forebrain regions. However, asenapine was more potent, with ED50

values consistently lower than those of olanzapine and risperidoneacross all forebrain regions examined. In addition, asenapine displayedpreferentially higher affinity for D1 and D2 receptors in MPC (ED50,0.018 and 0.004 mg/kg, respectively), DFC (0.015 and 0.003 mg/kg),and HIPP (both 0.014 mg/kg) than in CPu (both 0.03 mg/kg), NAc(0.044 and 0.024 mg/kg), or EC (0.064 and 0.017 mg/kg). In contrast,both olanzapine and risperidone occupied D1 and D2 receptors indifferent forebrain regions with similar ED50 values.Discussion: These findings suggest that the profile of asenapine-induced D1 and D2 receptor occupancy is different from that ofolanzapine and risperidone. Preferential occupancy of D1 and D2receptors by asenapine in cortical and limbic versus extrapyramidalbrain regions supports the unique psychopharmacologic propertiesof this novel antipsychotic agent. (Supported by HD-052752 andSchering Corp., a division of Merck & Co.)

doi:10.1016/j.schres.2010.02.976

Poster 216ALTERATION OF AKT1 AND NEUREGULIN-1 GENE EXPRESSION INFRONTAL CORTEX AND DENTATE GYRUS MAY BE ASSOCIATEDWITH SCHIZOPHRENIA: PERINATAL ASPHYXIA MODEL IN RAT

Tomoyasu Wakuda1, Shiro Suda2, Keiko Iwata2, Katsuaki Suzuki2,Norio Mori1, Nori Takei2,31Department of Psychiatry and Neurology, Hamamatsu UniversitySchool of Medicine Hamamatsu, Shizuoka, Japan; 2Research Center forChild Mental Development, Hamamatsu University School of MedicineHamamatsu, Shizuoka, Japan; 3the Institute of Psychiatry LondonUnited Kingdom

Background: Many previous studies have reported an associationbetween obstetric complications (OCs) and the later develop-ment of schizophrenia. One of the mechanisms underlying theassociation is postulated to be a hypoxic process in the brain in theoffspring around the time of birth. AKT1 and neuregulin-1 (NRG1)are putative candidate genes for susceptibility to schizophrenia.Both AKT1 mRNA and protein expression have been shown to bereduced, and NRG1 isoforms to be differentially expressed in brainregions of schizophrenia patients such as the prefrontal cortex andhippocampus (Emamian et al. 2004; Thiselton et al. 2008;Hashimoto et al. 2004). Moreover, the expression of these twogenes (i.e, AKT1 and NRG1) is liable to ischemia/hypoxia. Inischemia/hypoxia-induced adult rodents, the expression of AKT1and NRG1 that act as a neuroprotective agent has, in effect, beenshown to be elevated. In our animal model in which neonates wereexposed to hypoxia, we postulated that these two genes would beexpressed differentially even in adulthood, i.e., the risk period ofmanifestation of psychosis in humans.Methods: In this study, we exposed neonatal pups to hypoxia for15 min and, then, measured the AKT1 and NRG1 mRNA levels in theprefrontal cortex, dentate gyrus and hippocampus of these grown-up rats using quantitative PCR.Results: Significantly decreased mRNA levels of AKT1 wereobserved in hypoxia-exposed rats (n=6) compared with unex-posed rats (n=6): a 48% reduction for the prefrontal cortex(p<.011), 48% for the dentate gyrus (p<.001), and 55% for thehippocampus (p<.01). NRG1 mRNA expression was also decreasedin the prefrontal cortex (a 85% reduction, p<.018) and the dentategyrus (69%, p<.049), but not in the hippocampus (p=.11), for thehypoxia-exposed rats compared with unexposed rats.Discussion: These results suggest that perinatal asphyxia maylead to disturbances in various brain regions, including the

prefrontal cortex, dentate gyrus, and hippocampus, which in turnexert a long-lasting influence on the expression of specific genessuch as AKT1 and NRG1. There is evidence in support of aninvolvement of AKT1 in schizophrenia. Alterations in AKT1-GSK3bsignaling have been associated with schizophrenia (Emamian etal. 2004). Furthermore, AKT1 knockout mice shows impairedprepulse inhibition (PPI) of acoustic startle response; PPI deficitsare thought to be one of endophenotypes for schizophrenia. Asregards NRG1, NRG1-erbB signaling has also been linked withschizophrenia. Interestingly, loss of erbB signaling in oligoden-drocytes alters dopaminergic function (Roy et al. 2007), andsimilar alterations of dopaminergic function have been demon-strated in our previous study of the perinatal asphyxia model(Wakuda et al. 2008). Our findings of altered expression of AKT1and NRG1 genes may provide a biological basis for understandingthe elusive association between a history of OCs and thedevelopment of schizophrenia.

doi:10.1016/j.schres.2010.02.977

Poster 217HIPPOCAMPAL DYSFUNCTION IN A MATERNAL IMMUNEACTIVATION (MIA) ANIMAL MODEL OF SCHIZOPHRENIA

Amy R. Wolff, Kirsten R. Cheyne, David K. BilkeyUniversity of Otago Dunedin, Otago, New Zealand

Background: Cognitive impairments are recognized as a key aspectof schizophrenia and may result from deficits in the formation andmaintenance of contextual representations. Previous researchindicates that the hippocampus processes contextual informationand that hippocampal function is abnormal in schizophrenia. Ourstudy examined hippocampal function in rats using the maternalimmune activation (MIA) animal model of schizophrenia. MIAmodels the relationship between exposure to prenatal infection andthe increased risk of developing schizophrenia in the offspring. Thematernal response to infection may be a critical factor in thatcytokines are thought to alter neurodevelopmental processes so asto increase the risk of schizophrenia.

Methods: The MIA model induces an immune response with asingle injection of the synthetic cytokine activator (polyinosinic-polycytidilic acid) administered to pregnant rat dams during mid-gestation. MIA offspring were examined in a number of behaviouraltasks affected by damage to the hippocampus, or its input structures,to test for hippocampal dysfunction related to schizophrenia. Aseparate group of animals were implanted with electrodes in areaCA1 of the hippocampus. Recordings were conducted in awake freelymoving animals to directly monitor hippocampal neuronal activity.Results: MIA animals displayed significantly increased locomo-tion during open-field exploration. This hyper-locomotor behaviourwas observed in adult, but not juvenile MIA offspring, mimickingthe post-pubertal emergence of schizophrenic symptoms. MIAanimals also spent less time exploring objects in an open-field(p<0.001) and the proportion of time exploring novel rather thanfamiliar objects was less than in controls (p<0.05), despite normalobject discrimination performance. The MIA manipulation alsoresulted in abnormally rapid reversal of a spatial discrimination in asubmerged T-maze (p<0.05). During exposure to a novel environ-mental context, MIA offspring showed more rapid within-trialhabituation of rearing than control animals (p<0.05), suggestingthat that MIA offspring encode contextual information about anovel experience abnormally relative to control animals. Prelimin-ary analysis of electrophysiological recordings of hippocampalneurons was also indicative of abnormal hippocampal processing,

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with cells in MIA offspring displaying higher spatial informationcontent and coherence (p<0.01) and a lower average firing rate(p<0.01) and smaller place fields (p=0.05) than control animals.Discussion: The current study describes a range of cognitive deficitsthat have not previously been observed in the MIA rat model, andreplicates the previous finding of enhanced reversal learning in MIArats. MIA animals displayed abnormalities during exploration of anopen-field, spatial discrimination reversal learning, and novelobject recognition. These deficits are linked, in that they havepreviously been associated with damage to the hippocampus or itsimmediate afferents. Our finding that the MIA offspring displayedabnormally rapid habituation of rearing during exposure to a novelenvironmental context suggests that MIA animals may be abnor-mally processing contextual information in the hippocampus. Wealso found electrophysiological evidence of abnormal activity inhippocampal neurons in MIA offspring. Together, these resultssupport proposals that changes within this region underlie corecognitive deficits in schizophrenia.

doi:10.1016/j.schres.2010.02.978

Poster 218SOUTH ASIANS' ATTITUDES TOWARDS COGNITIVE REMEDIATIONAFTER FIRST EPISODES OF PSYCHOSIS

Claire J. Press, Richard J. Drake, Nusrat HusainThe University of Manchester Manchester, Greater Manchester,United Kingdom

Background: A fourfold increase in incidence of psychosis has beenestablished in migrant groups; incidence rates among UK secondgeneration ethnic minorities are higher. Differences in explanatorymodels and pathways to care have been demonstrated for SouthAsian psychosis sufferers compared to other ethnicities. There areconcerns that ethnic minorities have difficulty accessing andengaging with psychiatric services. Cognitive Remediation (CR) isan effective intervention for schizophrenia but its acceptability andaccessibility amongst minority groups have not been examined.This qualitative study explored attitudes towards CR and otherpsychological interventions among UK first episode schizophrenia(FES) sufferers of South Asian ethnicity.Methods: Ten FES patients from NHS Early Intervention Services inNorth West England were digitally audio-recorded during face-to-face semi-structured interviews, analysed using framework analysis.Results: The main themes emerging from the initial analysis includedparticipants': pathways to care; attitudes towards their currentsupport; and views on the acceptability and possible adaptations toCR. Participants received help from a combination of friends, families,religious leaders, NHS and voluntary sector services. Nine were takingantipsychotic medication. The majority had followed the recommen-dations of a community elder or Imam. Three out of 10 participantshad been offered a psychosocial intervention for psychosis: two hadbegun, but withdrew from cognitive behavioural therapy; and oneintermittently attended family intervention sessions. None werereceiving any psychosocial support at the time of interview. Allreported memory and concentration deficits and a wish to improvetheir cognitive skills. A trial session of computerized CR was wellreceived. All participants were multilingual but chose to conduct theinterview in English. All dismissed the need to translate CR programtasks into another language. Many recommended simple adaptationsto its content such as removing references to non-Halal foods.Discussing CR delivery, the majority favoured multiple sessions perweek, based at home, with 1:1 support from a therapist. Thetherapist's gender, culture or ethnicity was unimportant.

Discussion: This young, moderately acculturated cohort exhibitedmultiple pathways to care highly influenced by family attitudes andreligious beliefs. Minor changes to the content of the CR program andensuring the therapist is sensitive to cultural factorsmay further improvethe accessibility and acceptability of this intervention. Previouslyreported cultural barriers such as language and therapist traits werenot replicated. CR proved to be highly acceptable to this group.

doi:10.1016/j.schres.2010.02.979

Poster 219COGNITIVE DEFICIT IN SCHIZOPHRENIA AND ITS REMEDIATION

Hana Prikrylova Kucerova, Helena Fejfarova, Petra Navratilova,Radovan PrikrylDepartment of Psychiatry, Medical Faculty Masaryk University andFaculty Hospital Brno, Jihlavska 20 Brno Czech Republic

Background: Cognitive functions and their disruption belong tomain characteristics of schizophrenia and it chiefly influences theprocess and the functional final stadiums of this disorder. Finalstage of the disease can be influenced by pharmacotherapy onlyindirectly and its influence on the cognitive functions is onlylimited. For that reason new possibilities how to adjust thecognitive deficit are being searched. One of these possibilities isneuropsychological rehabilitation of cognitive functions by PCsoftware programme (O. Bracy - PSSCogRehab).Methods: PC software programme (O. Bracy: PSSCogRehab) forrehabilitation of cognitive functions was used. It is a multimedialsoftware, it consists of 8 moduls with modified parameters comprisedof 64 tasks, gradually increasing difficulty from attention domains,visuospatial and memory tasks to executive skills, and situationsolving, individual settings, laterality and flexibility training, pre- andpost-study neuropsychological and clinical assessment, 8 weeksduration, 3 interventions per week (total 24) 90 min each, trainingconducted by a clinical psychologist. Our cohortwas formed of 10manwith the first episode of schizophrenia (F 20.0 according to ICD-10).Results: Statistically improvement (t-test) was found in verbalworking memory variables and in some variables of attention.Discussion: After 8 weeks neuropsychological treatment usingPSSCogRehab we could see improvement in all domains of cognitivefunction, in some memory and attention variables this effect wasstatisticaly significant. We can generalized that PC programme hasimpact on specific areas of cognitive functions.

doi:10.1016/j.schres.2010.02.980

Poster 220MOBUS PROJECT – RANDOMISED STUDY OF AN ASSISTIVETECHNOLOGY FOR IMPROVING COGNITION ANDAUTONOMY OF PATIENTS WITH SCHIZOPHRENIA:EXPLORING PRILIMINARY DATA

Juliette Sablier1,2,3,4, Emmanuel Stip1,2, Nicolas Franck3,4,Mobus Group1,2,3,41University of Montreal Montreal, Quebec, Canada; 2Fernand SeguinResearch Center of Louis-H. Lafontaine Hospital Montreal, Quebec,Canada; 3University of Lyon Lyon France; 4Center of CognitiveNeuroscience, UMR5229CNRS Lyon France

Background: Cognitive impairments in schizophrenia lead to anegative functional outcome. Especially, deficits in memory and

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