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P.3.a.016 Depressive dimension in acute schizophrenic inpatients and its impact on clinical outcome
S394
P.3.a Psychotic disorders and antipsychotics – Psychotic disorders (clinical)
Method: Adult outpatients 18−75 years of age with schizophrenia who maintained clinical stability on open-label oral olanzapine (10, 15, or 20 mg/day) for 4 consecutive weeks were randomized to 24 weeks of double-blind treatment with OLAI at doses of 150 mg/2 weeks (N = 140), 405 mg/4 weeks (N = 318), or 300 mg/2 weeks (N = 141); to a low reference dose of 45 mg/4 weeks (N = 144); or to oral olanzapine at their previously stabilized dose (N = 322). No oral antipsychotic supplementation was permitted. Clinical stability was defined as 1) no change of oral olanzapine dose; 2) Clinical Global Impressions-Improvement of Illness (CGI-I) score 4; and 3) Brief Psychiatric Rating Scale (BPRS) Positive score 4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) total and subscales, PANSS-derived BPRS total score and subscales, and the Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-I scales. Results: Mean baseline-to-endpoint changes in PANSS total scores using last-observation-carried-forward (LOCF) methodology for patients treated with therapeutic OLAI doses (300 mg/2 weeks, 405 mg/4 weeks, 150 mg/2 weeks) differed significantly from those treated with OLAI 45 mg/4 weeks (respectively, −2.2, −0.1, 2.7 vs. 7.3; all p < 0.001). Significant separation between the OLAI 300 mg/2 weeks, 405 mg/4 weeks, 150 mg/2 weeks groups versus the 45 mg/4 weeks group in PANSS total scores was observed starting at 3, 2, and 11 weeks, respectively, and maintained through the end of the study (p < 0.05). Similar differences between therapeutic OLAI doses and the 45 mg/4 weeks dose were observed for the BPRS total, CGI-I, and CGI-S scores. Mean baseline-to-endpoint change in PANSS total score for the oral olanzapine group was −1.7, which was not significantly different from that of the highest OLAI dose group (300 mg/2 weeks = −2.2; p = 0.606) but superior to the other OLAI doses (p’s <0.01). Incidence of weight gain 7% of baseline was significantly greater for oral olanzapine (21.4%), OLAI 300 mg/2 weeks (20.7%), 405 mg/4 weeks (15.2%), and 150 mg/2 weeks (16.4%), compared with OLAI 45 mg/4 weeks (8.3%, all p.05). There were no clinically meaningful differences between OLAI and oral olanzapine with respect to laboratory measures, vital signs, ECGs, or extrapyramidal symptoms. Incidence of injectionsite reactions was low (2.8%). Two patients treated with OLAI experienced post-injection delirium/sedation syndrome following possible inadvertent intravascular injection. Conclusions: Maintenance treatment with OLAI at doses of 150 mg/2 weeks, 405 mg/4 weeks, and 300 mg/2 weeks was more efficacious than a 45 mg/4 weeks dose in preventing the deterioration of symptoms in patients with schizophrenia for up to 24 weeks. The safety profile for these OLAI doses was consistent with that of oral olanzapine [2] except for injection-related events. References [1] Kane, J.M., 2006 Review of treatments that can ameliorate nonadherence in patients with schizophrenia. J Clin Psychiatry 67(Suppl 5), 9−14. [2] Tran, P.V., Dellva, M.A., Tollefson, G.D., Wentley, A.L., Beasley, C.M. Jr., 1998 Oral olanzapine versus oral haloperidol in the maintenance treatment of schizophrenia and related psychoses. Br J Psychiatry 172, 499–505.
P.3.a.016 Depressive dimension in acute schizophrenic inpatients and its impact on clinical outcome M.C. Mauri1 , A. Colasanti1 ° , A. Mazzocchi1 , F. Pellegrino1 , D. Moliterno1 , M. Rossattini1 , A.C. Altamura1 . 1 Clinical Psychiatry, Clinical Psychiatry IRCCS Foundation Ospedale Maggiore Policlinico, Milan, Italy Data from literature showed the existence of different symptoms clusters in Schizophrenia, one of which is the depressive cluster, representing an important and distinct symptom domain in Schizophrenic Disorder. Depressive symptoms may occur at any time during the illness and are most frequently associated with the acute phase of the illness, with studies suggesting a prevalence from 22% to 80% [1]. In our study we extract clusters of symptoms in acute hospitalized patients affected by Schizophrenia, using factor analysis. The aim of this research is to find a relationship between the depressive dimension in hospitalized patients with schizophrenia in acute phase, and their clinical outcome at discharge. The data were drawn from a prospective, naturalistic, observational study of schizophrenic patients consecutively admitted to a psychiatric ward, during a re-exacerbation phase. Psychiatric diagnoses were formulated on the basis of the Diagnostic and Statistical manual of Mental disorder, 4th edition (DSM IV) criteria. The 24 items Brief Psychiatric Rating Scale (BPRS) was administered at baseline (T0) and at discharge (T1). Statistics consisted in descriptive analyses, T-Test for Repeated Measures, and Principal Component Factor Analysis with Varimax Rotation of the BPRS scores at T0. Factor scores obtained were consequently computed as separate variables. Spearman non-parametric correlation analyses were performed between factor scores, amelioration in BPRS scores, and duration of hospitalization. 183 patients (140 M, 43 F) were included in the study. The mean age was 42.2 years±11.2 SD. The mean duration of hospitalization was 12 days±8.6. The BPRS scores showed a significant improvement at T1 compared to T0 (39.11±9.6 SD vs 54.89±13.8 SD, p < 0.0001). The factor analysis of BPRS scores at T0 extracted 4 Principal Factors: Depression/Anxiety, Resistance/Positive symptoms, Negative symptoms, and Activation. The Depression/Anxiety dimension was primarily determined by anxiety, depression, somatic concern and suicidal risk. The 49.2% of variance was explained by the factor analysis. The percentage of amelioration in BPRS scores was positively correlated to Depression/Anxiety score (r = 0.2; p < 0.005). Higher scores in the Depression/Anxiety dimension were related to a longer duration of hospitalization. Nevertheless, the percentage of amelioration measured by BPRS was not significantly related to the duration of hospitalization. As previous studies [2] showed, our research confirms that symptoms in Schizophrenia cluster together in distinct domains, one of which represented by Depression/Anxiety dimension. We found that patients with acute episode of schizophrenia presenting with a more relevant depressive component have a better outcome than the others. This fact could be due to a greater awareness of illness and a worse subjective state that improve their compliance to therapeutic projects. The relationship between the presence of depression and longer duration of hospitalization could be explained by the fact that doctors perceive depressed patients as more needing in terms of cares than no-depressed ones.
P.3.a Psychotic disorders and antipsychotics – Psychotic disorders (clinical) References [1] Emsley, R.A, Oosthuizen, P.P., Joubert, A.F., Roberts, M.C., D.J. Stein, 1999 Depressive and anxiety symptoms in patients with schizophrenia and schizophreniform disorder. J Clin Psych 60, 747–751. [2] Ventura, J, Nuechterlein, K.H., Subotnik, K.L., Gutkind, D., Gilbert, E.A. 2000 Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale. Psych Res 97, 129–135
P.3.a.017 Decreased serum proBDNF/BDNF ratio in patients with schizophrenia
S395
ratio was found in patients with schizophrenia in comparison with healthy controls (p < 0.05). Conclusions: Firstly, this study demonstrated that proBDNF can be measured in human serum and that the proBDNF/BDNF ratio is altered in patients with schizophrenia. We hypothesized that abnormal proteolitic processes occurring in schizophrenia brains may lead to decreased proBDNF/BDNF ratio, thus affecting neuronal plasticity. We will further explore whether proBDNF/BDNF ratio correlates with cognitive performances; also, we will investigate the effect of antipsychotics (typicals vs atypicals) on the serum proBDNF/BDNF ratio in patients with schizophrenia. References
D. Carlino1 ° , E. Leone2 , E. Tongiorgi2 , M. De Vanna1 . 1 Psychiatric Clinic University of Trieste, Department of Clinical Morphological and Technological Sciences, Trieste, Italy; 2 B.R.A.I.N. Centre for Neuroscience University of Trieste, Department of Biology, Trieste, Italy Objectives: Brain Derived Neurotrophic Factor (BDNF), a member of the family of neurotrophins (NTs), is central to many facets of CNS function, from differentiation and neuronal survival to synaptogenesis and activity-dependent forms of synaptic plasticity. Several studies demonstrated that abnormal BDNF levels are involved in the pathophysiology of schizophrenia. Conversely, there are no studies investigating the role of BDNF’s precursor (proBDNF) in this disorder. Indeed, proBDNF as well as the other pro-NTs is crucial in signalling pathways by interacting with the p75 neurotrophin receptor (p75NTR). Interestingly, proneurotrophins seem to have biological effects that oppose those of mature neurotrophins, promoting apoptosis and Long Term Depression (LTD). Therefore, the proteolytic cleavage of proneurotrophins could represent a mechanism that controls the direction of action of neurotrophins and the altered balance of these two forms may determine abnormal brain functions. Based on this evidence, we measured by western blot proBDNF/BDNF ratio in human serum. Then we compared this ratio in patients with schizophrenia and healthy controls. Methods: 40 patients with a DSM-IV-TR diagnosis of schizophrenia and 40 aged and gender matched healthy volunteers were investigated. For serum samples preparation, blood (5 ml) was collected in anticoagulant-free tubes and maintained at room temperature for 1 hour, followed by 1 hour at 4ºC to allow complete release of Brain Derived Neurotrophic Factor from platelets. Finally, serum was isolated by centrifugation at 2000 g for 10 min at 4ºC. Total serum Brain Derived Neurotrophic Factor (ng/mL) was measured by using a specific ELISA kit (BDNF Emax imuunoassay system, Promega Co, USA). Subsequently western blot was used to detect both mature and precursor form of Brain Derived Neurotrophic Factor using a specific antiBDNF antibody (N-20 Santa Cruz, USA). The antibody specificity, previously demonstrated in human brain, was ensured in human serum by competitive Western blot. Relative amounts of proBDNF/BDNF ratio in schizophrenic patients and healthy volunteers were determined by densitometry of the immunoreactive bands. The Sigma Stat 3.1 Software was used for all statistical analysis. A two tailed statistical significance was set at p < 0.05. A One-way ANOVA was conducted to detect the between group differences in total serum Brain Derived Neurotrophic Factor and proBDNF/BDNF. Results: There were no statistically significant differences between patients with schizophrenia and healthy controls (p = 0.558) in terms of total serum Brain Derived Neurotrophic Factor. On the contrary, a significant reduction of serum proBDNF/BDNF
[1] Woo, N.H., Teng, H.K., Siao, C.J., Chiaruttini, C., Pang, P.T., Milner, T.A., Hempstead, B.L., Lu, B., 2005, Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8, 1069–1077. [2] Shimizu, E., Hashimoto, K., Watanabe, H., Komatsu, N., Okamura, N., Koike, K., Shinoda, N., Nakazato, M., Kumakiri, C., Okada, S., Iyo M., 2003, Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls. Neurosci. Lett. 351, 111–114. [3] Volosin, M., Song, W., Almeida, R.D., Kaplan, D.R., Hempstead, B.L., Friedman, W.J., 2006, Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 19, 7756–7766.
P.3.a.018 Changes in antisaccadic test, gain and negative symptoms in schizophrenic patients treated with glycine D. Strzelecki1 ° , J. Rabe-Jablonska1 . 1 Medical University of Lodz, Department of Affective and Psychotic Disorders, Lodz, Poland Purpose of the study: Glutamatergic NMDA (N-methyl-Daspartate) receptor plays an important role in cognitive processes as visuo-spatial attention and visuo-motor skills and also participate as a glutamatergic ionotropic receptor in mechanisms of control of other neurotransmitter systems as e.g. dopaminergic, adrenergic or serotoninergic system. Glycine – simple aminoacid, is a natural coagonist of NMDA receptor necessary in its proper and effective functioning. According to hypoNMDA hypothesis treatment with high doses of glycine (max. 60g per day per os) can increase function of NMDA receptor and improve primary negative symptoms in schizophrenia and also normalize eye movements, which are commonly disturbed in majority of schizophrenic patients and their families. The work objective was evaluation of glycine influence on eye movements in schizophrenia as an augmentation of antipsychotic treatment with typical or/and atypical drugs. Methods: Twenty eight patients with predominant negative symptoms (mean 25.7 points in PANSS Negative symptom subscale) in stable clinical condition and stable antipsychotic medication for min. 3 months, had completed 6 weeks, prospective, open label study (Thirty two patients was enrolled). Between visits 1 and 2 (weeks 0 and 6) patients received solution of glycine in high oral doses (0.8 g/kg/day/2 doses) with previous typical or/and atypical antipsychotic treatment. On both visits glycine influence on eye movements was assessed based on: 1) Eye tracking (gain in 3 velocities of object: 29, 38 and 49º/s), 2) Saccadic task (latency, time of saccade) and 3) Antisaccadic task (number of errors in task). Additionally we rated intensity of schizophrenic symptoms using PANSS.
P.3.a Psychotic disorders and antipsychotics – Psychotic disorders (clinical)
Method: Adult outpatients 18−75 years of age with schizophrenia who maintained clinical stability on open-label oral olanzapine (10, 15, or 20 mg/day) for 4 consecutive weeks were randomized to 24 weeks of double-blind treatment with OLAI at doses of 150 mg/2 weeks (N = 140), 405 mg/4 weeks (N = 318), or 300 mg/2 weeks (N = 141); to a low reference dose of 45 mg/4 weeks (N = 144); or to oral olanzapine at their previously stabilized dose (N = 322). No oral antipsychotic supplementation was permitted. Clinical stability was defined as 1) no change of oral olanzapine dose; 2) Clinical Global Impressions-Improvement of Illness (CGI-I) score 4; and 3) Brief Psychiatric Rating Scale (BPRS) Positive score 4 on each of the following items: conceptual disorganization, suspiciousness, hallucinatory behavior, and unusual thought content. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) total and subscales, PANSS-derived BPRS total score and subscales, and the Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-I scales. Results: Mean baseline-to-endpoint changes in PANSS total scores using last-observation-carried-forward (LOCF) methodology for patients treated with therapeutic OLAI doses (300 mg/2 weeks, 405 mg/4 weeks, 150 mg/2 weeks) differed significantly from those treated with OLAI 45 mg/4 weeks (respectively, −2.2, −0.1, 2.7 vs. 7.3; all p < 0.001). Significant separation between the OLAI 300 mg/2 weeks, 405 mg/4 weeks, 150 mg/2 weeks groups versus the 45 mg/4 weeks group in PANSS total scores was observed starting at 3, 2, and 11 weeks, respectively, and maintained through the end of the study (p < 0.05). Similar differences between therapeutic OLAI doses and the 45 mg/4 weeks dose were observed for the BPRS total, CGI-I, and CGI-S scores. Mean baseline-to-endpoint change in PANSS total score for the oral olanzapine group was −1.7, which was not significantly different from that of the highest OLAI dose group (300 mg/2 weeks = −2.2; p = 0.606) but superior to the other OLAI doses (p’s <0.01). Incidence of weight gain 7% of baseline was significantly greater for oral olanzapine (21.4%), OLAI 300 mg/2 weeks (20.7%), 405 mg/4 weeks (15.2%), and 150 mg/2 weeks (16.4%), compared with OLAI 45 mg/4 weeks (8.3%, all p.05). There were no clinically meaningful differences between OLAI and oral olanzapine with respect to laboratory measures, vital signs, ECGs, or extrapyramidal symptoms. Incidence of injectionsite reactions was low (2.8%). Two patients treated with OLAI experienced post-injection delirium/sedation syndrome following possible inadvertent intravascular injection. Conclusions: Maintenance treatment with OLAI at doses of 150 mg/2 weeks, 405 mg/4 weeks, and 300 mg/2 weeks was more efficacious than a 45 mg/4 weeks dose in preventing the deterioration of symptoms in patients with schizophrenia for up to 24 weeks. The safety profile for these OLAI doses was consistent with that of oral olanzapine [2] except for injection-related events. References [1] Kane, J.M., 2006 Review of treatments that can ameliorate nonadherence in patients with schizophrenia. J Clin Psychiatry 67(Suppl 5), 9−14. [2] Tran, P.V., Dellva, M.A., Tollefson, G.D., Wentley, A.L., Beasley, C.M. Jr., 1998 Oral olanzapine versus oral haloperidol in the maintenance treatment of schizophrenia and related psychoses. Br J Psychiatry 172, 499–505.
P.3.a.016 Depressive dimension in acute schizophrenic inpatients and its impact on clinical outcome M.C. Mauri1 , A. Colasanti1 ° , A. Mazzocchi1 , F. Pellegrino1 , D. Moliterno1 , M. Rossattini1 , A.C. Altamura1 . 1 Clinical Psychiatry, Clinical Psychiatry IRCCS Foundation Ospedale Maggiore Policlinico, Milan, Italy Data from literature showed the existence of different symptoms clusters in Schizophrenia, one of which is the depressive cluster, representing an important and distinct symptom domain in Schizophrenic Disorder. Depressive symptoms may occur at any time during the illness and are most frequently associated with the acute phase of the illness, with studies suggesting a prevalence from 22% to 80% [1]. In our study we extract clusters of symptoms in acute hospitalized patients affected by Schizophrenia, using factor analysis. The aim of this research is to find a relationship between the depressive dimension in hospitalized patients with schizophrenia in acute phase, and their clinical outcome at discharge. The data were drawn from a prospective, naturalistic, observational study of schizophrenic patients consecutively admitted to a psychiatric ward, during a re-exacerbation phase. Psychiatric diagnoses were formulated on the basis of the Diagnostic and Statistical manual of Mental disorder, 4th edition (DSM IV) criteria. The 24 items Brief Psychiatric Rating Scale (BPRS) was administered at baseline (T0) and at discharge (T1). Statistics consisted in descriptive analyses, T-Test for Repeated Measures, and Principal Component Factor Analysis with Varimax Rotation of the BPRS scores at T0. Factor scores obtained were consequently computed as separate variables. Spearman non-parametric correlation analyses were performed between factor scores, amelioration in BPRS scores, and duration of hospitalization. 183 patients (140 M, 43 F) were included in the study. The mean age was 42.2 years±11.2 SD. The mean duration of hospitalization was 12 days±8.6. The BPRS scores showed a significant improvement at T1 compared to T0 (39.11±9.6 SD vs 54.89±13.8 SD, p < 0.0001). The factor analysis of BPRS scores at T0 extracted 4 Principal Factors: Depression/Anxiety, Resistance/Positive symptoms, Negative symptoms, and Activation. The Depression/Anxiety dimension was primarily determined by anxiety, depression, somatic concern and suicidal risk. The 49.2% of variance was explained by the factor analysis. The percentage of amelioration in BPRS scores was positively correlated to Depression/Anxiety score (r = 0.2; p < 0.005). Higher scores in the Depression/Anxiety dimension were related to a longer duration of hospitalization. Nevertheless, the percentage of amelioration measured by BPRS was not significantly related to the duration of hospitalization. As previous studies [2] showed, our research confirms that symptoms in Schizophrenia cluster together in distinct domains, one of which represented by Depression/Anxiety dimension. We found that patients with acute episode of schizophrenia presenting with a more relevant depressive component have a better outcome than the others. This fact could be due to a greater awareness of illness and a worse subjective state that improve their compliance to therapeutic projects. The relationship between the presence of depression and longer duration of hospitalization could be explained by the fact that doctors perceive depressed patients as more needing in terms of cares than no-depressed ones.
P.3.a Psychotic disorders and antipsychotics – Psychotic disorders (clinical) References [1] Emsley, R.A, Oosthuizen, P.P., Joubert, A.F., Roberts, M.C., D.J. Stein, 1999 Depressive and anxiety symptoms in patients with schizophrenia and schizophreniform disorder. J Clin Psych 60, 747–751. [2] Ventura, J, Nuechterlein, K.H., Subotnik, K.L., Gutkind, D., Gilbert, E.A. 2000 Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale. Psych Res 97, 129–135
P.3.a.017 Decreased serum proBDNF/BDNF ratio in patients with schizophrenia
S395
ratio was found in patients with schizophrenia in comparison with healthy controls (p < 0.05). Conclusions: Firstly, this study demonstrated that proBDNF can be measured in human serum and that the proBDNF/BDNF ratio is altered in patients with schizophrenia. We hypothesized that abnormal proteolitic processes occurring in schizophrenia brains may lead to decreased proBDNF/BDNF ratio, thus affecting neuronal plasticity. We will further explore whether proBDNF/BDNF ratio correlates with cognitive performances; also, we will investigate the effect of antipsychotics (typicals vs atypicals) on the serum proBDNF/BDNF ratio in patients with schizophrenia. References
D. Carlino1 ° , E. Leone2 , E. Tongiorgi2 , M. De Vanna1 . 1 Psychiatric Clinic University of Trieste, Department of Clinical Morphological and Technological Sciences, Trieste, Italy; 2 B.R.A.I.N. Centre for Neuroscience University of Trieste, Department of Biology, Trieste, Italy Objectives: Brain Derived Neurotrophic Factor (BDNF), a member of the family of neurotrophins (NTs), is central to many facets of CNS function, from differentiation and neuronal survival to synaptogenesis and activity-dependent forms of synaptic plasticity. Several studies demonstrated that abnormal BDNF levels are involved in the pathophysiology of schizophrenia. Conversely, there are no studies investigating the role of BDNF’s precursor (proBDNF) in this disorder. Indeed, proBDNF as well as the other pro-NTs is crucial in signalling pathways by interacting with the p75 neurotrophin receptor (p75NTR). Interestingly, proneurotrophins seem to have biological effects that oppose those of mature neurotrophins, promoting apoptosis and Long Term Depression (LTD). Therefore, the proteolytic cleavage of proneurotrophins could represent a mechanism that controls the direction of action of neurotrophins and the altered balance of these two forms may determine abnormal brain functions. Based on this evidence, we measured by western blot proBDNF/BDNF ratio in human serum. Then we compared this ratio in patients with schizophrenia and healthy controls. Methods: 40 patients with a DSM-IV-TR diagnosis of schizophrenia and 40 aged and gender matched healthy volunteers were investigated. For serum samples preparation, blood (5 ml) was collected in anticoagulant-free tubes and maintained at room temperature for 1 hour, followed by 1 hour at 4ºC to allow complete release of Brain Derived Neurotrophic Factor from platelets. Finally, serum was isolated by centrifugation at 2000 g for 10 min at 4ºC. Total serum Brain Derived Neurotrophic Factor (ng/mL) was measured by using a specific ELISA kit (BDNF Emax imuunoassay system, Promega Co, USA). Subsequently western blot was used to detect both mature and precursor form of Brain Derived Neurotrophic Factor using a specific antiBDNF antibody (N-20 Santa Cruz, USA). The antibody specificity, previously demonstrated in human brain, was ensured in human serum by competitive Western blot. Relative amounts of proBDNF/BDNF ratio in schizophrenic patients and healthy volunteers were determined by densitometry of the immunoreactive bands. The Sigma Stat 3.1 Software was used for all statistical analysis. A two tailed statistical significance was set at p < 0.05. A One-way ANOVA was conducted to detect the between group differences in total serum Brain Derived Neurotrophic Factor and proBDNF/BDNF. Results: There were no statistically significant differences between patients with schizophrenia and healthy controls (p = 0.558) in terms of total serum Brain Derived Neurotrophic Factor. On the contrary, a significant reduction of serum proBDNF/BDNF
[1] Woo, N.H., Teng, H.K., Siao, C.J., Chiaruttini, C., Pang, P.T., Milner, T.A., Hempstead, B.L., Lu, B., 2005, Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci 8, 1069–1077. [2] Shimizu, E., Hashimoto, K., Watanabe, H., Komatsu, N., Okamura, N., Koike, K., Shinoda, N., Nakazato, M., Kumakiri, C., Okada, S., Iyo M., 2003, Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls. Neurosci. Lett. 351, 111–114. [3] Volosin, M., Song, W., Almeida, R.D., Kaplan, D.R., Hempstead, B.L., Friedman, W.J., 2006, Interaction of survival and death signaling in basal forebrain neurons: roles of neurotrophins and proneurotrophins. J Neurosci 19, 7756–7766.
P.3.a.018 Changes in antisaccadic test, gain and negative symptoms in schizophrenic patients treated with glycine D. Strzelecki1 ° , J. Rabe-Jablonska1 . 1 Medical University of Lodz, Department of Affective and Psychotic Disorders, Lodz, Poland Purpose of the study: Glutamatergic NMDA (N-methyl-Daspartate) receptor plays an important role in cognitive processes as visuo-spatial attention and visuo-motor skills and also participate as a glutamatergic ionotropic receptor in mechanisms of control of other neurotransmitter systems as e.g. dopaminergic, adrenergic or serotoninergic system. Glycine – simple aminoacid, is a natural coagonist of NMDA receptor necessary in its proper and effective functioning. According to hypoNMDA hypothesis treatment with high doses of glycine (max. 60g per day per os) can increase function of NMDA receptor and improve primary negative symptoms in schizophrenia and also normalize eye movements, which are commonly disturbed in majority of schizophrenic patients and their families. The work objective was evaluation of glycine influence on eye movements in schizophrenia as an augmentation of antipsychotic treatment with typical or/and atypical drugs. Methods: Twenty eight patients with predominant negative symptoms (mean 25.7 points in PANSS Negative symptom subscale) in stable clinical condition and stable antipsychotic medication for min. 3 months, had completed 6 weeks, prospective, open label study (Thirty two patients was enrolled). Between visits 1 and 2 (weeks 0 and 6) patients received solution of glycine in high oral doses (0.8 g/kg/day/2 doses) with previous typical or/and atypical antipsychotic treatment. On both visits glycine influence on eye movements was assessed based on: 1) Eye tracking (gain in 3 velocities of object: 29, 38 and 49º/s), 2) Saccadic task (latency, time of saccade) and 3) Antisaccadic task (number of errors in task). Additionally we rated intensity of schizophrenic symptoms using PANSS.