P.3 Psychotic disorders and antipsychotics S4-121 I P.3.055I Disturbed stress response in Multiple Complex Developmental Disorder andschizophrenia: Salivary cortisol response to a psychological stressor as a measure L.M.C.Jansen, PJ. Gademan,R.C.I. De Jonge, H. VanEngeland, R.S. Kahn , C.c. Gispen-de Wied. Rudolf Magnus Institute of Neuroscien ces. Department of Psychiatry . Utrecht Un iversity, Academic Hospital The hypothalamic-pituitary-adrenal system (HPA-system) is one of the biological systems responsible for the adaptation to stress. Impaired adaptation may lead to chronicstress. resulting in an alteredsetpointfor the HPA-systemand physiological stressresponse. Animalstudies show that stressfull eventsin early development are capable of disturbing the normal HPA-response to stressfulstimuliin later life (Fride et al. 1986). In this study, the HPA-system was studiedas a modelfor the adaptation of children with autistic-like disorders and schizophrenic patients to stress. Salivary cortisol was taken as a measureof HPAfunction. Multiple ComplexDevelopmental Disorder(MCDD) is an autistic-like disorder that is usually diagnosedin childhood. Some of the patients with MCDD develop schizophrenia in adulthood and an even larger part eventually develops a schizoid or schizotypal personality dis order. Therefore, MCDDmay be a precursorfor disorders in the schizophrenic spectrum (Van Engeland & Vander Gaag, 1994). Both MCDD and schizophrenia are described as developmental disorders, their devel- opment being influenced by environmental factors. For both disorders abnormal stress responses are described, suggesting a maladaptati on of the HPA-system. This may be a contributing factor to the vulnerability to decompensate under stressfull circumstances . It was hypothesized that similar dysfunctions in the HPA response to stress may exist in both MCDD and schizophrenia. 6 MCDDchildrenand 6 schizophrenic adults were each compared to 6 age and sexmatchedcontrolsin theirresponseto a psychological stress paradigm. Children were diagnosed according to the MCDDcriteria as described by Cohen et al. (1986) via the Maudsley Questionnaire. Adults were diagnosed according to DSM-IVcriteria for schizophrenia via the CASH interv iew. Positiveand negative symptoms were scored using the positive and negative symptomscale (PANSS) interview. HPA responses to the psychological stressor were measured on salivary cortisol. Heart rate was taken as a measure of autonomic arousal . Preliminary data show that psychological stress induces a significant rise in heart rate and salivary cortisol concentrations in healthy controls, for both children and adults. In MCDD and schizophrenic patients the cortisolresponseseemsto be diminished as compared to healthy controls. Finalresults will be presented. References Cohen, DJ., Paul, R.. Volkmar , HR. (1986) Issuesin the classi fi cation of Perva- sive and other developmental d isorders: toward DSM-IV. I. Am. Acad. Child Psychiatry 25, 213-220. Fride, E., Dan, Y., Feldon, I., Halevy, G., Weinstock, M. (1986) Eff ects of prenatal stress on vulnerability to stress in prepubertal and adult rats. Physio!. Behav, 37, 681--687. Van Engel and, H., Van derG aag, R.I. (1994) MeDD in cbildhood:ap recursor of schizophrenic spe ctrumdis orders . Schizophrenia Res earch I J, 197. I P.3.056I Treatment costs of schizophrenic patients E. Thys, M. De Hert,J. Peuskens, J. Boydens, K. Kesteloot, P.Gilis, L. Verhaegen. u.c. St-Jozef, Leuvensesteenweg 517, 3070 Kortenberg, Belgium Schizophrenia is a chronicdisorderthat hasconsiderable and long-lasting costs in terms of suffering, loss of incomeand other burdens on patients, families and society. In order to assess the costs of treatmentin Belgium(Flemish region) we followed 108 DSM-ill-R schizophrenic patients with schizophrenia recruited from different psychiatrists in 1994. Patients were classified according to their hospital status in 1993: ambulatory patients, at least one admission or discharge and continuous hospitalization. The sex dis- tribution was equal. Three agebands were also determined: < 30, 30-40 and > 40 years. Direct costs and differentclinical and outcomevariables were evaluated. Patients were interviewed in 1995and the assessmentof costs was retrospective . The costs were calculatedfrom the viewpoint of both the healthinsurance and the patients. The mean age was 36.4 (sd 10.6) years. The mean duration of illness was 14 years and patients were hospitalized 5.0 (sd 3.2) times on the average. 75% of patients had a lifetime duration of hospital stay of more than 2 years. 79% of the patients were unemployed and 86%, withoutpartner. 58% of patients havespent sometimein hospitalin 1994. The mean neurolep- tic dose was 8.0 mg (sd 6.3) haldol equivalent and 41% were on depot medication. The annual direct treatment costs of ambulatory patients and hospital- ized patients differed significantly, respectively 2,084 USD (I USD = 30 BEF) and 44,813 USD (p < 0.001).There were no significant differences related to costs between male and female patients and between the different agebands. A simulation taking into account the actual distribution and an esti- mated total numberfor Belgiumof schizophrenic patientsof N = 25,274 gives us an estimateof annual total direct treatment costs of 304 million USD.The state expenditure for the treatmentof schizophrenia is 1.9% of the health expenditure of the Belgian government This study was supported by a grant from Eli Lillyand Company. I P.3.057I Stimulation of serotonin (5-HT)'A autoreceptors enhances dopamine (DA)and noradrenaline {NAD} refease in rat frontal cortex: influence of S 15535, WAY 100,635 and8-OH·DPAT F. Lejeune, A. Gobert, I.-M . Rivet, A. Newman-Tancredi, V. Audinot, MJ. Millan. lnstitut de Rech erches Servier, Centre de Recherches de Croissy ; Department of Psychopharmacology, 125Chemin de Ronde, F-78290 Croi ssy-sur-Seine, Paris, France A perturbation of doparninergic, adrenergic and serotoninergic input to the frontal corteX is implicated in the pathology of depression and other psychiatric diseases. Correspondingly, it is important to understand interrelationships amongst these pathways. Serotonin IA receptors are of interestinasmuch as they modulate the activity of doparninergic pathways and are implicated in these disorders. However , the role of pre- as com- pared to post-synapticsites is unclear . Weaddressed this issue employ- ing: 8-hydroxy-2-(di-n-propylamino) tetralin (8-0 H-DPAT), an agonist at pre and postsynaptic 5-HT 1A receptors; (N-{2-[4-(2-methoxyphenyl)- l-piperazinyl] ethyl}-N-(2-pyridinyl) cyclo-hexanecarboxamide (WAY 100,635), an antagonist at pre- and post-synaptic 5-HT 1 A sites and (4- (benzodioxan-5-yl)1-(indan-2-yl )piperazine) (S 15535), an agonist at pre-, and an antagonist at post-synaptic 5-HT 1A receptors. Membranes from CHOcells transfected with human(h) 5-HT 1A , hD2' hD:l and ha2A receptors were used. Radioligands were [3H]8-0H-DPAT for h5-HT 1A (1.0 oM), [ 125 I]iodosulpiride for hD 2 (0.1 oM) and hD3 (0.2 oM) and [3H]RX 821,002(0.7 oM) for 002A receptors, respecti vely. Firingrates of dorsal raphe nucleus CORN) and ventrotegmental (VTA) dopaminergi c neurones were measured with a tungstenelectrode in male Wislarrats (200-220 g) anaesthetised withchloralhydrate(400.0 mglkg, i.v.). Fordialysis, rats wereimplanted I weekpre-testing witha probe in frontal cortex and samples takenevery 20 min. Sampleswere analysed by coulometric detectionIHPLC. Drugs were dissolvedin sterilewater. S 15535 , 8-0H-DPAT and WAY 100,635 were selective ligandsat 115- HT 1A receptors (Table I). S 15535 mimicked the 8-0H-DPAT-induced reduction in DRN firing rate and cortical 5-HTrelease, as well as the 8-0H-DPAT-induced stimulation of VTAfiring rate and increasein corti- Table I -- Ki (oM ) ... -- M inimal effective dose (JLg/kg) ... h5-RT IA bD2 so, ha2A ,j, D RN tVTA ,j, 5-HT t DA t NAD S ISS35 0.7 400 248 190 2 125 630 630 630 8·0H·DPAT 0.6 1746 361 1870 0.2 20 20 20 20 WAY 100,635 0.6 175 222 :> 10.000 > 1000 >1000 >630 >630 >630 DRN = d orsal raphe nuclei ; VTA = ventrotegmental area. Doses are in JLglkg base, i.v, for decreases in firing rate (DRNNTA), and in JLglkg base, s.c. for decreases in cortical serotonin (S-RT) rel ease and increases in cortical dopamine (DA) and noradrenaline (NAD) release.