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Poster #T211 GLUTAMATERGIC DYSFUNCTION ASSOCIATED WITH FOCAL BRAIN CORTICAL THICKNESS IN ANTIPSYCHOTIC-NAÏVE PATIENTS WITH SCHIZOPHRENIA
S364
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
Poster #T210 PALIPERIDONE PALMITATE IN ACUTE PATIENTS WITH SCHIZOPHRENIA – TREATMENT RESPONSE, SAFETY AND TOLERABILITY: A PROSPECTIVE FLEXIBLE DOSE STUDY IN PATIENTS PREVIOUSLY UNSUCCESSFULLY TREATED WITH ORAL ANTIPSYCHOTICS Andreas Schreiner 1,2 , Paul Bergmans 3 , Pierre Cherubin 4 , Elmars Rancans 5 , Yasin Bez 6 , Eduardo Parellada 7 , Bernado Carpiniello 8 , Pierre Vidailhet 9 , Ludger Hargarter 10,2 1 EMEA; 2 Medical Affairs; 3 Janssen-Cilag Benelux; 4 Janssen Cilag France; 5 Riga Stradins University, Latvia; 6 Dicle University Medical Faculty, Turkey; 7 Hospital Clinic de Barcelona, Spain; 8 Clinica Psichiatrica Università di Cagliari, Italy; 9 Centre Hospitalier Régional Universitaire de Strasbourg, France; 10 Janssen-Cilag Germany Background: Exploring treatment outcomes with once-monthly paliperidone palmitate (PP) in more representative patients with schizophrenia may guide recommendations for use of and transition to PP. This study explores tolerability, safety and treatment response of flexible doses of PP in adult patients with an acute exacerbation of schizophrenia previously unsuccessfully treated with oral antipsychotics. Methods: International prospective 6-month, open-label study. Outcome parameters were change in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), adverse events (AEs), and weight change. Results: 212 acute patients (ITT, intent-to-treat population): 59.0% male, mean age 36.4±12.1 years, 85.4% paranoid schizophrenia were enrolled. Main reason for transition from prior oral antipsychotic treatment was lack of efficacy in 45.8% of patients. 70.3% of patients completed the 6-month study. Most frequent reasons for early discontinuation were subject choice (9.4%), AE (9.0%), loss to follow-up (4.7%) and lack of efficacy (2.8%). Recommended initiation regimen of PP (150 mg eq on day 1 and 100 mg eq on day 8) was administered in 92.9% of subjects. Mean baseline PANSS total score decreased from 98.5±20.1 as of day 8 of treatment to 67.4±24.0 at endpoint (mean change -31.0±28.97; 95% confidence interval [CI] −35.0; −27.1; p<0.0001). 66.7% of patients improved ≥30% in PANSS total score and percentage of patients rated markedly ill or worse in CGI-S decreased from 75.1% at baseline to 20.5% at endpoint. AEs reported in ≥5% were injection site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache (6.1%) and anxiety (6.1%). Mean weight change at endpoint was 2.6±5.6 kg (95%CI 1.8; 3.4). Discussion: These data support results from previous randomized controlled studies that flexibly dosed paliperidone palmitate is well tolerated and associated with an early and clinically relevant treatment response in acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics.
Poster #T211 GLUTAMATERGIC DYSFUNCTION ASSOCIATED WITH FOCAL BRAIN CORTICAL THICKNESS IN ANTIPSYCHOTIC-NAÏVE PATIENTS WITH SCHIZOPHRENIA Carl C. Schultz 1 , Alexander Gussew 2 , Igor Nenadic 3 , Natalie Biesel 3 , Christian Gaser 4 , Bianca Besteher 5 , Jürgen Reichenbach 6 , Heinrich Sauer 1 , Stefan Smesny 1,3 1 Jena University Hospital, Department of Psychiatry and Psychotherapy; 2 Department of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany; 3 Jena University Hospital; 4 Structural Brain Mapping Group, Department of Neurology, Jena University Hospital; 5 Department of Psychiatry and Psychotherapy, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany; 6 Medical Physics Group, Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Jena, Germany Background: Altered prefrontal glutamatergic neurotransmission is of critical relevance for major aspects of the so called “hypofrontality” and associated negative symptoms and cognitive deficits. Hence, exploring the interrelation between disturbed prefrontal glutamatergic neurotransmission and focal brain structural abnormalities might further elucidate the neuronal foundations of altered prefrontal circuitry in schizophrenia. In this multimodal study, we thus focused on associations between dorsolateral
prefrontal glutamate metabolism and cortical structure in first episode antipsychotic-naïve schizophrenia patients. Methods: Dorsolateral prefrontal cortex (DLPFC) glutamate was measured by proton MR spectroscopy (1H-MRS). Cortical thickness was computed with an automated surface based technique (FreeSurfer). 28 antipsychoticnaïve first episode patients and 27 matched healthy controls were integrated in this study. DLPFC glutamate values were correlated with node-by-node cortical thickness covering the entire cortex in patients and controls. Results: Patients demonstrated significantly reduced DLPFC glutamate levels and cortical thinning in prefrontal and temporal regions. In patients, decreased DLPFC glutamate was associated with reduced cortical thickness in the DLPFC and the dorsal anterior cingulate cortex (dACC). This association was not observed in healthy controls with a significant difference at a whole brain level. Discussion: In conclusion, we provide first evidence for a direct linkage of prefrontal glutamatergic dysregulation and cortical thinning in early acute schizophrenia observed in neuroanatomical key regions including the DLPFC and the dACC. This co-occurrence of prefrontal glutamatergic hypofunction and cortical abnormalities may be a correlate of focally disturbed neuronal/synaptic plasticity in the early course of schizophrenia. Reference: [1] Schultz, CC. et al., submitted.
Poster #T212 MENTAL HEALTH LITERACY ON PSYCHOSIS AND DEPRESSION: DO LABELING AND CAUSAL ATTRIBUTION AFFECT TREATMENT RECOMMENDATIONS? Frauke Schultze-Lutter, Chantal Michel, Benno G. Schimmelmann University Hospital of Child and Adolescent Psychiatry and Psychotherapy Bern, University of Bern Background: Good mental health literacy is thought to improve helpseeking and treatment compliance. Therefore, we investigated the treatment recommendations for psychosis and depression in a general population sample in relation to the recognition and causal attribution. Methods: 1’184 German-speaking participants of a telephone survey (age 16 to 40) were asked to answer a questionnaire on mental health literacy and attitudes whose two versions vary in their diagnostically unlabeled case vignette (schizophrenia or depression). 1’061 (89.6%) agreed to participate, 645 (60.8%) questionnaires were returned: 331 with a schizophrenia case vignette, 314 with a depression case vignette. Results: Type of the vignette had a near moderate effect on the main treatment recommendation that could be chosen from 7 categories: Psychotherapy received the highest degree of recommendation throughout – though even slightly more for the schizophrenia vignette (Cramer’s V=0.165), while “electro-convulsive therapy” (ECT) was hardly ever recommended for both vignettes. At a moderate effect size (Cramer’s V=0. 292), the type of the depicted mental problem had the largest effect on the recommendation of a psychopharmacological treatment: it was recommended for psychosis by 68.9%, and for depression by just 39.8% of the respective vignette responders. Thus, for the depression vignette, all treatment options but ECT were more frequently recommended than medication. For the schizophrenia vignette, medication was the second most recommended treatment option. The effect of the type of vignette was even more pronounced when correct or incorrect labeling of the vignette was taken into account (Cramer’s V= 0.367 and 0.354): While correct labeling decreased the recommendation of both psychotherapy and alternative treatments in favor of medication in schizophrenia, it only decreased recommendation of alternative treatments in favor of medication in depression. Similar to the effect of correct labeling, the adoption of a biological or non-biological causal model had an additional, yet smaller increasing effect on the effect of the type of vignette (Cramer’s V= 0.320 and 0.195) that was similar in its direction. Discussion: In schizophrenia and severe depression, psychopharmacological treatment is considered indispensable by professionals, yet its acceptance in the young adult general population is very low. Surprisingly, the adoption of a biological causal model had only a limited positive effect on the recommendation of medication. The main positive effect on recommendation of medication was exerted by a correct recognition of the disorder. Other
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
Poster #T210 PALIPERIDONE PALMITATE IN ACUTE PATIENTS WITH SCHIZOPHRENIA – TREATMENT RESPONSE, SAFETY AND TOLERABILITY: A PROSPECTIVE FLEXIBLE DOSE STUDY IN PATIENTS PREVIOUSLY UNSUCCESSFULLY TREATED WITH ORAL ANTIPSYCHOTICS Andreas Schreiner 1,2 , Paul Bergmans 3 , Pierre Cherubin 4 , Elmars Rancans 5 , Yasin Bez 6 , Eduardo Parellada 7 , Bernado Carpiniello 8 , Pierre Vidailhet 9 , Ludger Hargarter 10,2 1 EMEA; 2 Medical Affairs; 3 Janssen-Cilag Benelux; 4 Janssen Cilag France; 5 Riga Stradins University, Latvia; 6 Dicle University Medical Faculty, Turkey; 7 Hospital Clinic de Barcelona, Spain; 8 Clinica Psichiatrica Università di Cagliari, Italy; 9 Centre Hospitalier Régional Universitaire de Strasbourg, France; 10 Janssen-Cilag Germany Background: Exploring treatment outcomes with once-monthly paliperidone palmitate (PP) in more representative patients with schizophrenia may guide recommendations for use of and transition to PP. This study explores tolerability, safety and treatment response of flexible doses of PP in adult patients with an acute exacerbation of schizophrenia previously unsuccessfully treated with oral antipsychotics. Methods: International prospective 6-month, open-label study. Outcome parameters were change in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), adverse events (AEs), and weight change. Results: 212 acute patients (ITT, intent-to-treat population): 59.0% male, mean age 36.4±12.1 years, 85.4% paranoid schizophrenia were enrolled. Main reason for transition from prior oral antipsychotic treatment was lack of efficacy in 45.8% of patients. 70.3% of patients completed the 6-month study. Most frequent reasons for early discontinuation were subject choice (9.4%), AE (9.0%), loss to follow-up (4.7%) and lack of efficacy (2.8%). Recommended initiation regimen of PP (150 mg eq on day 1 and 100 mg eq on day 8) was administered in 92.9% of subjects. Mean baseline PANSS total score decreased from 98.5±20.1 as of day 8 of treatment to 67.4±24.0 at endpoint (mean change -31.0±28.97; 95% confidence interval [CI] −35.0; −27.1; p<0.0001). 66.7% of patients improved ≥30% in PANSS total score and percentage of patients rated markedly ill or worse in CGI-S decreased from 75.1% at baseline to 20.5% at endpoint. AEs reported in ≥5% were injection site pain (13.7%), insomnia (10.8%), psychotic disorder (10.4%), headache (6.1%) and anxiety (6.1%). Mean weight change at endpoint was 2.6±5.6 kg (95%CI 1.8; 3.4). Discussion: These data support results from previous randomized controlled studies that flexibly dosed paliperidone palmitate is well tolerated and associated with an early and clinically relevant treatment response in acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics.
Poster #T211 GLUTAMATERGIC DYSFUNCTION ASSOCIATED WITH FOCAL BRAIN CORTICAL THICKNESS IN ANTIPSYCHOTIC-NAÏVE PATIENTS WITH SCHIZOPHRENIA Carl C. Schultz 1 , Alexander Gussew 2 , Igor Nenadic 3 , Natalie Biesel 3 , Christian Gaser 4 , Bianca Besteher 5 , Jürgen Reichenbach 6 , Heinrich Sauer 1 , Stefan Smesny 1,3 1 Jena University Hospital, Department of Psychiatry and Psychotherapy; 2 Department of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany; 3 Jena University Hospital; 4 Structural Brain Mapping Group, Department of Neurology, Jena University Hospital; 5 Department of Psychiatry and Psychotherapy, Jena University Hospital, Friedrich-Schiller-University Jena, Jena, Germany; 6 Medical Physics Group, Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Jena, Germany Background: Altered prefrontal glutamatergic neurotransmission is of critical relevance for major aspects of the so called “hypofrontality” and associated negative symptoms and cognitive deficits. Hence, exploring the interrelation between disturbed prefrontal glutamatergic neurotransmission and focal brain structural abnormalities might further elucidate the neuronal foundations of altered prefrontal circuitry in schizophrenia. In this multimodal study, we thus focused on associations between dorsolateral
prefrontal glutamate metabolism and cortical structure in first episode antipsychotic-naïve schizophrenia patients. Methods: Dorsolateral prefrontal cortex (DLPFC) glutamate was measured by proton MR spectroscopy (1H-MRS). Cortical thickness was computed with an automated surface based technique (FreeSurfer). 28 antipsychoticnaïve first episode patients and 27 matched healthy controls were integrated in this study. DLPFC glutamate values were correlated with node-by-node cortical thickness covering the entire cortex in patients and controls. Results: Patients demonstrated significantly reduced DLPFC glutamate levels and cortical thinning in prefrontal and temporal regions. In patients, decreased DLPFC glutamate was associated with reduced cortical thickness in the DLPFC and the dorsal anterior cingulate cortex (dACC). This association was not observed in healthy controls with a significant difference at a whole brain level. Discussion: In conclusion, we provide first evidence for a direct linkage of prefrontal glutamatergic dysregulation and cortical thinning in early acute schizophrenia observed in neuroanatomical key regions including the DLPFC and the dACC. This co-occurrence of prefrontal glutamatergic hypofunction and cortical abnormalities may be a correlate of focally disturbed neuronal/synaptic plasticity in the early course of schizophrenia. Reference: [1] Schultz, CC. et al., submitted.
Poster #T212 MENTAL HEALTH LITERACY ON PSYCHOSIS AND DEPRESSION: DO LABELING AND CAUSAL ATTRIBUTION AFFECT TREATMENT RECOMMENDATIONS? Frauke Schultze-Lutter, Chantal Michel, Benno G. Schimmelmann University Hospital of Child and Adolescent Psychiatry and Psychotherapy Bern, University of Bern Background: Good mental health literacy is thought to improve helpseeking and treatment compliance. Therefore, we investigated the treatment recommendations for psychosis and depression in a general population sample in relation to the recognition and causal attribution. Methods: 1’184 German-speaking participants of a telephone survey (age 16 to 40) were asked to answer a questionnaire on mental health literacy and attitudes whose two versions vary in their diagnostically unlabeled case vignette (schizophrenia or depression). 1’061 (89.6%) agreed to participate, 645 (60.8%) questionnaires were returned: 331 with a schizophrenia case vignette, 314 with a depression case vignette. Results: Type of the vignette had a near moderate effect on the main treatment recommendation that could be chosen from 7 categories: Psychotherapy received the highest degree of recommendation throughout – though even slightly more for the schizophrenia vignette (Cramer’s V=0.165), while “electro-convulsive therapy” (ECT) was hardly ever recommended for both vignettes. At a moderate effect size (Cramer’s V=0. 292), the type of the depicted mental problem had the largest effect on the recommendation of a psychopharmacological treatment: it was recommended for psychosis by 68.9%, and for depression by just 39.8% of the respective vignette responders. Thus, for the depression vignette, all treatment options but ECT were more frequently recommended than medication. For the schizophrenia vignette, medication was the second most recommended treatment option. The effect of the type of vignette was even more pronounced when correct or incorrect labeling of the vignette was taken into account (Cramer’s V= 0.367 and 0.354): While correct labeling decreased the recommendation of both psychotherapy and alternative treatments in favor of medication in schizophrenia, it only decreased recommendation of alternative treatments in favor of medication in depression. Similar to the effect of correct labeling, the adoption of a biological or non-biological causal model had an additional, yet smaller increasing effect on the effect of the type of vignette (Cramer’s V= 0.320 and 0.195) that was similar in its direction. Discussion: In schizophrenia and severe depression, psychopharmacological treatment is considered indispensable by professionals, yet its acceptance in the young adult general population is very low. Surprisingly, the adoption of a biological causal model had only a limited positive effect on the recommendation of medication. The main positive effect on recommendation of medication was exerted by a correct recognition of the disorder. Other