The present study was designed to investigate whether the P300 can help define the endophenotypic status of nonschizophrenic family members in familial and nonfamilial schizophrenia. We tested 12 multiply affected families with at least two affected members. Auditory P300 responses during the standard two-tone discrimination paradigm were recorded from 22 medicated schizophrenics, 51 nonschizophrenic first degree relatives and 21 normal controls. There was a significant increase in P300 latency (p = 0.003) and a significant decrease in P300 amplitude (p=0.001) in the schizophrenic group compared to normals. Similarly P300 latency was increased (p=0.012) and P300 amplitude was decreased (p= 0.021) in their first degree relatives compared to controls. The difference between the schizophrenics and their relatives was not significant. The frequency distribution of the amplitude and latency of the P300 suggested a bimodal distribution in the group of relatives. Mixture Density Analysis will be applied to determine the two populations. Results from our sample of nonfamilial schizophrenics and their first degree relatives will also be reported.

VII.F. Social Behavior VII.F. Oral 12 SOCIAL COMMUNICATION SCHIZOPHRENIA

IN

J.F. Whittaker, J. Connell, J.F.W. D e a k i n

Univ. Dept. Psychiatry, Rawnsley Bldg, MRI, Oxford Rd, Manchester M13 9WL, UK Post-mortem brain studies at Manchester University reveal consistent abnormalities in the basolateral circuit. This comprises orbital frontal cortex and anterior temporal lobe. The basolateral circuit appears to be critical for effective integration of social information. The channels of social communication include language (content and prosody), facial expression and gesture. Many of the symptoms of schizophrenia can be understood as disturbances in the reception and expression of social information [1]. To seek functional correlates of the basolateral abnormalities, we sought to relate abnormalities of expressive social behaviour to impaired frontal lobe function, and abnormalities of perception of social cues to impaired temporal lobe function. Schizophrenic patients were impaired in identifying the affect displayed in photographs of faces. Ability to make facial movements and to stress a word when reading a sentence aloud were unimpaired. However, the ability to generate facial expressions of emotion and to read sentences to convey an emotion,

160 were significantly impaired in the schizophrenics. Impairments on these two tasks were correlated (r=0.5, p<0.05). Schizophrenics appeared to have specific impairments in the ability to understand and express emotion. These deficits may be directly related to the formation of paranoid delusions in patients and to the induction of high levels of expressed emotion in relatives. Emotional expression ratings +__SD

Controls (n = 11) Schizophrenics (n = 16)

Facial

Speech

17.0 ___1.9 11.7 + 3.7

28.8 + 2.3 23.8 ___5.0

VII.G. Comparisons to Epilepsy V I I . G . O r a l 14 VERBAL LEARNING DEFICITS IN FIRSTEPISODE SCHIZOPHRENIA: COMPARISONS AND CONTRASTS TO TEMPORAL LOBE EPILEPSY W.B. Barr, R.M. Bilder, A.I. T r r s t e r , N. Schaul, J.L. Lieberman Research Department, Hillside Hospital, Long Island Jewish Medical Center, P.O. Box 38 Glen Oaks, New York, 11004, USA

1. Deakin et al (1992) Clin. Neuropharm., 15(1A), 495-497.

V I I . F . O r a l 13 NEUROPSYCHOLOGICAL DEFICITS MAY BE THE PRIMARY DETERMINANT OF FUNCTIONAL DISABILITY IN SYMPTOMATICALLY STABLE PATIENTS J. Jaeger, S. Berns, A. Tigner, E. Douglas Hillside Hospital, 75-59 263rd St., Glen Oaks, N Y 11004, USA Residual psychopathology is a poor predictor of impaired instrumental role functioning in stable patients. The nature and prevalence of neuropsychological (NP) deficits among patients with schizophrenia make them a reasonable culprit for producing this disability. We report findings of two studies. The first was a preliminary outcome followup study in 34 consecutive patients (50% with schizophrenia, the remainder affective disorders) discharged from a psychiatric rehabilitation program. Results of a step-wise multiple regression revealed that residual executive dysfunction at time of discharge (Wisconsin Card Sorting Test perseverative error score) is strongly predictive of failed instrumental role functioning three months following discharge after covarying for Verbal IQ at discharge and psychopathology at followup (BPRS total score) (p<0.002). As there were no diagnostic differences in the predictive value of NP deficits, we examined data from a second independent study in which we performed a comprehensive neuropsychological battery on functionally disabled patients consecutively admitted to an intensive rehabilitation service. Findings revealed that patients with affective disorder (n=23) and those with schizophrenia (n=32) were equally impaired across all cognitive domains. Thus, neurocognitive deficits may represent a significant barrier to independent occupational functioning among the psychiatric patients regardless of DSM III-R diagnosis.

Temporal lobe epilepsy (TLE) is often used as a model for understanding the biological basis of schizophrenia. The purpose of this study was to examine neuropsychological evidence of left mesiotemporal dysfunction in schizophrenia through comparisons and contrasts to patients with chronic temporal lobe epilepsy. We studied verbal learning performance (California Verbal Learning Test; CVLT) in 45 patients with first-episode schizophrenia (FES), 60 patients with temporal lobe epilepsy (TLE; 31 left, 29 right), and 33 normal-controls. Significant group differences were observed in all CVLT scores except error indices. Post-hoc comparisons revealed similarities between the FES and left TLE groups with both groups exhibiting lower scores on initial learning measures than right TLE and normalcontrol groups. Differences between the schizophrenia and left TLE groups were limited to a more conservative response-bias in the FES group. The results show striking similarities between the learning characteristics of patients with FES and those with left TLE. These similarities are supported further by the contrasts to patients with right TLE. The findings are consistent with results of recent studies showing left temporolimbic abnormalities in schizophrenia and suggest that verbal learning deficits in schizophrenia and left TLE may be mediated by similar neuropathological mechanisms.

V I I . G . P o s t e r 141 LATENT INHIBITION EPILEPSY

IN TEMPORAL

LOBE

N.S. G r a y , N. M o r t o n , J. Mellers, B. Toone, W.A. L i s h m a n , J.A. G r a y Institute of Psychiatry, De Crespigny Park, London SE5 8RQ, UK Latent inhibition (LI) is an attentional task which consists of a retardation of learning the significance of a conditioned stimulus (CS) if it has previously been preexposed without consequence. LI is abolished in acute schizophrenics and is disrupted by amphetamine, a drug known to give rise to

161 psychotic symptoms. Disruption of LI is also produced by lesions to the limbic system in animals. Temporal lobe epilepsy is primarily characterised by mesial temporal pathology and is associated with an increased prevalence of schizophreniform psychosis. Temporal lobe epilepsy provides a useful group, therefore, with which to study both the neuroanatomical basis of LI and its relationship to psychotic symptomatology. Two groups of temporal lobe epileptics were studied: (1) patients with a recorded diagnosis of psychosis other than affective psychosis; and (2) an epileptic non-psychotic sample matched for age, sex, and frequency of seizures. The data presented represent preliminary findings. Against predictions, there was a trend for LI to be reduced in the non-psychotic group as compared to the psychotic group [F(1,11)=3.34, p<0.09], indicating the primary importance of neuropathology in the mediation of LI.

VII.H. Miscellaneous VII.H. Poster 141A SENSORIMOTOR GATING AND HABITUATION IN SCHIZOPHRENIA F. Bolino, V. Di Michele, L. Di Cicco, E. Daneluzzo, V. M a n n a , I. Conte, M. Casacehia

University of L'Aquila, Dept. of Psychiatry, L'Aquila, Italy Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. In the present study the Startle Reflex paradigm evoked by electrocutaneous stimulation was investigated in order to assess gating and habituation phenomena in schizophrenia. In the first experiment 18 schizophrenics and 20 controls were studied. Data revealed the existence of gating effect: MANCOVA: F(4,144)= 22.25, p=0.000, in both groups without any group differences: F(1,35)=0.11, NS. In the second experiment 19 patients and 22 controls were studied. Significant group differences emerged: ANCOVA: F(1,38)=3.54, p=0.06 with the persistence of a habituation effect F(3,117)= 34.33, p = 0.000. However, schizophrenics showed a weaker pattern of habituation, as suggested by the group X trial interaction: F(3,117) = 5.26, p = 0.002. These data suggest that specific abnormal deficits in information processing are present in schizophrenia. Habituation deficit is the most relevant abnormality. Our findings are consistent with the hypothesis of an impairment of a systemic supramodal central mechanism of information processing and support the theoretical model (Bogerts, 1992) which involves a dysfunctional hyppocampus/amigdala activity in schizophrenia. Supported in part by a grant of the National Research Council Targeted Project, FATMA, Subproject SP-4, N. 93-00615-PF41.

V I I . H . P o s t e r 142 DEFICITS IN ORIENTATION ARE PRIMARY SYMPTOMS OF DEMENTIA IN GERIATRIC SCHIZOPHRENIC PATIENTS P.D. Harvey, M. C o t h r a n , L. White, P. Powchik, M. D a v i d s o n

Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY 10029, USA Many geriatric schizophrenic patients manifest a severe form of cognitive impairment resembling dementia. Several characteristics of this impairment are distinct from that seen in dementing conditions such as Alzheimer's disease, including relatively less severe impairments in retention memory. This study examined the specific cognitive impairments that discriminated geriatric schizophrenic inpatients (n = 334) who varied in the severity of global cognitive impairment. Performance on individual items of the Mini-mental State Examination was used in regression analyses to predict the severity of overall cognitive impairment indexed by structured rating scales. The best discriminators of unimpaired from mildly impaired patients were aspects of temporal orientation (i.e., knowing the season and year), while writing a sentence and orientation to place best discriminated mild and moderate dementias. Moderately demented cases were discriminated from severely demented cases on the basis of ability to follow commands and repeat language. Thus, in contrast to Alzheimer's disease where memory impairments characterize even mild cases, deficits in orientation seem to be the best indicator of the presence of a mild dementia in geriatric schizophrenic patients, with more severe cases marked by deficits in behavioral organization. These data indicate that specific aspects of orientation may be core signs of dementia in schizophrenia and suggest that efforts to find neuropathological causes of dementia focus on this aspect of functioning.

V I I . H . P o s t e r 143 OLFACTORY IDENTIFICATION PRE- AND POST-MENOPAUSAL WITH SCHIZOPHRENIA

ABILITY WOMEN

IN

K.P. G o o d , L.C. Kopala, W . G . H o n e r

Department of Psychiatry, University of British Columbia 2775 Heather Street, Vancouver, BC, Canada, V5Z 1M9 Olfactory identification deficits were reported in male patients with schizophrenia. We now report on the examination of olfactory function in 15 pre-menopausal (age 33.7 years), and 12 post-menopausal women with schizophrenia (age 54.3 years) and a control group of 17 pre-menopausal (age 36.8 years) and 12 post-menopausal women (age 55.6 years). We wished to examine whether olfactory deficits would become apparent

162 after estrogen depletion. Olfactory testing was performed and estradiol levels were taken on two occasions. For the premenopausal women, testing was completed on day 1 of the menstrual cycle and again at day 14. Olfactory identification deficits were observed in post menopausal women with schizophrenia (~=26.5). These women scored in the microsmic range (as defined by standardization data), and scored significantly lower than the premenopausal women with schizophrenia (5c= 31.5) and both normal control groups (pre ~ = 37.6; post ~ = 36.8)(F(3,47) = 20.8, p < 0.0001). As well, the pre-menopausal women with schizophrenia scored lower on the olfactory test than the normal control groups. Pre-menopausal women with schizophrenia had lower estradiol levels at day 14 but similar levels at day 1 compared to controls. The post-menopausal women with schizophrenia also had lower estradiol levels than the normal age equivalent group. Thus, olfactory identification deficits in schizophrenia may be accentuated by estrogen depletion.

V I I . H . P o s t e r 144 SACCADIC INTRUSION IN SMOOTH PURSUIT EYE MOVEMENTS (SPEM) OF SCHIZOPHRENIC PATIENTS K.-M. Flechtner, A. Mackert, S. Traversi

Psychiatrische Klinik der Freien Universitdt Berlin, Eschenallee 3, 14050 Berlin, Germany SPEM dysfunctions are considered to be a promising biological marker for schizophrenia. Mostly qualitative ratings such as visual inspection or quantitative measures such as gain (ratio stimulus velocity to eye velocity) have been used to assess quality of SPEM performance. Newer recording techniques like the infrared scleral reflection allow a more detailed quantitative assessment of saccadic intrusions. We examined SPEM performance of 30 schizophrenic inpatients after a drug-free period of several days and compared them with SPEM of 30 healthy volunteers. Psychopathology, especially severity of negative symptoms, number of previous manifestations of the illness and previous neuroleptic medication were documented. Subjects were asked to follow with their eyes a red laser light point moving sinusoidally with a frequency of 0.4 Hz. Eye movements were recorded with the infrared scleral reflection technique. In order to assess quality of SPEM we counted the number of saccades and classified them according to catch-up saccades, anticipatory saccades and square wave jerks. Schizophrenics showed significantly more saccadic intrusions than healthy volunteers. First results indicate that saccadic intrusions in schizophrenics consist primarily of catch-up saccades. There were no significant correlations to psychopathology or previous doses of neuroleptic medication. Our results indicate that saccadic intrusions in schizophrenics are not caused by dysinhibition of the saccadic system but rather suggest a functional impairment of the smooth pursuit system.

V I I . H . P o s t e r 145 HALOPERIDOL INCREASES LATENT INHIBITION IN HIGH SCHIZOTYPAL SUBJECTS

J.H. Williams a*, N.A. Wellman a*, J.N.P. Rawlins b, D.P. G e a n e y c, P.J. C o w e n c, J. F e l d o n b

Departments ofaPharmacology, bExperimental Psychology and CPsychiatry, Oxford, OX3 1UD, UK Latent Inhibition (LI) is the delay of associative conditioning if the conditioned stimulus (CS) has been pre-exposed without reinforcement. Schizophrenics and high schizotypal healthy subjects show reduced LI: pre-exposed schizophrenic or high schizotypal subjects show faster conditioning than pre-exposed controls. We studied the effects of Haloperidol and schizotypy on LI. 95 healthy subjects completed a schizotypy scale. They then received Haloperidol (0.5 mg i.v.) or saline (double-blind) and performed a computerised Stroop colour-naming task. Finally, they attempted an associative conditioning task using as the CS either a pre-exposed colour word (from the Stroop paradigm) or a non-pre-exposed colour word. We analyzed median learning speeds using a 2 x 2 x 2 design of pre-exposure x Haloperidol x schizotypy. There was clear LI overall: subjects showed slower conditioning of the pre-exposed colour word than of the novel colour word (/7<0.005). Haloperidol enhanced this effect (preexposure x drug: p<0.025). Furthermore, this enhancement was most apparent in high schizotypal subjects (3-way interaction: p < 0.025). These results indicate that specific psychological effects of dopamine blockade are detectable in healthy high schizotypal subjects. LI provides a potential psychological model for investigating anti-psychotic drug action in man. Funded by Bristol-Myers-Squibb.

V I I . H . O r a l 16 COGNITIVE IMPAIRMENT IN ELDERLY SCHIZOPHRENIC PATIENTS M. Davidson*, V. H a r o u t u n i a n , S.M. Gabriel, P. Powchik, P.D. Harvey, R.C. M o h s , K.L. Davis

Department of Psychiatry ( l16A ), Bronx Veterans Affairs Medical Center, Bronx, N Y 10468, USA In an effort to define the cognitive impairment often seen in elderly schizophrenic patients, we compared their patterns of cognitive impairment to that in Alzheimer's disease (AD) patients matched to one another and to normal controls on the basis of gender, age, and education. The schizophrenic and the AD patients were also matched by level of severity of

163 global dementia. Geriatric schizophrenic patients performed better than the AD patients on delayed recall but worse on object naming and praxis across all levels of global dementia severity. Confirming the notion that the cognitive impairment in schizophrenia is associated with different neural mechanisms was the lack of plaques, tangles, cholinergic deficiency, or Alz50 reactivity in comparison to brain tissue derived from patients with a clinical diagnosis of AD. Although both disorders present abnormal peptide concentrations, the distribution of peptidergic abnormality across brain regions was distinctly different. Neuropeptide Y concentrations and to a lesser extent CCK and VIP were reduced in schizophrenic patients, somatostatin (SLI) in both schizophrenic and AD patients, while CRF concentrations were reduced only in the cortex of AD patients. The neuropeptide deficits in the schizophrenic patients were more pronounced in the temporal and frontal lobe areas than in parietal and occipital lobe tissues. Likewise, synaptophysin immunoreactivity (EP-10) was found abnormal in both elderly schizophrenics and AD patients, with frontal and temporal lobe deficits in AD, and temporal lobe deficits in schizophrenics. That consistent neuropeptide and synaptic protein deficits reside in the temporal lobe of the schizophrenics implicates the involvement of this region in schizophrenia. The reduction of NPY and SLI in schizophrenia is consistent with the speculation that NPY and SLI colocalizing cortical neurons are especially susceptible to degeneration in elderly schizophrenics.

V I I . H . P o s t e r 146 NEUROPSYCHOLOGY SCHIZOPHRENIA

OF ELDERLY

S.J. Cox, A.M. M o r t i m e r

Charing Cross & Westminster Medical School, c/o West London Healthcare, NHS Trust, Uxbridge Rd., Southall, Middlesex UB1 3EU, UK 40 elderly schizophrenic inpatients were assessed as part of a prospective post-mortem study. Less than 1/4 were able to complete full neuropsychological testing owing to apparent dementia or in some cases negativism. As a whole the sample was moderately demented with even those able to complete the protocol having measurably reduced IQ. Patients able to be tested demonstrated deficits in memory and executive function which were disproportionate to the general decline in cognitive function. They also had a different pattern of schizophrenic syndromes when compared with the more demented patients. One interpretation of the relationship between specific and general cognitive deficit in elderly schizophrenics is that patients develop specific memory and frontal dysfunction as a prodrome to the onset of general cognitive decline, which would suggest a degenerative process. The relevance of neuropsychological deficits to syndrome patterns was explored: psychomotor poverty was associated with general impairment, and reality distortion with frontal and memory dysfunction. Disorganisation

syndrome was not differentially related to type of neuropsychological impairment.

V I I . H . P o s t e r 147 AN EVALUATION NEUROCOGNITIVE SCHIZOPHRENIA

OF COMPUTERIZED ASSESSMENT OF

R.H. Heslegrave, L.N.P. Voruganti, A.G. Awad

Dept. of Psychiatry, Wellesley Hospital, 160 Wellesley St. E., Toronto, Ont., M4Y J3, Canada The current investigation evaluates a new PC-based computerized neurocognitive assessment package developed at the University of Nebraska that incorporates traditional neuropsychological tests, such as the Wisconsin card-sort test, with more experimental tests, such as the embedded sets procedure to study redundancy-associated deficits and the effects of preparatory intervals on reaction time. These tests, along with the Mueller-Lyer visual illusion, a size estimation task, a visual backward masking (iconic memory) test with differing stimulus onset asynchronies, and a span of apprehension test, make up the battery that takes about 25-30 minutes to administer. To date we have successfully applied this test battery to medicated patients in an acute phase following admission as well as to patients later in their short-term hospitalization. This test battery appears to be sensitive to many of the deficits previously associated with schizophrenia and has practical advantages over other approaches to neuropsychological assessment including its ease of application, short administration time, and limited necessity for professional and support staff resources. Data from this test battery has also revealed some interesting new information. In the examination of varying (or irregular) preparatory intervals (from 1-9 s) before an imperative stimulus, schizophrenic patients showed markedly reduced reaction times across all preparatory intervals. However, while normal control subjects improve their reaction times as preparatory intervals lengthened from I-3 s (with performance stabilizing at 3 s), schizophrenic patients show growing impairment in performance over 1-3 s of preparation; their performance does not stabilize until a preparatory interval of 6 s precedes the imperative stimulus. Perhaps of more interest is the effect that occurs when specific preparatory intervals (3, 5, and 8 s) for the warning stimulus are randomly accompanied by visual distractors. In normal subjects, visual distraction during a short (3 s) preparatory interval results in an impairment in reaction time performance but such distraction has little effect at longer preparatory intervals. However, for schizophrenic patients, visual distraction during a 3-s preparatory interval led to a marked improvement in performance, no effect during a 5-s interval, and impaired performance at 8 s. Thus, the beneficial or detrimental information processing effect of competing stimuli in schizophrenic patients appears to be temporally dependent.

164 V I I . H . O r a l 17 HEMISPHERE RELATED NEUROPSYCHOLOGICAL ACHIEVEMENT AS A RISK FACTOR FOR SCHIZOPHRENIA W. Maier, P. Franke, M. G~insicke, F. Rist

Department of Psychiatry, Universityof Mainz, Mainz, Germany It is widely held that schizophrenia is preferentially related to left hemisphere pathology. If this relationship has an etiological meaning, left hemisphere dysfunction should occur among subjects at elevated risk to schizophrenia. Modality specific neuropsychological achievement can reflect hemisphere specific deficits (preferentially in memory and attention tasks). The involvement of the hemisphere related achievement in the pathogenesis of schizophrenia can be considered by two different strategies: (I) by comparing healthy relatives of schizophrenics before passing the age at risk (as subjects at elevated risk for schizophrenia) to healthy controls; (2) by exploring the covariation between schizophrenia related personality traits (social or physical anhedonia, schizoidia, perceptual aberrations) and hemisphere related achievement. As neuropsychological indicators we used the recurrent memory span task (reflecting the consolidation process localized in the hippocampal region) and recognition tasks (with stimuli presented in a visual field specific manner). Schizophrenics (n = 40) were deviant from controls by showing left hemisphere deficits in all mentioned tests. Relatives of schizophrenics (n=40) demonstrated similar deviations in recurrent memory span test with words but not with blocks as stimuli (without overall differences in memory performance) pointing to a left hemisphere deficit in subjects at risk for schizophrenia.