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Poster #75 AGE EFFECTS ON P50 SUPPRESSION IN HEALTHY MALE VOLUNTEERS
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
needed to be included in the analysis (acute 6, remitted 2, UHR 0). The average number of diary entries completed over the seven days was high (acute: 28.5 (SD=7.7), remitted: 29.3 (SD=9.0), UHR: 30.9 (SD=6.4)). Regression analysis showed that total positive (β =-0.60, p=0.024), but not negative (β =-0.11, p=0.464), general (β =0.09, p=0.740) and CDS (β =0.28, p=0.110), symptom scores significantly predicted the number of diary entries completed across over the seven days. Diary scales generally showed moderate to strong correlations with PANSS and CDS interview scores (e.g. hallucinations, rho=0.66; paranoia, rho=0.64; anxiety,rho=0.67; depression, rho=0.32; hopelessness, rho=0.79), establishing convergent validity. Satisfactory testretest reliability was also demonstrated between odd-even time-points and the first and second half of the week. Two diary items were used to test reactivity to the methodology (analogue scale scored 1- not, 7 - very), which was minimal across all three groups (mean: 2.9 (SD: 2.2); mean: 2.9 (SD: 2.1)). Discussion: ClinTouch represents a feasible and valid way of assessing psychotic phenomena. In clinical settings it could be used to: generate discussion points for consultation; identify “relapse signatures”; highlight momentary symptom triggers; sensitively monitor treatment effects; or as an adjunct to psychosocial intervention. Further research is required to evaluate this procedure over longer assessment periods and when the software is uploaded onto patients own phones. Additionally, methods of increasing compliance to the method (e.g. games, item numbers) should be investigated.
Poster #74 CAN D2/3 BLOCKADE IMPROVE BASIC INFORMATION PROCESSING IN FIRST EPISODE SCHIZOPHRENIA? Signe W. Düring, Birte Glenthøj, Bob Oranje University of Copenhagen, Copenhagen, Denmark Background: Background Specific deficits in basic information processing, have long been thought to represent certain endophenotypes within the schizophrenia spectrum. These deficits can be reliably assessed using advanced electroencephalographical (EEG) paradigms. Deficits in sensory gating and selective attention are thought to contribute to both negative and positive symptoms in schizophrenia, by affecting perception and interpretation of the surroundings. Currently, only a few studies have been performed on the effects of selective dopamine D2/D3 antagonists on deficient sensory gating and selective attention of either antipsychotic naïve, or antipsychotic free, first-episode patients with schizophrenia. Methods: A minimum of 45 antipsychotic naïve, or antipsychotic free patients with first episode schizophrenia, and the same number of age and gender matched healthy controls, will be tested in the Copenhagen Psychophysiological Test Battery (CPTB) at baseline, and after a period of 4 weeks treatment with amisulpride. The antipsychotic free patients will have had less than two weeks of antipsychotic drug treatment at the time of inclusion. The CPTB paradigm uses auditory stimuli and advanced EEG to investigate psychophysiological parameters of sensory (P50 suppression) and sensorimotor gating (PPI, prepulse inhibition of the startle reflex), as well as selective attention (P300 amplitude, processing negativity and mismatch negativity). Results: Currently, 42 first episode patients have been tested at baseline, and 25 at FU. Recruitment is still in progress. Discussion: We hypothesize that patients, at the time of inclusion, will demonstrate reductions in PPI and P50 suppression, as well as reductions in P300 and processing negativity and mismatch negativity amplitudes compared to healthy controls. Following four weeks of treatment with amisulpride, we expect these deficiencies to have disappeared.
Poster #75 AGE EFFECTS ON P50 SUPPRESSION IN HEALTHY MALE VOLUNTEERS Mikkel Erlang 1,2,3 , Birte Glenthoj 1,2,3 , Bob Oranje 1,2,3 Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; 2 Center for Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; 3 University Psychiatric Center Glostrup, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark 1
Background: Cognitive disturbances, including attention deficits and sen-
sory gating, form core features in schizophrenia. P50 suppression which is thought to reflect pre-attentive sensory gating processes, have in a large number of studies and meta-analyses shown consistent deficits in P50 suppression in patients suffering from schizophrenia. P50 suppression has been shown to vary with age in a number of studies with focus on the agespan between early childhood and late adolescence. However, very few studies have reported age variation in the adult population, and the subject population of these clinical studies are relative small, age homogenous and prone to gender- and medication effects. The current study reports on the effect of age on P50 suppression as observed in large group of healthy males evenly distributed over a wide age span. Methods: Fifty-seven healthy male volunteers evenly distributed in age from 18-80 years, were tested in a P50 suppression paradigm. The paradigm consisted of 120 identical pared stimuli with an inter-stimulus interval of 500 ms and an inter trial interval of 10 s. The stimuli were all short pulses of white noise (1.4 ms and 80 dB). Both P50 latency and amplitude of the P50 waveform were measured at electrode Cz, for both conditioning (S1) and testing (S2) stimuli. Results: No age effect on P50 suppression (S2/S1) was found. We did however observe a significant effect of age on the subjects’ amplitudes to S1 stimuli and on their latency to S2 stimuli. Both these findings could be modelled as U shaped curves with a minimum around 45 years of age and maxima at 20 and 80 years of age. No significant effect of age was found on the subjects’ amplitudes to S2 stimuli nor on their latency to S1 stimuli although also these phenomena showed U-shaped curves with age, yet only at trend levels of significance. Discussion: In the current study we found age effects on latency and magnitude of the P50 waveform, but these findings did not have a significant impact on P50 suppression. The age related differences in magnitude seems to be similar enough at S1 and S2 to balance each other out in the ratio S2/S1, which is commonly used to express the level of P50 suppression. Our data therefore suggest that P50 suppression is stable over age, although its constituents (the responses to S1 and S2) are not. Future research should focus on effects of age on P50 suppression and its constituents in a longitudinal approach.
Poster #76 ACUTE KETAMINE INFUSION IN HEALTHY VOLUNTEERS: EFFECTS ON EARLY VISUAL PROCESSING Ivan G. Koychev 1 , Andrew Shepherd 1 , Wael El-Deredy 2 , Bill Deakin 1 , Corinna Haenschel 3 1 Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, United Kingdom; 2 School of Psychology, The University of Manchester, Manchester, United Kingdom; 3 Department of Psychology, City University, London, United Kingdom Background: Schizophrenia spectrum disorders are associated with cognitive abnormalities, such as working memory (WM) impairment and early sensory processing deficits, as demonstrated through electroencephalographic recordings. These information processing abnormalities are thought to be the result of a NMDA glutamate receptor abnormality. Ketamine, a non-competitive NMDA antagonist, can be used to explore the neurophysiological characteristics of acutely induced glutamate receptor dysfunction in healthy volunteers. In this study, we aimed to test whether the administration of IV ketamine can replicate the cognitive and electrophysiological patterns that our group previously observed in schizophrenia patients and schizotypal individuals. Methods: 44 healthy volunteers were randomised to receive either ketamine or placebo as IV infusion. The response to the infusion was measured using the Brief Psychiatric Rating Scale (BPRS) and the Clinician Administered Dissociative Symptom Scale (CADSS). A 64 channel electroencephalographic kit was used to obtain event-related potentials. 10 minutes after initiation of the infusion the participants completed a visual delayed discrimination task, where they were shown stimuli briefly (400 ms) and compared them to target cues presented after a 6 second delay period. The two groups were compared in respect to their performance on the WM task, the amplitude of the P1 and P300 event-related potentials (ERPs), as well as the signal power and phase-locking factor (PLF) of the evoked neural oscillations. Results: The BPRS and CADSS scores were significantly increased in the
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
needed to be included in the analysis (acute 6, remitted 2, UHR 0). The average number of diary entries completed over the seven days was high (acute: 28.5 (SD=7.7), remitted: 29.3 (SD=9.0), UHR: 30.9 (SD=6.4)). Regression analysis showed that total positive (β =-0.60, p=0.024), but not negative (β =-0.11, p=0.464), general (β =0.09, p=0.740) and CDS (β =0.28, p=0.110), symptom scores significantly predicted the number of diary entries completed across over the seven days. Diary scales generally showed moderate to strong correlations with PANSS and CDS interview scores (e.g. hallucinations, rho=0.66; paranoia, rho=0.64; anxiety,rho=0.67; depression, rho=0.32; hopelessness, rho=0.79), establishing convergent validity. Satisfactory testretest reliability was also demonstrated between odd-even time-points and the first and second half of the week. Two diary items were used to test reactivity to the methodology (analogue scale scored 1- not, 7 - very), which was minimal across all three groups (mean: 2.9 (SD: 2.2); mean: 2.9 (SD: 2.1)). Discussion: ClinTouch represents a feasible and valid way of assessing psychotic phenomena. In clinical settings it could be used to: generate discussion points for consultation; identify “relapse signatures”; highlight momentary symptom triggers; sensitively monitor treatment effects; or as an adjunct to psychosocial intervention. Further research is required to evaluate this procedure over longer assessment periods and when the software is uploaded onto patients own phones. Additionally, methods of increasing compliance to the method (e.g. games, item numbers) should be investigated.
Poster #74 CAN D2/3 BLOCKADE IMPROVE BASIC INFORMATION PROCESSING IN FIRST EPISODE SCHIZOPHRENIA? Signe W. Düring, Birte Glenthøj, Bob Oranje University of Copenhagen, Copenhagen, Denmark Background: Background Specific deficits in basic information processing, have long been thought to represent certain endophenotypes within the schizophrenia spectrum. These deficits can be reliably assessed using advanced electroencephalographical (EEG) paradigms. Deficits in sensory gating and selective attention are thought to contribute to both negative and positive symptoms in schizophrenia, by affecting perception and interpretation of the surroundings. Currently, only a few studies have been performed on the effects of selective dopamine D2/D3 antagonists on deficient sensory gating and selective attention of either antipsychotic naïve, or antipsychotic free, first-episode patients with schizophrenia. Methods: A minimum of 45 antipsychotic naïve, or antipsychotic free patients with first episode schizophrenia, and the same number of age and gender matched healthy controls, will be tested in the Copenhagen Psychophysiological Test Battery (CPTB) at baseline, and after a period of 4 weeks treatment with amisulpride. The antipsychotic free patients will have had less than two weeks of antipsychotic drug treatment at the time of inclusion. The CPTB paradigm uses auditory stimuli and advanced EEG to investigate psychophysiological parameters of sensory (P50 suppression) and sensorimotor gating (PPI, prepulse inhibition of the startle reflex), as well as selective attention (P300 amplitude, processing negativity and mismatch negativity). Results: Currently, 42 first episode patients have been tested at baseline, and 25 at FU. Recruitment is still in progress. Discussion: We hypothesize that patients, at the time of inclusion, will demonstrate reductions in PPI and P50 suppression, as well as reductions in P300 and processing negativity and mismatch negativity amplitudes compared to healthy controls. Following four weeks of treatment with amisulpride, we expect these deficiencies to have disappeared.
Poster #75 AGE EFFECTS ON P50 SUPPRESSION IN HEALTHY MALE VOLUNTEERS Mikkel Erlang 1,2,3 , Birte Glenthoj 1,2,3 , Bob Oranje 1,2,3 Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; 2 Center for Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; 3 University Psychiatric Center Glostrup, Faculty of Health Sciences, Copenhagen University, Copenhagen, Denmark 1
Background: Cognitive disturbances, including attention deficits and sen-
sory gating, form core features in schizophrenia. P50 suppression which is thought to reflect pre-attentive sensory gating processes, have in a large number of studies and meta-analyses shown consistent deficits in P50 suppression in patients suffering from schizophrenia. P50 suppression has been shown to vary with age in a number of studies with focus on the agespan between early childhood and late adolescence. However, very few studies have reported age variation in the adult population, and the subject population of these clinical studies are relative small, age homogenous and prone to gender- and medication effects. The current study reports on the effect of age on P50 suppression as observed in large group of healthy males evenly distributed over a wide age span. Methods: Fifty-seven healthy male volunteers evenly distributed in age from 18-80 years, were tested in a P50 suppression paradigm. The paradigm consisted of 120 identical pared stimuli with an inter-stimulus interval of 500 ms and an inter trial interval of 10 s. The stimuli were all short pulses of white noise (1.4 ms and 80 dB). Both P50 latency and amplitude of the P50 waveform were measured at electrode Cz, for both conditioning (S1) and testing (S2) stimuli. Results: No age effect on P50 suppression (S2/S1) was found. We did however observe a significant effect of age on the subjects’ amplitudes to S1 stimuli and on their latency to S2 stimuli. Both these findings could be modelled as U shaped curves with a minimum around 45 years of age and maxima at 20 and 80 years of age. No significant effect of age was found on the subjects’ amplitudes to S2 stimuli nor on their latency to S1 stimuli although also these phenomena showed U-shaped curves with age, yet only at trend levels of significance. Discussion: In the current study we found age effects on latency and magnitude of the P50 waveform, but these findings did not have a significant impact on P50 suppression. The age related differences in magnitude seems to be similar enough at S1 and S2 to balance each other out in the ratio S2/S1, which is commonly used to express the level of P50 suppression. Our data therefore suggest that P50 suppression is stable over age, although its constituents (the responses to S1 and S2) are not. Future research should focus on effects of age on P50 suppression and its constituents in a longitudinal approach.
Poster #76 ACUTE KETAMINE INFUSION IN HEALTHY VOLUNTEERS: EFFECTS ON EARLY VISUAL PROCESSING Ivan G. Koychev 1 , Andrew Shepherd 1 , Wael El-Deredy 2 , Bill Deakin 1 , Corinna Haenschel 3 1 Neuroscience and Psychiatry Unit, The University of Manchester, Manchester, United Kingdom; 2 School of Psychology, The University of Manchester, Manchester, United Kingdom; 3 Department of Psychology, City University, London, United Kingdom Background: Schizophrenia spectrum disorders are associated with cognitive abnormalities, such as working memory (WM) impairment and early sensory processing deficits, as demonstrated through electroencephalographic recordings. These information processing abnormalities are thought to be the result of a NMDA glutamate receptor abnormality. Ketamine, a non-competitive NMDA antagonist, can be used to explore the neurophysiological characteristics of acutely induced glutamate receptor dysfunction in healthy volunteers. In this study, we aimed to test whether the administration of IV ketamine can replicate the cognitive and electrophysiological patterns that our group previously observed in schizophrenia patients and schizotypal individuals. Methods: 44 healthy volunteers were randomised to receive either ketamine or placebo as IV infusion. The response to the infusion was measured using the Brief Psychiatric Rating Scale (BPRS) and the Clinician Administered Dissociative Symptom Scale (CADSS). A 64 channel electroencephalographic kit was used to obtain event-related potentials. 10 minutes after initiation of the infusion the participants completed a visual delayed discrimination task, where they were shown stimuli briefly (400 ms) and compared them to target cues presented after a 6 second delay period. The two groups were compared in respect to their performance on the WM task, the amplitude of the P1 and P300 event-related potentials (ERPs), as well as the signal power and phase-locking factor (PLF) of the evoked neural oscillations. Results: The BPRS and CADSS scores were significantly increased in the