253 – First-episode schizophrenia and antibodies to Toxoplasma gondii

ABSTRACTS / Schizophrenia Research 98 (2008) 3–199 antipsychotic drugs, asenapine facilitates cortical glutamatergic transmission and cognitive function. Methods: Single-cell recording techniques were used to measure firing rate and burst firing of ventral tegmental area (VTA) dopamine neurons and in vivo microdialysis measured transmitter release in the nucleus accumbens (NAc) and prefrontal cortex (PFC) of rats. Local drug administration was performed using reverse microdialysis. Results: Asenapine dose-dependently (0.0005–0.2 mg/kg, iv) increased firing rate and burst firing of VTA dopamine neurons. Asenapine (0.1–0.2 mg/kg, sc) also increased dopamine output in the NAc as well as dopamine, noradrenaline and 5-HT output in the PFC. Local administration of asenapine increased dopamine, noradrenaline, and 5-HT output in the PFC, but did not affect dopamine output in the NAc. Intra-VTA tetrodotoxin perfusion blocked dopamine outflow in the NAc, but not PFC, induced by systemically administered asenapine. Conclusions: The asenapine-induced increase in NAc dopamine outflow seems dependent on and mediated by the increased dopamine neuronal activity. In contrast, facilitation of PFC dopamine outflow appears largely independent of dopamine neuronal activity and to depend on a local action at the nerve terminal. Given the known effects of selective ligands for 5-HT2A/2C receptors and α2 adrenoceptors on dopamine release in the PFC, the high affinity antagonism of these receptors by asenapine likely contributes to the increased prefrontal dopamine outflow. These data and our previous work further demonstrate the specific pharmacologic character of asenapine, as well as some of its similarities with clozapine, especially with regard to its effects in the PFC, which may have bearing on its effect on negative symptoms and cognitive dysfunctions. doi:10.1016/j.schres.2007.12.318

Miscellaneous 252 – LEEDS OUTCOME STAKEHOLDERS SURVEY (LOSS) J. Xia 1, C. Adams 1. 1

Cochrane Schizophrenia Group, Division of Psychiatry, University of Nottingham, Nottingham, UK Presenting Author details: [email protected] Division of Psychiatry, Duncan McMillan House, Portchester Road, NG3 6AA Nottingham, United Kingdom, Tel.: +44 (0)115 969 1300 X 48210. Background: There is variable attrition from randomized controlled trails (RCTs) evaluating treatments for the people with schizophrenia. Though most of these studies mention high attrition rates as a weakness, it is unclear at what degree of loss from such studies clinicians, researchers and service users or their careers begin to consider the results meaningless. Those undertaking systematic reviews do not have empirical data upon which to make decisions regarding the utility of such data as perceived by important stakeholders. Methods: Postal/e-mail survey – March 2006. Piloted questionnaire asking a single question regarding loss to follow-up in a schizophrenia trial. A sampling frame – 100 consultant psychiatrists from Yorkshire Deanery; 100 schizophrenia trialists whose e-mail is publicly available; 100 RETHINK service users.

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Results: This study is the first of its kind in health care. The main outcome measure will be a broad estimate of the acceptable level of drop-outs in schizophrenia drug trials as viewed by the different groups of stakeholders. This crude estimate will help encourage caution when interpreting results of trials where attrition exceeds this estimate. Clinicians, 55 ratings (43% response) and average answer is 75.3 (95% CI 72–78); Researchers, 32 ratings (32% response), average answer is 76.4 (95% CI 73–80); Service user, 81 ratings (76% response), average answer is 70.8 (95% CI 67–74). Conclusions: No significant differences were found between the three groups. doi:10.1016/j.schres.2007.12.319

253 – FIRST-EPISODE SCHIZOPHRENIA AND ANTIBODIES TO TOXOPLASMA GONDII S. Bachmann 1, R.H. Yolken 2, E.F. Torrey 3, J. Höffler 4, J. Schröder 5. 1 Klinik für Psychiatrie, Psychotherapie und Psychosomatik, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany 2 Stanley Division of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 The Stanley Medical Research Institute, Chevy Chase, MD, USA 4 St. Marien-Hospital, University of Witten-Herdecke, Hamm, Germany 5 Department of Psychiatry, University of Heidelberg, Heidelberg, Germany

Presenting Author details: [email protected] Julius-Kühn-Str.7, 06112 Halle (Saale), Germany, Tel.: +49 345 557 3624; fax: +49 557 3500. Background: Environmental risk factors for the development of schizophrenia include infections from the perinatal period onwards. Toxoplasma gondii (TG) is one of the candidate agents. A review (Torrey and Yolken., 2003) on TG in schizophrenia reported higher antibodies to TG in patients compared to controls in 18 of 19 studies including one by our group (Bachmann et al., 2005; Yolken et al., 2001). To replicate our preliminary results, we conducted an independent study. Methods: A sample of fifty-six patients presenting with their firstepisode of schizophrenia, schizophreniform or schizoaffective disorder and 32 age and gender matched control subjects were included. Standard instruments were used to assess diagnoses, psychopathology and screen controls. Sera were sampled once in controls and three times in patients during their hospitalization. Results: For the total sample contacts with animals during pregnancy and early age emerged as non-significant predictors of TG-IgG titers. Means of patients' and controls' TG-IgG titers did not differ significantly but variances did with IgG titers reaching much higher levels in a subgroup of patients than in controls. Patients in the high TG-IgG subgroup exhibited several trend level differences compared to the low TG-IgG subgroup including older age at onset. Moreover, several patients had decreasing IgG titers during hospitalization. A poweranalysis demonstrated that results fell short of significance due to lack of statistical power. Conclusions: We conclude that the sample size is the main reason for non-significant results. Based on the indicated power-analysis, we will

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ABSTRACTS / Schizophrenia Research 98 (2008) 3–199

perform an open label, multicenter study at regionally different sites within Germany. Acknowledgement: This work was supported by the Stanley Medical Research Institute.

255 – ANXIETY RELATED CONSTRUCTS IN EASTERN INDIAN HOSPITAL PATIENTS WITH BIPOLAR AND UNIPOLAR AFFECTIVE ILLNESSES K.R. Banerjee 1, T. Mitra 1.

doi:10.1016/j.schres.2007.12.320

254 – SOCIAL ANXIETY AND WITHDRAWAL IN HOSPITAL PATIENTS WITH SCHIZOPHRENIA: A STUDY IN INDIAN HOSPITAL SETTING K.R. Banerjee 1, T. Mitra 1. 1

National Institute of Behaviour Sciences, Department of Psychiatry, Kolkata, India Presenting Author details: [email protected] P7 C.I.T. Road, Moulali, 700014 Kolkata, India, Tel.: +91 33 32575411; fax: +91 33 22276177. Background: Social anxiety is a frequent but often unrecognized feature in schizophrenia .It is imperative to assess the impact, clinical correlates and consequences of social anxiety in schizophrenia so that treatment for these patients becomes more effective. Methods: A group of 70 outpatients with DSM-IV schizophrenia and a consecutive comparison group of 30 patients with comorbid social anxiety disorder along with schizophrenia were recruited from hospital psychiatry outdoor. The tests administered were the Liebowitz Social Anxiety Scale, Brief Fear of Negative Evaluation Scale, Self-esteem Evaluation Scale and the Scale for the Assessment of Positive Symptoms, Social Adjustment Scale and the Medical Outcomes Study 36-item Short-Form Health Survey. Results: The fear of negative evaluation was significantly higher (p = b0.05) in schizophrenia patients with comorbid social anxiety disorder. Schizophrenia patients without social anxiety disorder had significantly lower total scores on the Liebowitz Social Anxiety Scale and lower social and performance anxiety subscale scores. Social anxiety scores of schizophrenia patients with comorbid social anxiety disorder did not differ from those of subjects with social anxiety disorder as their primary diagnosis. No differences in negative and positive symptom rates were found between schizophrenia patients with and without social anxiety disorder. Schizophrenia patients with social anxiety disorder had a higher lifetime rate of suicide attempts. Social adjustment were significantly (p = b0.05) worse in comorbid social anxiety group. Conceivably self-esteem score was significantly lower (p = b0.05) in above group while compared to schizophrenia group. Conclusions: In this study, social anxiety appeared as a highly disabling condition in outpatients with schizophrenia. It can be conceivably deduce that in a country like India schizophrenic patients may be contending with social stigma. Thus more attention towards the deleterious implications of social anxiety in these patients may warrant better treatment outcome. Psychotherapies as cognitive– behavior therapy may be aimed to address this issue and to help these patients.

1

National Institute of Behaviour Sciences, Department of Psychiatry, Kolkata, India Presenting Author details: [email protected] P7 C.I.T. Road, Moulali, 700014 Kolkata, India, Tel.: +91 33 32575411; fax: +91 33 22276177. Background: The issue of comorbidity of anxiety and depressive disorders has been addressed frequently. Anxiety construct has a more defined association with unipolar (MDD) or a bipolar affective disorder (BPAD) in hospital patients of India is an intrigue question to answer. This plausibly can address the treatment efficacy as well. Methods: Total eighty (n = 80) outdoor patients with either MDD or BPAD were selected for the study. They were divided in equal numbers in each group. Patients were matched for age, sex, socioeconomic condition etc. Diagnosis was made by the chief psychiatrist of the hospital. The tests administered were State–Trait Anxiety Inventory (STAI), Brief Psychiatric Rating Scale (BPRS), the SCL-90 and the Schedule for the Assessment of Negative Symptoms (SANS) and Brief Fear of Negative Evaluation (BFNE). Appropriate statistical methods (Chi-Square, ANOVA, and Correlation) were used for analysis. Results: Social phobia were found in significantly higher proportion (p = b0.05) in MDD group. Obsessive symptoms were found more (not significant) in bipolar disorder. Overall, frequencies of panic disorder, OCD and social phobia were 26%, 25%, and 12%, respectively. Almost 40% affective disorder patients had single anxiety comorbidity and about 11% had two or more anxiety diagnoses. Negative evaluation was significantly higher in MDD group. Patients with multiple anxiety comorbidity had significantly higher scores than those without anxiety comorbidity on most SCL-90. Conclusions: Our observation indicates that anxiety construct were common accounting for about 50% of comorbidity among outdoor hospital patients. The panic disorder, OCD, and social phobia are common, occurring either singly or in mutual association in patients with affective disorders. While treating these patients intervention should be targeted to the comorbidity issue and thus more effective outcome may be expected. The psychotherapeutic approach should also take into account the anxiety construct of the affective disorder patients. doi:10.1016/j.schres.2007.12.322

256 – HETEROZYGOUS REELER MICE EXHIBIT ALTERATIONS IN SENSORIMOTOR GATING, BUT NOT PRESYNAPTIC PROTEINS A.M. Barr 1, K.N. Fish 2, A. Markou 3, W.G. Honer 1. 1

doi:10.1016/j.schres.2007.12.321

University of British Columbia University of Pittsburgh 3 University of California, San Diego 2