- Email: [email protected]
354. Negative Symptoms and Cognitive Deficits Predict Different Elements of Everyday Functioning in People with Schizophrenia
Biological Psychiatry
Friday Abstracts
Conclusions: The availability of data from large trials of interventions for negative symptoms can be used to improve the design of future trials. Keywords: Schizophrenia, Negative Symptoms
353. New Negative Symptom Assessment Tools for Clinical Trials William Horan1, Felice Reddy2, and Michael Green2 1
Semel Institute for Neuroscience & Human Behavior at UCLA, 2UCLA Background: There has been a recent surge of interest in developing novel treatments for the debilitating negative symptoms of schizophrenia. In this context, considerable attention has focused on developing new assessment tools for clinical trials that are grounded in contemporary clinical and affective neuroscience research, including interview- and performance-based approaches. Methods: The psychometric properties and validity of two new interviews, the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS), have been examined in several studies. To address potential challenges associated with interviewbased assessment, our team has also evaluated the suitability of conceptually related measures of reward processing for use in clinical trials in 130 outpatients and 70 healthy controls. Results: The CAINS and BNSS both assess the primary experiential and expression-related subdomains of negative symptoms. Their psychometrics and validity (e.g., r’s . .40 between CAINS and community functioning) are generally comparable and strong, though their specific content and rating approaches differ. We have found that some effortbased decision making, probabilistic reward learning, and delay discounting measures show promising characteristics (e.g., large patient-control differences, test-retest correlations . .70) for clinical trial endpoints. However, these performance measures show generally small, non-significant relations to interview measures. Conclusions: A new generation of clinical interview-based measures is now in widespread use internationally. We find generally small relations between interview and performance measures, and the research literature in this area is remarkably mixed. The inconsistent convergence between these approaches raises fundamental questions about the optimal assessment of negative symptoms. Supported By: RO1; VA Merit Keywords: Schizophrenia, Negative Symptoms, reward processing
354. Negative Symptoms and Cognitive Deficits Predict Different Elements of Everyday Functioning in People with Schizophrenia Philip Harvey University of Miami Background: The overlap between negative symptoms and cognitive deficits is unclear: some definitions of negative
symptoms include cognitive or functional deficits as features. Studies of the relationship between negative and cognitive symptoms and impairments in everyday outcomes often lack precision. We address this issue in a large sample of people with schizophrenia examined with common assessments. We hypothesized that negative symptoms would predict social outcomes, but not other outcomes and that cognition would not predict social functioning. Methods: Patients with schizophrenia (n51035) participated in this study. They were rated by clinician informants for their everyday functioning, tested with assessments of cognition and functional capacity, and examined with the PANSS. We tested the hypotheses with confirmatory factor analysis, using a comparison model that specified that negative symptoms, cognition, and functional capacity had equivalent influences on all aspects of outcome. In testing the hypothetical model, we fixed the correlations between negative symptoms and vocational and everyday activities to 0, similarly fixing the correlation between cognition and social outcomes to 0. Results: The overall model had a suitable fit: RMSEA 5 .049, CFI 5 .962. Using sequential chi-square subtraction, the difference in model fit between the hypothetical and comparison models was statistically significant: Chi-square 548.8, p5.0001, indicating that the hypothetical model had a significantly better fit. Conclusions: Our analyses supported the idea that negative and cognitive symptoms had different correlations with different aspects of functional outcomes. These data support separate treatments for negative symptoms and cognition to improve functional outcomes in people with schizophrenia. Supported By: NIMH RO1 63116; 78775; 93432 Keywords: Negative Symptoms, Neurocognition, functional capacity, Everyday functioning
355. Efficacy and Safety of MIN-101: A Drug for the Treatment of Negative Symptoms in Schizophrenia Michael Davidson Self-Employed Background: To compare the efficacy, safety, and tolerability of MIN-101, a compound with affinities for sigma 2 and 5HT2A receptors, to placebo in treating negative symptoms, in patients with stable symptoms of schizophrenia. Methods: This trial enrolled 244 patients with schizophrenia who were symptomatically stable for $ 3 months prior to entering the trial and had baseline scores $ 20 on the 3factors negative subscale of the PANSS. Patients were randomized to daily monotherapy with MIN 101 32 mg, MIN101 64 mg, or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the 5-factors (pentagonal) model. Results: Statistically significant and dose dependent reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (p # 0.022; effect size (ES) 0.45 .and # 0.003; ES 0.58, respectively). The validity of effects on the primary endpoint was supported by similar effects on most of the secondary measurements including: PANSS 3-factors negative symptoms subscale, PANSS total
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S145
Friday Abstracts
Conclusions: The availability of data from large trials of interventions for negative symptoms can be used to improve the design of future trials. Keywords: Schizophrenia, Negative Symptoms
353. New Negative Symptom Assessment Tools for Clinical Trials William Horan1, Felice Reddy2, and Michael Green2 1
Semel Institute for Neuroscience & Human Behavior at UCLA, 2UCLA Background: There has been a recent surge of interest in developing novel treatments for the debilitating negative symptoms of schizophrenia. In this context, considerable attention has focused on developing new assessment tools for clinical trials that are grounded in contemporary clinical and affective neuroscience research, including interview- and performance-based approaches. Methods: The psychometric properties and validity of two new interviews, the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS), have been examined in several studies. To address potential challenges associated with interviewbased assessment, our team has also evaluated the suitability of conceptually related measures of reward processing for use in clinical trials in 130 outpatients and 70 healthy controls. Results: The CAINS and BNSS both assess the primary experiential and expression-related subdomains of negative symptoms. Their psychometrics and validity (e.g., r’s . .40 between CAINS and community functioning) are generally comparable and strong, though their specific content and rating approaches differ. We have found that some effortbased decision making, probabilistic reward learning, and delay discounting measures show promising characteristics (e.g., large patient-control differences, test-retest correlations . .70) for clinical trial endpoints. However, these performance measures show generally small, non-significant relations to interview measures. Conclusions: A new generation of clinical interview-based measures is now in widespread use internationally. We find generally small relations between interview and performance measures, and the research literature in this area is remarkably mixed. The inconsistent convergence between these approaches raises fundamental questions about the optimal assessment of negative symptoms. Supported By: RO1; VA Merit Keywords: Schizophrenia, Negative Symptoms, reward processing
354. Negative Symptoms and Cognitive Deficits Predict Different Elements of Everyday Functioning in People with Schizophrenia Philip Harvey University of Miami Background: The overlap between negative symptoms and cognitive deficits is unclear: some definitions of negative
symptoms include cognitive or functional deficits as features. Studies of the relationship between negative and cognitive symptoms and impairments in everyday outcomes often lack precision. We address this issue in a large sample of people with schizophrenia examined with common assessments. We hypothesized that negative symptoms would predict social outcomes, but not other outcomes and that cognition would not predict social functioning. Methods: Patients with schizophrenia (n51035) participated in this study. They were rated by clinician informants for their everyday functioning, tested with assessments of cognition and functional capacity, and examined with the PANSS. We tested the hypotheses with confirmatory factor analysis, using a comparison model that specified that negative symptoms, cognition, and functional capacity had equivalent influences on all aspects of outcome. In testing the hypothetical model, we fixed the correlations between negative symptoms and vocational and everyday activities to 0, similarly fixing the correlation between cognition and social outcomes to 0. Results: The overall model had a suitable fit: RMSEA 5 .049, CFI 5 .962. Using sequential chi-square subtraction, the difference in model fit between the hypothetical and comparison models was statistically significant: Chi-square 548.8, p5.0001, indicating that the hypothetical model had a significantly better fit. Conclusions: Our analyses supported the idea that negative and cognitive symptoms had different correlations with different aspects of functional outcomes. These data support separate treatments for negative symptoms and cognition to improve functional outcomes in people with schizophrenia. Supported By: NIMH RO1 63116; 78775; 93432 Keywords: Negative Symptoms, Neurocognition, functional capacity, Everyday functioning
355. Efficacy and Safety of MIN-101: A Drug for the Treatment of Negative Symptoms in Schizophrenia Michael Davidson Self-Employed Background: To compare the efficacy, safety, and tolerability of MIN-101, a compound with affinities for sigma 2 and 5HT2A receptors, to placebo in treating negative symptoms, in patients with stable symptoms of schizophrenia. Methods: This trial enrolled 244 patients with schizophrenia who were symptomatically stable for $ 3 months prior to entering the trial and had baseline scores $ 20 on the 3factors negative subscale of the PANSS. Patients were randomized to daily monotherapy with MIN 101 32 mg, MIN101 64 mg, or placebo in a 1:1:1 ratio. The primary endpoint was the PANSS negative symptom score based on the 5-factors (pentagonal) model. Results: Statistically significant and dose dependent reduction in the primary endpoint score was demonstrated for MIN-101 32 mg and 64 mg compared to placebo (p # 0.022; effect size (ES) 0.45 .and # 0.003; ES 0.58, respectively). The validity of effects on the primary endpoint was supported by similar effects on most of the secondary measurements including: PANSS 3-factors negative symptoms subscale, PANSS total
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S145