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193. Emitted P3a and P3b in Chronic Schizophrenia and in First-Episode Schizophrenia-Spectrum Psychosis
Biological Psychiatry
Thursday Abstracts
Day-3PM and effects on cognitive outcomes including visuospatial working-memory (VSWM) and verbal memory were evaluated. Results: At baseline, controls performed better on several cognitive outcomes than SZ (p,0.001). Patients appeared to perform better on 1mg/day in contrast to controls on 2mg/day. Correlation analyses between plasma varenicline levels and VSWM performance revealed improved VSWM performance with increased plasma levels among SZ patients in 1mg/day condition (p,0.08). For controls, plasma levels were positively related to VSWM (p50.013) and verbal memory (p50.005) performance in the 2mg/day condition. There were no significant effects of varenicline on psychotic or depressive symptoms. Conclusions: Patients on 1mg/day condition and controls on 2mg/day condition had better cognitive performance with increasing plasma levels. Larger studies with longer duration of varenicline treatment are warranted to parse the relationships between varenicline, plasma levels and cognition in non-smokers with SZ. Supported By: Institute of Medical Sciences Graduate Fellowship from the University of Toronto; Investigatorinitiated grant from Pfizer, Inc. (WI171136); CIHR Operating Grant MOP115145 (to Dr. George). Keywords: Schizophrenia, Non-Smokers, Varenicline, Cognition, Visuospatial Working Memory
193. Emitted P3a and P3b in Chronic Schizophrenia and in First-Episode Schizophrenia-Spectrum Psychosis Alexis G McCathern, Brian A Coffman, Timothy K Murphy, Kayla L Ward, Sarah Haigh, and Dean Salisbury University of Pittsburgh School of Medicine Background: The P3 is biphasic, with P3a reflecting automatic orienting and P3b cognitive processing. Reductions in P3b in first episode schizophrenia-spectrum individuals (FE) are present on target detection “oddball” tasks, although P3a reductions are equivocal. P3 can also be “emitted” by an expected but missing stimulus. Surprisingly, the emitted P3 has been little studied in longterm schizophrenia (Sz) and not at all in FE. Methods: Twenty-seven Sz (minimum 5 years diagnosis) were compared to 20 matched controls (HCSz), and 27 FE (within 6 months of their first psychotic episode) were compared to 26 matched controls (HCFE). Participants were presented with standard sets of four identical tones (1kHz, 50ms, 330ms SOA, 750ms ITI). For one in seven sets, the fourth tone was missing. Participants counted the number of tones within each set, with no instruction to detect missing tones. Results: The P3b emitted by missing tones was significantly reduced in both Sz and FE (p5.039 and p5.017, respectively). Conclusions: Sz and FE displayed impaired emitted P3b on a missing tone task. Presumably, HC implicitly developed an expectation for groups of 4 tones, with the P3b emitted when the 4th tone was missing. By contrast, Sz and FE did not. The
S80
emitted P3b may be useful to understand cognitive neuropathophysiology early in psychosis. Its reduction in FE suggests it may show promise as a biomarker of schizophrenia presence. Future work will assess its sensitivity to the schizophrenia prodrome prior to conversion to frank psychosis among clinical high risk individuals. Supported By: NIH R01 MH094328 Keywords: First-Episode Psychosis (FEP), Schizophrenia, P300
194. Exploring Neural Basis of Emotional Cognition Using Fear Conditioning by Interpersonal Conflicts in Patients with Schizophrenia Hideaki Tani1, Mitsuhiro Tada2, Takefumi Suzuki3, Masaru Mimura1, and Hiroyuki Uchida1 1
Department of Neuropsychiatry, Keio University School of Medicine, 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Saiseikai Central Hospital, 3Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Inokashira Hospital Background: Emotional cognition has been an important area of research in schizophrenia. Simple aversive stimuli conventionally used in previous conditioning paradigm such as electric shock have a weakness of not representing real-world conflicts that seriously involve social context. We recently developed an interpersonal stimulus to reflect such a social context, and it has successfully been applied to healthy individuals (Tada et al. Plos One, 2015). The objective of this study was to explore neural basis of emotional cognition in schizophrenia by measuring autonomic response using skin conductance response (SCR) to the interpersonal stimuli. Methods: Eighteen female patients with schizophrenia (ICD-10) underwent two types of fear conditioning experiments of an aversive sound, and an interpersonal stimulus with a picture of actors’ faces with recorded unpleasant verbal messages. The paradigm consisted of three consecutive phases: habituation, acquisition, and extinction. Conditioned response was quantified by differential SCR between stimuli paired with (CS1) and unpaired with (CS-) unconditioned stimuli (US) using paired ttests during the acquisition, early and late extinction phases. Results: Fourteen subjects with evaluable SCRs to the CS1 during the acquisition phase to either of two stimuli were included in the analysis. No statistically significant differences in SCRs were observed between CS1 and CS- in both acquisition and extinction phases, regardless of the types of stimuli. Conclusions: Female patients with schizophrenia failed to get conditioned with the interpersonal stimuli or the aversive sound, which suggests their qualitative difference in emotional processing from healthy individuals. Supported By: Inokashira Hospital Grants for Psychiatry Research; Lilly Grant Keywords: emotional cognition, fear conditioning, interpersonal conflicts, skin conductance, schizophrenia
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
Thursday Abstracts
Day-3PM and effects on cognitive outcomes including visuospatial working-memory (VSWM) and verbal memory were evaluated. Results: At baseline, controls performed better on several cognitive outcomes than SZ (p,0.001). Patients appeared to perform better on 1mg/day in contrast to controls on 2mg/day. Correlation analyses between plasma varenicline levels and VSWM performance revealed improved VSWM performance with increased plasma levels among SZ patients in 1mg/day condition (p,0.08). For controls, plasma levels were positively related to VSWM (p50.013) and verbal memory (p50.005) performance in the 2mg/day condition. There were no significant effects of varenicline on psychotic or depressive symptoms. Conclusions: Patients on 1mg/day condition and controls on 2mg/day condition had better cognitive performance with increasing plasma levels. Larger studies with longer duration of varenicline treatment are warranted to parse the relationships between varenicline, plasma levels and cognition in non-smokers with SZ. Supported By: Institute of Medical Sciences Graduate Fellowship from the University of Toronto; Investigatorinitiated grant from Pfizer, Inc. (WI171136); CIHR Operating Grant MOP115145 (to Dr. George). Keywords: Schizophrenia, Non-Smokers, Varenicline, Cognition, Visuospatial Working Memory
193. Emitted P3a and P3b in Chronic Schizophrenia and in First-Episode Schizophrenia-Spectrum Psychosis Alexis G McCathern, Brian A Coffman, Timothy K Murphy, Kayla L Ward, Sarah Haigh, and Dean Salisbury University of Pittsburgh School of Medicine Background: The P3 is biphasic, with P3a reflecting automatic orienting and P3b cognitive processing. Reductions in P3b in first episode schizophrenia-spectrum individuals (FE) are present on target detection “oddball” tasks, although P3a reductions are equivocal. P3 can also be “emitted” by an expected but missing stimulus. Surprisingly, the emitted P3 has been little studied in longterm schizophrenia (Sz) and not at all in FE. Methods: Twenty-seven Sz (minimum 5 years diagnosis) were compared to 20 matched controls (HCSz), and 27 FE (within 6 months of their first psychotic episode) were compared to 26 matched controls (HCFE). Participants were presented with standard sets of four identical tones (1kHz, 50ms, 330ms SOA, 750ms ITI). For one in seven sets, the fourth tone was missing. Participants counted the number of tones within each set, with no instruction to detect missing tones. Results: The P3b emitted by missing tones was significantly reduced in both Sz and FE (p5.039 and p5.017, respectively). Conclusions: Sz and FE displayed impaired emitted P3b on a missing tone task. Presumably, HC implicitly developed an expectation for groups of 4 tones, with the P3b emitted when the 4th tone was missing. By contrast, Sz and FE did not. The
S80
emitted P3b may be useful to understand cognitive neuropathophysiology early in psychosis. Its reduction in FE suggests it may show promise as a biomarker of schizophrenia presence. Future work will assess its sensitivity to the schizophrenia prodrome prior to conversion to frank psychosis among clinical high risk individuals. Supported By: NIH R01 MH094328 Keywords: First-Episode Psychosis (FEP), Schizophrenia, P300
194. Exploring Neural Basis of Emotional Cognition Using Fear Conditioning by Interpersonal Conflicts in Patients with Schizophrenia Hideaki Tani1, Mitsuhiro Tada2, Takefumi Suzuki3, Masaru Mimura1, and Hiroyuki Uchida1 1
Department of Neuropsychiatry, Keio University School of Medicine, 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Saiseikai Central Hospital, 3Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, Inokashira Hospital Background: Emotional cognition has been an important area of research in schizophrenia. Simple aversive stimuli conventionally used in previous conditioning paradigm such as electric shock have a weakness of not representing real-world conflicts that seriously involve social context. We recently developed an interpersonal stimulus to reflect such a social context, and it has successfully been applied to healthy individuals (Tada et al. Plos One, 2015). The objective of this study was to explore neural basis of emotional cognition in schizophrenia by measuring autonomic response using skin conductance response (SCR) to the interpersonal stimuli. Methods: Eighteen female patients with schizophrenia (ICD-10) underwent two types of fear conditioning experiments of an aversive sound, and an interpersonal stimulus with a picture of actors’ faces with recorded unpleasant verbal messages. The paradigm consisted of three consecutive phases: habituation, acquisition, and extinction. Conditioned response was quantified by differential SCR between stimuli paired with (CS1) and unpaired with (CS-) unconditioned stimuli (US) using paired ttests during the acquisition, early and late extinction phases. Results: Fourteen subjects with evaluable SCRs to the CS1 during the acquisition phase to either of two stimuli were included in the analysis. No statistically significant differences in SCRs were observed between CS1 and CS- in both acquisition and extinction phases, regardless of the types of stimuli. Conclusions: Female patients with schizophrenia failed to get conditioned with the interpersonal stimuli or the aversive sound, which suggests their qualitative difference in emotional processing from healthy individuals. Supported By: Inokashira Hospital Grants for Psychiatry Research; Lilly Grant Keywords: emotional cognition, fear conditioning, interpersonal conflicts, skin conductance, schizophrenia
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal