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associated with duration of initially untreated psychosis. These findingssuggest that early neurodevelopmental disturbance(s) in schizophrenia arefollowed by an active, morbid process that is reflected in the expressionof psychosis.

Supported by the Health Research Board.

I8-56-41 Neural Cell Adhesion Molecules andtheDevelopmental Hypothesis of Schizophrenia

L.K. Srivastava, D. Barbeau, 1.1.Liang, G. Flores, R. Quirion. DouglasHospital ResearchCentre, Departmentof Psychiatry, McGill University,Montreal, Quebec, Canada

The neural cell adhesion molecule (NCAM), is a cell surface glycopro­tein involved in many neurodevelopmental processes. One of the manyvariants of the molecule, the highly polysialylated NCAM (PSA-NCAM)is present on neuronal and non-neuronal cells in the embryonic andearly developmental stages and facilitates neuronal migration, axonaloutgrowth and synaptogenesis. In adult brain, its expression is confinedto regions such as the olfactory bulbs, hippocampus, and hypothalamusthat undergo continued synaptic rearrangement. In adults, PSA-NCAMlevels have been reported to correlate with learning, memory and reac­tive synaptogenesis. We have examined the expression of NCAM andPSA-NCAM in the hippocampus of post mortem schizophrenic (n '"10) and control (n '" I 1) brains. Immunohistochemical staining of thehippocampal formation in controls using a monoclonal antibody againstthe PSA portion of NCAM revealed a moderate to high level of irn­munosraining in the dentate gyrus and hilus regions. A majority of theschizophrenic hippocampi (8 out of 10) showed a marked reduction in thenumber of hilar cells positive for PSA·NCAM immunoreactivity. Sincethere is no significant change in total NCAM levels, these results suggestmodifications of post-translational processing (sialylation) of NCAM inschizophrenic brains. In order to study mechanisms of polysialylationof NCAM in animal models, we have cloned the gene for a rat 01-2,8polysialyltransferase (PST), an enzyme essential in adding polysialicacid chains on NCAM. The rat gene, which is highly homologous tothe human gene, is expressed in a developmentally regulated mannerin rat brain with highest levels observed in the embryonic brain. Insitu hybridization of PST mRNA shows prominent expression of thetranscript in the hippocampus and frontal cortex. The cloning of PSTprovides a molecular probe to investigate possible alterations of NCAMpolysialylation in schizophrenia.

I8-56-51 Neuroimaging in Schizophrenia: From Acute toChronic Illness

Antonio Vita. InstituteofPsychiatry, University ofMilan, Milan, Italy

Several structural brain abnormalities have been demonstrated in schizo­phrenia, but the developmental vs. acquired and progressive nature ofsuch abnormalities is still matter of debate.

We have address the issue with different, independent lines of researchfocusing both on acute and chronic schizophrenia:

I. Ventricular size, detected in patients with first episode acuteschizophreniform disorder, then remitted for variable amounts of time,did not change over a period 2 to 10 years when patients were re-scannedafter developing schizophrenia;

2. Distribution of ventricular size in a large schizophrenic sample didnot significantly differ from normality even after correction for age, sexand type of scanner utilized;

3. Age-effect on ventricular size is not substantially different in schi­zophrenics and normals, so excluding an anticipated effect of aging oncerebral structures of schizophrenics.

All these findings support the hypothesis of the neurodevelopmentalnature of brain abnormalities in schizophrenia.

P Poster Presentations

~ Poster Presentations

IP-15-1 I Long-Term Safety of Risperidone

Martin Brecher. JanssenResearchFoundation, Titusville, NJ, USA

Studies have been conducted to assess the safety and efficacy of risperi­done administered to patients with chronic schizophrenia over a period ofup to I year. Safety data from three studies are available: (I) a double­blind study of 99 patients who received a mean of 9 mg/day of risperidoneover a mean period of 227 days; (2) an open label study of 265 patientswho received a mean of 8.5 mglday of risperidone for a mean of 184days; and (3) an open-label study of 107 patients who received a meanof 8.3 mg/day of risperidone for a mean of 206 days. One patient died(suicide) during treatment with risperidone. No unusual serious adverseevents occurred, and, with the exception of myocardial infarction andconvulsions, no serious adverse event unrelated to the underlying illnessoccurred in more than one patient. The two cases of myocardial infarctionwere reported in men aged 60+ who had risk factors for myocardialinfarction. Convulsions associated with hyponatremia were reported intwo patients and convulsions associated with head trauma in one. Thepattern of adverse events observed in the long-term studies was similar tothat observed in the three large double-blind short-term studies. Severityof extrapyramidal symptoms was similar to that reported in patientsreceiving the same doses of risperidone in the double-blind short-termstudies. No significant electrocardiographic changes or changes in vitalsigns (except for an increase in mean body weight) were observed inthe long-term studies. Increases in prolactin levels were reported; theassociation of these increases with adverse events is being investigated.Data from other studies still being analyzed will also be presented. Thelow incidence of serious adverse events in patients exposed to high dosesof risperidone for many months provides strong evidence that risperidoneis safe for long-term use.

IP-15-2! Weight Gain and long Term Clozapine Efficiency

I. 1alengues, I. Tauveron, E. Albuisson, V.Audy. Departments ofPsychiatry, Endocrinology, BiostatisticsCHU Saint-Jacques,Clermont-Ferrand, France

The aim of this study was to evaluate weight gain during clozap­ine treatment and determine possible relationship between psychiatricimprovement and weight gain.

Fifteen treatment-resistant schizophrenic inpatients were assessed byrating scales (BPRS, PANSS) for 21 months. Body weight was evaluatedbefore inclusion and at each subsequent psychiatric assessment after thebeginning of clozapine treatment.

In a tirst period, all patients presented with a significant improvementin total BPRS and other rating scales, reaching at 10 months a 58%decrease from initial value of BPRS. But in a second period, we clearlyidentified two patterns of evolution: in group 1, where patients experi­enced a marked improvement in symptoms of schizophrenia followedby subsequent stability, a regular weight gain was observed; in contrast,no significant weight profile was noted in group 2, where patients, afterinitial response for 10 months, experienced clinical instability whichrequired higher doses of clozapine.

These results can be considered as an argument in favor of a com­mon substratum to the clinically observed correlation between long-termantipsychotic efficiency of clozapine and weight gain.

IP-15-3[ Meg~co~on Associated with longterm NeurolepticMedication

H. Kazamatsuri, Y. Igarashi, Y. Mizutani, H. Habu. Tokyo MetropolitanMatsuzawa Hospital, Tokyo, Japan

Chronic constipation, ileus or megacolon are frequently seen amongchronically hospitalized psychiatric patients under long-term neurolepticmedication. We examined motility of bowels in 26 patients (14 male, 12female; average 54) who showed recurrent ileus by using "Sitzmark",