- Email: [email protected]
Poster #137 THE PHRENIC COMPONENT OF ACUTE SCHIZOPHRENIA – A NAME AND ITS PHYSIOLOGICAL REALITY
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
tentions Hostility Questionnaire (AIHQ). Participants were requested to complete a Brüne’s Theory of Mind Picture Stories task and other emotional dysregulation scales including Rosenberg’s self-esteem, Beck depression inventory, Spielberg’s state and trait anxiety inventory. Results: As predicted, multiple regression analysis showed that in ambiguous situations, hostility bias score was found to be associated with theory of mind questionnaire score (adjusted R square=0.043, beta=-0.232, t=-2.22, p=0.029, tolerance > 0.9) and in intentional situations, hostility bias score to be associated with theory of mind skills (adjusted R square=0.087, beta=-0.236, t=-2.43, p=0.017, tolerance > 0.9), depression (adjusted R square=0.129, beta=0.359, t=3.45, p=0.001, tolerance > 0.8) and self-esteem (adjusted R square=0.214, beta=0.333, t=3.20, p=0.002, tolerance > 0.8). Also blaming indexes in ambiguous and intentional situations were related with self-esteem (adjusted R square=0.067, beta=-0.278, t=-2.69, p=0.009, tolerance > 0.7) and depression (adjusted R square=0.040, beta=0.226, t=2.15, p=0.034, tolerance > 0.9) in respect. Discussion: Hostility bias in ambiguous and intentional social contexts may be associated with theory of mind skills in healthy persons. This finding integrated with the previous findings of increased hostility bias and impaired theory of mind skills in clinical populations such as schizophrenia and ultra-high risk for psychosis implicate that the remediation therapy of theory of mind skills may be a potential strategy to reduce the hostility bias and paranoid symptoms in persons at ultra-high risk for psychosis and with schizophrenia.
Poster #135 MYELIN PATHOLOGY AND ITS RELATIONSHIP TO IRON HOMEOSTASIS IN SCHIZOPHRENIA Lorna A. Farrelly 1,2 , Melanie Föcking 1 , Jane English 1,2 , Gerard Cagney 2 , David Cotter 1 1 Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland; 2 School of Biomolecular & Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland Background: Schizophrenia is one of the most severe psychiatric conditions that affects 1% of the world’s population. It is characterised by a number of mental abnormalities that result in a distorted perception of reality. Neuroimaging studies are converging to suggest abnormalities in the myelin of the brain in schizophrenia. The findings of these studies are convergent with those of microarray and cytoarchitectural studies which show a reduction in myelin associated gene expression investigations and a deficit in oligodendroglial cells - the myelin producing cells of the CNS. Iron is an essential co-factor in the synthesis of lipids and is critical in oligodendroglial function and myelin formation. Additionally, oligodendrocytes are the predominant iron containing cells in the brain. Epidemiological evidence suggests that iron deficiency influences early brain development, cognitive development in children, and that maternal iron deficiency contributes to an increased risk for the development of schizophrenia (Insel et al., 2008). We hypothesise that altered iron homeostasis in the brain is implicated in the pathophysiology of schizophrenia and that this is mediated through alterations in myelin and oligodendroglial function. Methods: In this investigation the myelin proteome was enriched in post mortem tissue, characterised and differential protein expression between schizophrenia and control identified. The Stanley Array series was used. For this, white matter from the dorsolateral prefrontal lobe from 10 schizophrenia patients and 10 healthy controls, which were closely matched for age, brain pH and post mortem interval (www.stanleyresearch.org) was successfully enriched and extracted using a sucrose density gradient centrifugation protocol as per Norton and Poduslo (1973). Samples were analysed with discovery based label-free mass spectrometry using a Thermo Fisher Orbitrap™ and data were processed with the quantitative proteomics software package MaxQuant™. Data were normalised with the statistical module Perseus™. Results: Among the 280 proteins detected, we have identified proteins to be differentially expressed between schizophrenia and healthy controls (P<0.05), and these proteins are associated with cytoskeleton and myelin function. Further work based on the whole array series (n=35 per group) will validate these candidates, and specifically target all iron homeostasis proteins such as transferrin, the transferrin receptor, ferroportin and ferritin using Accurate Inclusion Mass Screening (Jaffe et al., 2008).
Discussion: This study is the first to undertake a proteomic analysis of the myelin proteome in schizophrenia. The study may provide valuable insights into the potential for pharmacological manipulation of iron homeostasis as a therapeutic tool in psychosis.
Poster #136 DISRUPTION OF CDC42 AND DUO/PAK1 PATHWAY DRIVES MYOSIN LIGHT CHAIN PHOSPHORYLATION IN SCHIZOPHRENIA María D. Rubio 1 , Vahram Haroutunian 2 , James H. Meador-Woodruff 1 1 Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA; 2 Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA Background: Recent postmortem human studies on GTPases suggest that a reduction in Duo and Cdc42 transcript expression mediates the characteristic dendritic spine loss seen in schizophrenia. The downstream pathways underlying these effectors, however, remain unknown. Murine studies show that Cdc42 and Duo activate PAK1 which in turn regulates actin polymerization by decreasing regulatory myosin light chain (MLC) and cofilin activity. Interestingly, MLC and cofilin are two main cytoskeleton regulators, critical for structural and molecular dendritic spine stability. Therefore, we proposed that in schizophrenia impaired Duo and Cdc42 downstream molecular pathways result in a disruption in MLC and/or cofilin phosphorylation state, two conditions that could lead to actin cytoskeleton disruption and dendritic spine loss. Methods: To test this hypothesis we used postmortem human brain tissue from a cohort of patients diagnosed with schizophrenia and a healthy comparison group. We focused our studies in the anterior cingulate cortex (ACC) (n=33 comparison group; n=36 schizophrenia) and dorso lateral pre frontal cortex (DLPFC) (n=29 comparison group; n=35 schizophrenia) areas. We performed western blots to detect total and phosphorylated protein expression in postmortem brain tissue. Odyssey 3.0 analytical software was used to obtain integrated intensity values for each band. Data were then analyzed using Statistica software. One-way analysis of covariance (ANCOVA) was used to analyze the data when significant correlations with potential covariates were found, otherwise, one-way analysis of variance (ANOVA) was used. Results: We found that in the ACC and DLPFC in schizophrenia there is a reduction of Duo expression that leads to a decrease in phosphorylation at the catalytic domain of PAK1. Interestingly, we found that while Cdc42 protein expression is decreased in the ACC, it remains unchanged in the DLPFC. We also show that in the ACC, the decrease in PAK1 phosphorylation leads to increased phosphorylation of MLC (pMLC) while in the DLPFC the expression levels of pMLC remain unchanged. Similar to what is described in Fragile X syndrome, neither LIMK1, a protein activated by PAK1 that leads to cofilin phosphorylation, nor cofilin phosphorylation were disrupted in any of the areas studied. Discussion: Taken together, our data suggest a novel mechanism disrupted in schizophrenia that may underlie dendritic spine loss. To our knowledge, this is the first time that a deficit in a pathway leading to cytoskeletal rearrangement has been identified in schizophrenia. In the ACC, a decrease in PAK1 activity results in an increase in pMLC, an effect that has been described to cause dendritic spine shrinkage in rodents. In the DLPFC, although Duo/PAK1 pathway is disrupted, the downstream effect does not lead to changes of pMLC, suggesting that dendritic spine stability may be regulated through different downstream mechanisms in the ACC and DLPFC areas of brains of patients with schizophrenia.
Poster #137 THE PHRENIC COMPONENT OF ACUTE SCHIZOPHRENIA - A NAME AND ITS PHYSIOLOGICAL REALITY Karl-Juergen Bär 1 , Steffen Schulz 2 , Sandy Berger 1 , Voss Andreas 2 Klinik für Psychiatrie, Universitätsklinikum Jena, Jena, Germany; 2 Department of Medical Engineering and Biotechnology, University of Applied Sciences, Jena, Germany
1
Background: Significant alterations of cardiac autonomic function were shown for patients with schizophrenia and their first-degree relatives,
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
implying a genetic association. Cardio-respiratory function, although a core physiological regulatory component, has never been assessed. Methods: To test the hypothesis of altered patterns of breathing in patients with acute schizophrenia, we assessed breathing rate, rhythm and depth, as well as heart rate variability (HRV) and cardio-respiratory coupling in patients (n=23), their first-degree relatives (n=20) and controls (n=30). Control subjects were matched for age, gender, smoking and physical fitness, and were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. Results: Patients breathe faster (p<0.001) and shallower (p<0.001) than controls most pronouncedly during exhalation. Patients’ breathing is characterized by an increased amount of middle- (p<0.001), high- (p<0.001), and very high fluctuations (p<0.001).These measures correlated with positive symptoms. Shallow breathing of patients is mirrored by a smaller tidal volume (p<0.001) without variability changes. Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives. Discussion: Changes of respiratory regulation and decreased cardiorespiratory coupling mirror profound alterations of core physiological function. In contrast to HRV changes, respiratory alterations were observed in patients only and might reflect arousal in acutely ill patients. This assumption is supported by observed changes of breathing and cardiac regulation in healthy subjects during stress. Findings are of high relevance for other research areas such as functional imaging.
Poster #138 SEMANTIC FLUENCY IS IMPAIRED BUT PHONOLOGICAL FLUENCY IS INTACT -THE KEY TO PATHOPHYSIOLOGY Timothy J. Crow 1 , Simon L. Collinson 2 , Anthony C. James 1 1 University Department of Psychiatry, Warneford Hospital, Roosevelt Drive, Oxford, Oxon, United Kingdom; 2 Department of Psychology (FASS), National University of Singapore, Singapore Background: According to De Saussure (1916) words are represented in the brain as phonological engrams (“signifiers”) and their associated meanings (“signifieds”), the relationship between the two being arbitrary and acquired in the course of learning a language. Methods: We compare the findings of studies of phonological (letters) and semantic (categories) fluency with the outcome of electrophysiological studies in psychosis of the components of language, in relation to the constraints on callosal transmission pointed out by Ringo et al. (1994). Results: In studies of verbal fluency patients with adolescent onset schizophrenia (Phillips et al., 2004) and individuals at high risk of psychosis (Magaud et al., 2010) are reported as having difficulty in retrieving words in response to categories but not to letters. In an electrophysiological experiment Angrilli et al. (2009) showed that the phonological evoked potential lateralizes to the left anteriorly, whereas the semantic evoked potential is bilateral. In patients this lateralization is diminished or reversed compared with controls. Discussion: Because phonological engrams are a limited set, and confined to one hemisphere, they are readily accessed by initial letters, also a limited set. Semantic access is less circumscribed, and depends on interhemispheric transmission. According to the “time is of the essence” concept (Ringo et al., 1994) it takes time to transmit information through the commissural fibres, and this cannot be done for processes eg phonological that are rapid and consecutive. In psychosis strength of lateralization is attenuated (Crow, 1997). Problems arise in connections between phonological (intra-) and semantic (inter-hemispheric) representations, primarily in the dominant hemisphere. Becker et al. (2010) find that amongst ultra-high risk (UHR) cases those with greater semantic deficits are more likely to proceed to overt psychosis. Amongst those who do so semantic deficits are significantly correlated with structural deficits to the left in the anterior cingulate gyrus, and to the right in the insula (Meijer et al., 2011). Thus semantic deficits in verbal fluency point to the locus of misconnexion in psychosis and its lateralization. References: Angrilli A, et al., 2009. Schizophrenia as failure of left hemispheric dominance for the phonological component of language. PLoS One 4, 1-9. Becker HE, et al., 2010, Verbal fluency as a possible predictor for psychosis. European Psychiatry 25, 105-110.
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Bokat CE, Goldberg, TE, 2003. Letter and category fluency in schizophrenic patients: a meta-analysis. Schizophr. Res. 64, 73-78. Crow, TJ, 1997. Schizophrenia as failure of hemispheric dominance for language. Trends in Neurosc. 20, 339-343. Crow, TJ, 2010. The nuclear symptoms of schizophrenia reveal the four quadrant structure of language and its deictic frame. J. Neurolinguistics. 23, 1-9. De Saussure F, 1916. Course in General Linguistics. Trans. R Harrris, 1983. Open Court, Payot. Magaud E, et al., 2010. Altered semantic but not phonological verbal fluency in young help-seeking individuals with ultra high risk of psychosis. Schizophr. Res. 123, 5358. Meijer JH, et al., 2011. Semantic fluency deficits and reduced grey matter before transition to psychosis: A voxelwise correlational analysis. Psychiatry Research Neuroimaging, 194, 1-6. Phillips, TJ, et al., 2004. Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia. Schizophr. Res. 70, 215-222. Ringo JL, et al., 1994. Time is of the essence: a conjecture that hemispheric specialisation arises from interhemispheric conduction delay. Cereb. Cort. 4, 331-343.
Poster #139 STUDY USING MAGNETOENCEPHALOGRAFY OF SPONTANEUS NEURAL ACTIVITY IN A SCHIZOPHRENIC PATIENTS Josep Tarragó 1 , Cristina Alonso 1 , Rafal Novack 2 , Oscar Pino 1 , Jose E. Rojo 1 1 HospitalGranollers-Benito Menni Granollers, Barcelona, Spain; 2 Clinica Teknon Servei de Magnetoencefalografia Barcelona, Barcelona, Spain Background: To demostrate the homogenicity of the number and location of dipoles formed during the spontaneous neuronal activity and during the execution of a CPT-IP paradigm on each group of subjects and between each group of subjects (patients with schizophrenia in relapse, patients with schizophrenia in remission and healthy controls) Methods: Inpatients and outpatients controlled in the psychiatry devices of Benito Menni General Hospital of Granollers that meet the DSM-IV criteria for schizophrenia and 20 control subjects. DESIGN: We have used a prospective, multicenter study with three parallel groups: cronic schizophrenia in relapse (9 admitted patients), stable cronic schizophrenia (9 outpatients) and 15 subjects control. All matched up in sex, age and years of schooling. VARIABLES: patients variables (clinical scales) of the MEG (spontaneous activity, number and location of the dipoles) and of fMRI (topographic location). PROCEDURE. the subjects are evaluated within the first 48 hours (lcinical and neuropsychological registries, and MEG record of spontaneous activity and CPT-IP) following its acceptance to participate. Results: We have found diffeernt density of dipoles and abnormal delta activity (slow wave) betwwen three groups. This focal slow wafe differed most bettwen temporal region of righ hemisphere and was associated with some caracteristic positive and negative symptoms. Discussion: This data could be useful in detecting people at risk or providing a marker of the disorder and its state.
Poster #140 META-ANALYSIS OF COGNITIVE DEFICITS IN ULTRA-HIGH RISK TO PSYCHOSIS Emre Bora, Christos Pantelis Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia Background: Cognitive dysfunction is one of the core features of schizophrenia and is already evident in first-episode psychosis. Recent evidence suggested that patients in prodromal phase of psychosis might also be cognitively impaired, however there are contradictory findings regarding specific abnormalities associated with clinical high risk to psychosis. Methods: A meta-analysis, following the systematic review of studies examining neurocognition in samples with clinical high risk to psychosis was conducted. Meta-regression analyses were used to examine the effects of demographic and other variables. Results: Subjects at high risk for developing psychotic disorders have worse intellectual abilities than controls in number of domains including executive functions and memory. Among these individuals, subjects who developped a psychotic disorder in the follow-up had relatively worse cognitive abilities than other subjects at high risk.
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
tentions Hostility Questionnaire (AIHQ). Participants were requested to complete a Brüne’s Theory of Mind Picture Stories task and other emotional dysregulation scales including Rosenberg’s self-esteem, Beck depression inventory, Spielberg’s state and trait anxiety inventory. Results: As predicted, multiple regression analysis showed that in ambiguous situations, hostility bias score was found to be associated with theory of mind questionnaire score (adjusted R square=0.043, beta=-0.232, t=-2.22, p=0.029, tolerance > 0.9) and in intentional situations, hostility bias score to be associated with theory of mind skills (adjusted R square=0.087, beta=-0.236, t=-2.43, p=0.017, tolerance > 0.9), depression (adjusted R square=0.129, beta=0.359, t=3.45, p=0.001, tolerance > 0.8) and self-esteem (adjusted R square=0.214, beta=0.333, t=3.20, p=0.002, tolerance > 0.8). Also blaming indexes in ambiguous and intentional situations were related with self-esteem (adjusted R square=0.067, beta=-0.278, t=-2.69, p=0.009, tolerance > 0.7) and depression (adjusted R square=0.040, beta=0.226, t=2.15, p=0.034, tolerance > 0.9) in respect. Discussion: Hostility bias in ambiguous and intentional social contexts may be associated with theory of mind skills in healthy persons. This finding integrated with the previous findings of increased hostility bias and impaired theory of mind skills in clinical populations such as schizophrenia and ultra-high risk for psychosis implicate that the remediation therapy of theory of mind skills may be a potential strategy to reduce the hostility bias and paranoid symptoms in persons at ultra-high risk for psychosis and with schizophrenia.
Poster #135 MYELIN PATHOLOGY AND ITS RELATIONSHIP TO IRON HOMEOSTASIS IN SCHIZOPHRENIA Lorna A. Farrelly 1,2 , Melanie Föcking 1 , Jane English 1,2 , Gerard Cagney 2 , David Cotter 1 1 Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland; 2 School of Biomolecular & Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland Background: Schizophrenia is one of the most severe psychiatric conditions that affects 1% of the world’s population. It is characterised by a number of mental abnormalities that result in a distorted perception of reality. Neuroimaging studies are converging to suggest abnormalities in the myelin of the brain in schizophrenia. The findings of these studies are convergent with those of microarray and cytoarchitectural studies which show a reduction in myelin associated gene expression investigations and a deficit in oligodendroglial cells - the myelin producing cells of the CNS. Iron is an essential co-factor in the synthesis of lipids and is critical in oligodendroglial function and myelin formation. Additionally, oligodendrocytes are the predominant iron containing cells in the brain. Epidemiological evidence suggests that iron deficiency influences early brain development, cognitive development in children, and that maternal iron deficiency contributes to an increased risk for the development of schizophrenia (Insel et al., 2008). We hypothesise that altered iron homeostasis in the brain is implicated in the pathophysiology of schizophrenia and that this is mediated through alterations in myelin and oligodendroglial function. Methods: In this investigation the myelin proteome was enriched in post mortem tissue, characterised and differential protein expression between schizophrenia and control identified. The Stanley Array series was used. For this, white matter from the dorsolateral prefrontal lobe from 10 schizophrenia patients and 10 healthy controls, which were closely matched for age, brain pH and post mortem interval (www.stanleyresearch.org) was successfully enriched and extracted using a sucrose density gradient centrifugation protocol as per Norton and Poduslo (1973). Samples were analysed with discovery based label-free mass spectrometry using a Thermo Fisher Orbitrap™ and data were processed with the quantitative proteomics software package MaxQuant™. Data were normalised with the statistical module Perseus™. Results: Among the 280 proteins detected, we have identified proteins to be differentially expressed between schizophrenia and healthy controls (P<0.05), and these proteins are associated with cytoskeleton and myelin function. Further work based on the whole array series (n=35 per group) will validate these candidates, and specifically target all iron homeostasis proteins such as transferrin, the transferrin receptor, ferroportin and ferritin using Accurate Inclusion Mass Screening (Jaffe et al., 2008).
Discussion: This study is the first to undertake a proteomic analysis of the myelin proteome in schizophrenia. The study may provide valuable insights into the potential for pharmacological manipulation of iron homeostasis as a therapeutic tool in psychosis.
Poster #136 DISRUPTION OF CDC42 AND DUO/PAK1 PATHWAY DRIVES MYOSIN LIGHT CHAIN PHOSPHORYLATION IN SCHIZOPHRENIA María D. Rubio 1 , Vahram Haroutunian 2 , James H. Meador-Woodruff 1 1 Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA; 2 Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA Background: Recent postmortem human studies on GTPases suggest that a reduction in Duo and Cdc42 transcript expression mediates the characteristic dendritic spine loss seen in schizophrenia. The downstream pathways underlying these effectors, however, remain unknown. Murine studies show that Cdc42 and Duo activate PAK1 which in turn regulates actin polymerization by decreasing regulatory myosin light chain (MLC) and cofilin activity. Interestingly, MLC and cofilin are two main cytoskeleton regulators, critical for structural and molecular dendritic spine stability. Therefore, we proposed that in schizophrenia impaired Duo and Cdc42 downstream molecular pathways result in a disruption in MLC and/or cofilin phosphorylation state, two conditions that could lead to actin cytoskeleton disruption and dendritic spine loss. Methods: To test this hypothesis we used postmortem human brain tissue from a cohort of patients diagnosed with schizophrenia and a healthy comparison group. We focused our studies in the anterior cingulate cortex (ACC) (n=33 comparison group; n=36 schizophrenia) and dorso lateral pre frontal cortex (DLPFC) (n=29 comparison group; n=35 schizophrenia) areas. We performed western blots to detect total and phosphorylated protein expression in postmortem brain tissue. Odyssey 3.0 analytical software was used to obtain integrated intensity values for each band. Data were then analyzed using Statistica software. One-way analysis of covariance (ANCOVA) was used to analyze the data when significant correlations with potential covariates were found, otherwise, one-way analysis of variance (ANOVA) was used. Results: We found that in the ACC and DLPFC in schizophrenia there is a reduction of Duo expression that leads to a decrease in phosphorylation at the catalytic domain of PAK1. Interestingly, we found that while Cdc42 protein expression is decreased in the ACC, it remains unchanged in the DLPFC. We also show that in the ACC, the decrease in PAK1 phosphorylation leads to increased phosphorylation of MLC (pMLC) while in the DLPFC the expression levels of pMLC remain unchanged. Similar to what is described in Fragile X syndrome, neither LIMK1, a protein activated by PAK1 that leads to cofilin phosphorylation, nor cofilin phosphorylation were disrupted in any of the areas studied. Discussion: Taken together, our data suggest a novel mechanism disrupted in schizophrenia that may underlie dendritic spine loss. To our knowledge, this is the first time that a deficit in a pathway leading to cytoskeletal rearrangement has been identified in schizophrenia. In the ACC, a decrease in PAK1 activity results in an increase in pMLC, an effect that has been described to cause dendritic spine shrinkage in rodents. In the DLPFC, although Duo/PAK1 pathway is disrupted, the downstream effect does not lead to changes of pMLC, suggesting that dendritic spine stability may be regulated through different downstream mechanisms in the ACC and DLPFC areas of brains of patients with schizophrenia.
Poster #137 THE PHRENIC COMPONENT OF ACUTE SCHIZOPHRENIA - A NAME AND ITS PHYSIOLOGICAL REALITY Karl-Juergen Bär 1 , Steffen Schulz 2 , Sandy Berger 1 , Voss Andreas 2 Klinik für Psychiatrie, Universitätsklinikum Jena, Jena, Germany; 2 Department of Medical Engineering and Biotechnology, University of Applied Sciences, Jena, Germany
1
Background: Significant alterations of cardiac autonomic function were shown for patients with schizophrenia and their first-degree relatives,
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
implying a genetic association. Cardio-respiratory function, although a core physiological regulatory component, has never been assessed. Methods: To test the hypothesis of altered patterns of breathing in patients with acute schizophrenia, we assessed breathing rate, rhythm and depth, as well as heart rate variability (HRV) and cardio-respiratory coupling in patients (n=23), their first-degree relatives (n=20) and controls (n=30). Control subjects were matched for age, gender, smoking and physical fitness, and were investigated a second time by means of a stress task to identify stress-related changes of cardio-respiratory function. Results: Patients breathe faster (p<0.001) and shallower (p<0.001) than controls most pronouncedly during exhalation. Patients’ breathing is characterized by an increased amount of middle- (p<0.001), high- (p<0.001), and very high fluctuations (p<0.001).These measures correlated with positive symptoms. Shallow breathing of patients is mirrored by a smaller tidal volume (p<0.001) without variability changes. Cardio-respiratory coupling was reduced in patients only, while HRV was decreased in patients and healthy relatives. Discussion: Changes of respiratory regulation and decreased cardiorespiratory coupling mirror profound alterations of core physiological function. In contrast to HRV changes, respiratory alterations were observed in patients only and might reflect arousal in acutely ill patients. This assumption is supported by observed changes of breathing and cardiac regulation in healthy subjects during stress. Findings are of high relevance for other research areas such as functional imaging.
Poster #138 SEMANTIC FLUENCY IS IMPAIRED BUT PHONOLOGICAL FLUENCY IS INTACT -THE KEY TO PATHOPHYSIOLOGY Timothy J. Crow 1 , Simon L. Collinson 2 , Anthony C. James 1 1 University Department of Psychiatry, Warneford Hospital, Roosevelt Drive, Oxford, Oxon, United Kingdom; 2 Department of Psychology (FASS), National University of Singapore, Singapore Background: According to De Saussure (1916) words are represented in the brain as phonological engrams (“signifiers”) and their associated meanings (“signifieds”), the relationship between the two being arbitrary and acquired in the course of learning a language. Methods: We compare the findings of studies of phonological (letters) and semantic (categories) fluency with the outcome of electrophysiological studies in psychosis of the components of language, in relation to the constraints on callosal transmission pointed out by Ringo et al. (1994). Results: In studies of verbal fluency patients with adolescent onset schizophrenia (Phillips et al., 2004) and individuals at high risk of psychosis (Magaud et al., 2010) are reported as having difficulty in retrieving words in response to categories but not to letters. In an electrophysiological experiment Angrilli et al. (2009) showed that the phonological evoked potential lateralizes to the left anteriorly, whereas the semantic evoked potential is bilateral. In patients this lateralization is diminished or reversed compared with controls. Discussion: Because phonological engrams are a limited set, and confined to one hemisphere, they are readily accessed by initial letters, also a limited set. Semantic access is less circumscribed, and depends on interhemispheric transmission. According to the “time is of the essence” concept (Ringo et al., 1994) it takes time to transmit information through the commissural fibres, and this cannot be done for processes eg phonological that are rapid and consecutive. In psychosis strength of lateralization is attenuated (Crow, 1997). Problems arise in connections between phonological (intra-) and semantic (inter-hemispheric) representations, primarily in the dominant hemisphere. Becker et al. (2010) find that amongst ultra-high risk (UHR) cases those with greater semantic deficits are more likely to proceed to overt psychosis. Amongst those who do so semantic deficits are significantly correlated with structural deficits to the left in the anterior cingulate gyrus, and to the right in the insula (Meijer et al., 2011). Thus semantic deficits in verbal fluency point to the locus of misconnexion in psychosis and its lateralization. References: Angrilli A, et al., 2009. Schizophrenia as failure of left hemispheric dominance for the phonological component of language. PLoS One 4, 1-9. Becker HE, et al., 2010, Verbal fluency as a possible predictor for psychosis. European Psychiatry 25, 105-110.
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Bokat CE, Goldberg, TE, 2003. Letter and category fluency in schizophrenic patients: a meta-analysis. Schizophr. Res. 64, 73-78. Crow, TJ, 1997. Schizophrenia as failure of hemispheric dominance for language. Trends in Neurosc. 20, 339-343. Crow, TJ, 2010. The nuclear symptoms of schizophrenia reveal the four quadrant structure of language and its deictic frame. J. Neurolinguistics. 23, 1-9. De Saussure F, 1916. Course in General Linguistics. Trans. R Harrris, 1983. Open Court, Payot. Magaud E, et al., 2010. Altered semantic but not phonological verbal fluency in young help-seeking individuals with ultra high risk of psychosis. Schizophr. Res. 123, 5358. Meijer JH, et al., 2011. Semantic fluency deficits and reduced grey matter before transition to psychosis: A voxelwise correlational analysis. Psychiatry Research Neuroimaging, 194, 1-6. Phillips, TJ, et al., 2004. Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia. Schizophr. Res. 70, 215-222. Ringo JL, et al., 1994. Time is of the essence: a conjecture that hemispheric specialisation arises from interhemispheric conduction delay. Cereb. Cort. 4, 331-343.
Poster #139 STUDY USING MAGNETOENCEPHALOGRAFY OF SPONTANEUS NEURAL ACTIVITY IN A SCHIZOPHRENIC PATIENTS Josep Tarragó 1 , Cristina Alonso 1 , Rafal Novack 2 , Oscar Pino 1 , Jose E. Rojo 1 1 HospitalGranollers-Benito Menni Granollers, Barcelona, Spain; 2 Clinica Teknon Servei de Magnetoencefalografia Barcelona, Barcelona, Spain Background: To demostrate the homogenicity of the number and location of dipoles formed during the spontaneous neuronal activity and during the execution of a CPT-IP paradigm on each group of subjects and between each group of subjects (patients with schizophrenia in relapse, patients with schizophrenia in remission and healthy controls) Methods: Inpatients and outpatients controlled in the psychiatry devices of Benito Menni General Hospital of Granollers that meet the DSM-IV criteria for schizophrenia and 20 control subjects. DESIGN: We have used a prospective, multicenter study with three parallel groups: cronic schizophrenia in relapse (9 admitted patients), stable cronic schizophrenia (9 outpatients) and 15 subjects control. All matched up in sex, age and years of schooling. VARIABLES: patients variables (clinical scales) of the MEG (spontaneous activity, number and location of the dipoles) and of fMRI (topographic location). PROCEDURE. the subjects are evaluated within the first 48 hours (lcinical and neuropsychological registries, and MEG record of spontaneous activity and CPT-IP) following its acceptance to participate. Results: We have found diffeernt density of dipoles and abnormal delta activity (slow wave) betwwen three groups. This focal slow wafe differed most bettwen temporal region of righ hemisphere and was associated with some caracteristic positive and negative symptoms. Discussion: This data could be useful in detecting people at risk or providing a marker of the disorder and its state.
Poster #140 META-ANALYSIS OF COGNITIVE DEFICITS IN ULTRA-HIGH RISK TO PSYCHOSIS Emre Bora, Christos Pantelis Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia Background: Cognitive dysfunction is one of the core features of schizophrenia and is already evident in first-episode psychosis. Recent evidence suggested that patients in prodromal phase of psychosis might also be cognitively impaired, however there are contradictory findings regarding specific abnormalities associated with clinical high risk to psychosis. Methods: A meta-analysis, following the systematic review of studies examining neurocognition in samples with clinical high risk to psychosis was conducted. Meta-regression analyses were used to examine the effects of demographic and other variables. Results: Subjects at high risk for developing psychotic disorders have worse intellectual abilities than controls in number of domains including executive functions and memory. Among these individuals, subjects who developped a psychotic disorder in the follow-up had relatively worse cognitive abilities than other subjects at high risk.