- Email: [email protected]
MEASUREMENT OF MORPHOLOGICAL CHANGES IN SCHIZOPHRENIC PATIENTS USING BRAIN MAGNETIC RESONANCE IMAGING
224
Abstracts
Poster 95 EVIDENCE FOR WIDESPREAD THINNING OF THE CEREBRAL CORTEX IN PATIENTS WITH FIRST-EPISODE PSYCHOSIS WITH POOR INSIGHT Lisa Buchy1,2,3, Bodnar D. Michael1,2,3, Claude Lepage3, Yasser Ad-Dab'bagh3, Karen Sergerie1,3, Ashok Malla2,4, Ridha Joober2,4, Alan Evans3, Martin Lepage1,2,3,4 1 Brain Imaging Group, Douglas Mental Health University Institute Verdun, QC, Canada; 2Prevention and Early Intervention Program for Psychoses, Douglas Mental Health University Institute Verdun, QC, Canada; 3 Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University Montreal, QC, Canada; 4Department of Psychiatry, McGill University Montreal, QC, Canada Background: Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. In the current work, we used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Methods: Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the neuroanatomical basis of insight. Results: Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in the left middle frontal (Dorsolateral prefrontal cortex, BA9) and left inferior temporal gyri (BA20). Poorer awareness of treatment need and efficacy was associated with widespread cortical thinning, most prominently in the left medial frontal gyrus (BA6), left precuneus (BA7) and left temporal gyri (BA20/38/39). No significant associations emerged between any insight measure and gray matter volumes using voxel-based morphometry. Discussion: The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of a psychotic disorder. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need/efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes, as previously suggested. doi:10.1016/j.schres.2010.02.323
Poster 96 GLOBAL AND LOCAL CONNECTIVITY CHANGES IN SCHIZOPHRENIA INVESTIGATED BY DIFFUSION CONNECTOME Leila Cammoun1, Djalel Meskaldji1, Xavier Gigandet1, Jean Philippe Thiran1, Reto Meuli2, Michel Cuenod3, Patric Hagmann2, Thi Kim Do3 1 Signal Processing Lab5, Ecole Polytechnique Fédérale de Lausanne Lausanne Switzerland; 2Department of Radiology, University Hospital Center and University of Lausanne Lausanne Switzerland; 3Center for Psychiatric Neuroscience, Department of Psychiatry, University Hospital Center and University of Lausanne Lausanne Switzerland Background: New ways of representing diffusion data emerged recently and achieved to create structural connectivity maps in healthy
brains (Hagmann P et al. (2008)). These maps have the capacity to study alterations over the entire brain at the connection and network level. This is of high interest in complex disconnection diseases like schizophrenia. In this Pathology where multiple lines of evidence suggest the association of the pathology with abnormalities in neural circuitry and impaired structural connectivity, the diffusion imaging has been widely applied. Despite the large findings, most of the research using the diffusion just uses some scalar map derived from diffusion to show that some markers of white matter integrity are diminished in several areas of the brain (Kyriakopoulos M et al (2008)). Thanks to the structural connection matrix constructed by the whole brain tractography, we report in this work the network connectivity alterations in the schizophrenic patients. Methods: We investigated 13 schizophrenic patients as assessed by the DIGS (Diagnostic Interview for genetic studies, DSM IV criteria) and 13 healthy controls. We have got from each volunteer a DT-MRI as well as Qball imaging dataset and a high resolution anatomic T1 performed during the same session; with a 3 T clinical MRI scanner. The controls were matched on age, gender, handedness, and parental social economic-status. For all the subjects, a low resolution connection matrix is obtained by dividing the cortex into 66 gyral based ROIs. A higher resolution matrix is constructed using 250 ROIs as described in Hagmann P et al. (2008). These ROIs are respectively used jointly with the diffusion tractography to construct the high and low resolution densities connection matrices for each subject. In a first step the matrices of the groups are compared in term of connectivity, and not in term of density to check if the pathological group shows a loss of global connectivity. In this context the density connection matrices were binarized. As some local connectivity changes were also suspected, especially in frontal and temporal areas, we have also looked for the areas where the connectivity showed significant changes. Results: The statistical analysis revealed a significant loss of global connectivity in the schizophrenic's brains at level 5%. Furthermore, by constructing specific statistics which represent local connectivity within the anatomical regions (66 ROIs) using the data obtained by the finest resolution (250 ROIs) to improve the robustness, we found the regions that cause this significant loss of connectivity. The significance is observed after multiple testing corrections by the False Discovery Rate. Discussion: The detected regions are almost the same as those reported in the literature as the involved regions in schizophrenia. Most of the connectivity decreases are noted in both hemispheres in the fronto-frontal and temporo-temporal regions as well as some temporal ROIs with their adjacent ROIs in parietal and occipital lobes.
doi:10.1016/j.schres.2010.02.324
Poster 97 MEASUREMENT OF MORPHOLOGICAL CHANGES IN SCHIZOPHRENIC PATIENTS USING BRAIN MAGNETIC RESONANCE IMAGING Jin Hee Choi1, Kang Kim2, Tae Yong Kim1, Moon Yong Chung1, Hyoung Seok So1 1 Seoul Veterans Hospital Seoul South Korea; 2SEIFE Mental Hospital Seoul South Korea Background: This study was performed to compare and measure the changes of corpus callosum of the schizophrenic patients with those of controls, to compare according to clinical symptoms,onset age.
Abstracts
Methods: Brain magnetic resonance imaging study was performed in 38 schizophrenic patients and 28 controls,and the authors measured cerebral area,anterior,middle,posterior callosal areas, vertical width,perpendicular width and maximal horizontal callosal length.The schizophreic patients were assessed by the PANSS. To correct cerebral areas, ANCOVA was used with cerebral area as covariants. And two tailed t-test,ANOVA were used to compare callosal measurements according to subgroups. Results: The schizophrenic patients,compared with controls, were significantly wider in posterior callosal area and thinner in anterior vertical width. The schizophrenic patients with prominent positive symptoms were significantly wider and thicker in middle callosal area,anterior middle vertical width than controls,and those with prominent negative symptoms were significantly thinner in posterior vertical width than those with prominent positive symptoms and wider in anterior area than controls. Early onset patients were significantly thicker in middle perpendicular area than controls. Discussion: There were various controversial findings about corpus callosal pathology of the schizophrenic patients. This study,after correction of cerebral area,revealed increased size of several parts of callosal regions,and then it suggested neurodevelopmental abnormalities. And also significant differences in callosal regions according positive and negative symptoms suggested that these reflected the heterogeneities of schizophrenia.
225
phrenia patients and 28 age and gender matched healthy control subjects. Baseline and follow-up brain images were analyzed using tensor based morphometry (TBM). Voxel-wise group comparisons were performed with SPM5. Small volume correction was performed for the striatum, hippocampus and ventricles, using a FDRcorrection (p < 0.05) to control for multiple comparisons. Additionally, volumetric estimates were derived and analyzed. Effects of medication, including dose-dependent effects, and associations with psychopathology (PANSS-scores) were assessed. Results: Patients had significant striatal and hippocampal volume loss over the six months treatment period. The striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses. Conversely, hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses. Clinically, higher baseline positive symptoms were associated with more striatal and hippocampal volume loss over time. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement on negative symptoms. Discussion: Progressive regional volume loss in quetiapine-treated first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying progressive brain changes, specific antipsychotic compounds and clinical symptoms warrant further research. doi:10.1016/j.schres.2010.02.327
doi:10.1016/j.schres.2010.02.325
Poster 100 Poster not available
Poster 98 Poster not available doi:10.1016/j.schres.2010.02.326
Poster 99 REGIONAL BRAIN CHANGES IN INITIALLY ANTIPSYCHOTIC-NAïVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS TREATED WITH QUETIAPINE: RELATION TO DOSE AND PSYCHOPATHOLOGY Bjørn H. Ebdrup1,2,3, Arnold Skimminge3, Hans Rasmussen1,2, Bodil Aggernaes1, Bob Oranje1,2, Henrik Lublin1,2, William Baaré3,4, Birte Glenthoj1,2 1 Center for Neuropsychiatric Schizophrenia Research, CNSR Glostrup, Glostrup, Denmark; 2Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS Glostrup, Glostrup, Denmark; 3Danish Research Centre for Magnetic Resonance, DRCMR Hvidovre, Copenhagen, Denmark; 4Center for Integrated Molecular Brain Imaging, CIMBI Copenhagen, Copenhagen, Denmark Background: MRI studies have shown progressive brain alterations in the course of schizophrenia. Whereas first-generation antipsychotics have been associated with striatal volume increases, the effects of second-generation antipsychotics (SGA) on striatal volumes are unclear. Neuroprotective effects of SGAs have been suggested on hippocampal volumes, whereas ventricular enlargement may be associated with clinical outcome. Dose-dependent volumetric effects of individual SGAs have been scarcely investigated. In this study, we examined structural brain changes in initially antipsychotic-naïve first-episode schizophrenia patients after six months of mono-therapy with quetiapine. Methods: High-resolution 3D T1-weighted magnetic resonance imaging scans were obtained on a 3 Tesla scanner at baseline and after six months in 22 antipsychotic-naïve first-episode schizo-
doi:10.1016/j.schres.2010.02.328
Poster 101 FRONTAL CORTICAL THICKNESS IS ASSOCIATED WITH CLINICAL IMPROVEMENT OF NEGATIVE SYMPTOMS IN MALE ADOLESCENTS WITH EARLY-ONSET FIRST-EPISODE PSYCHOSIS Margarita Garcia-Amador1, Jansen Joost1,2, Santiago Reig1,2, Mara Parellada1, Dolores Moreno1, Carmen Moreno1, Maria Mayoral1,2, Montserrat Grael3, Manuel Desco2, Celso Arango1 1 Hospital Universitario Gregorio Marañón, Department of Psychiatry, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Madrid, Madrid, Spain; 2Hospital Universitario Gregorio Marañón, Department of Experimental Surgery and Medicine, and CIBERSAM Madrid, Madrid, Spain; 3Hospital Universitario Infantil Niño Jesús, Department of Psychiatry Madrid, Madrid, Spain Background: First-episode psychosis in adults and adolescents is associated with volume deficits in the frontal cortex. It is unclear if deficits in cortical thickness and/or cortical surface and/or cortical gyrification underlie the patient-control differences in cortical volume. In addition, in adult and adolescent patients with psychosis it's not evident if cortical structural brain abnormalities are related to change in clinical symptoms over time. The current study was designed to compare frontal cortical thickness, surface, and gyrification between male adolescents with early-onset firstepisode psychosis (EOP) and healthy controls. Within patients, the relationship between frontal cortical morphology and change in clinical symptoms over a two-year clinical follow up period was investigated. Methods: Baseline Magnetic Resonance Imaging (MRI) brain scans were obtained from 49 adolescent EOP patients, and 34 healthy controls. Mean age was 15 years for patients and controls, and all patients had less than six months of psychotic symptoms at study
Abstracts
Poster 95 EVIDENCE FOR WIDESPREAD THINNING OF THE CEREBRAL CORTEX IN PATIENTS WITH FIRST-EPISODE PSYCHOSIS WITH POOR INSIGHT Lisa Buchy1,2,3, Bodnar D. Michael1,2,3, Claude Lepage3, Yasser Ad-Dab'bagh3, Karen Sergerie1,3, Ashok Malla2,4, Ridha Joober2,4, Alan Evans3, Martin Lepage1,2,3,4 1 Brain Imaging Group, Douglas Mental Health University Institute Verdun, QC, Canada; 2Prevention and Early Intervention Program for Psychoses, Douglas Mental Health University Institute Verdun, QC, Canada; 3 Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University Montreal, QC, Canada; 4Department of Psychiatry, McGill University Montreal, QC, Canada Background: Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. In the current work, we used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Methods: Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the neuroanatomical basis of insight. Results: Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in the left middle frontal (Dorsolateral prefrontal cortex, BA9) and left inferior temporal gyri (BA20). Poorer awareness of treatment need and efficacy was associated with widespread cortical thinning, most prominently in the left medial frontal gyrus (BA6), left precuneus (BA7) and left temporal gyri (BA20/38/39). No significant associations emerged between any insight measure and gray matter volumes using voxel-based morphometry. Discussion: The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of a psychotic disorder. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need/efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes, as previously suggested. doi:10.1016/j.schres.2010.02.323
Poster 96 GLOBAL AND LOCAL CONNECTIVITY CHANGES IN SCHIZOPHRENIA INVESTIGATED BY DIFFUSION CONNECTOME Leila Cammoun1, Djalel Meskaldji1, Xavier Gigandet1, Jean Philippe Thiran1, Reto Meuli2, Michel Cuenod3, Patric Hagmann2, Thi Kim Do3 1 Signal Processing Lab5, Ecole Polytechnique Fédérale de Lausanne Lausanne Switzerland; 2Department of Radiology, University Hospital Center and University of Lausanne Lausanne Switzerland; 3Center for Psychiatric Neuroscience, Department of Psychiatry, University Hospital Center and University of Lausanne Lausanne Switzerland Background: New ways of representing diffusion data emerged recently and achieved to create structural connectivity maps in healthy
brains (Hagmann P et al. (2008)). These maps have the capacity to study alterations over the entire brain at the connection and network level. This is of high interest in complex disconnection diseases like schizophrenia. In this Pathology where multiple lines of evidence suggest the association of the pathology with abnormalities in neural circuitry and impaired structural connectivity, the diffusion imaging has been widely applied. Despite the large findings, most of the research using the diffusion just uses some scalar map derived from diffusion to show that some markers of white matter integrity are diminished in several areas of the brain (Kyriakopoulos M et al (2008)). Thanks to the structural connection matrix constructed by the whole brain tractography, we report in this work the network connectivity alterations in the schizophrenic patients. Methods: We investigated 13 schizophrenic patients as assessed by the DIGS (Diagnostic Interview for genetic studies, DSM IV criteria) and 13 healthy controls. We have got from each volunteer a DT-MRI as well as Qball imaging dataset and a high resolution anatomic T1 performed during the same session; with a 3 T clinical MRI scanner. The controls were matched on age, gender, handedness, and parental social economic-status. For all the subjects, a low resolution connection matrix is obtained by dividing the cortex into 66 gyral based ROIs. A higher resolution matrix is constructed using 250 ROIs as described in Hagmann P et al. (2008). These ROIs are respectively used jointly with the diffusion tractography to construct the high and low resolution densities connection matrices for each subject. In a first step the matrices of the groups are compared in term of connectivity, and not in term of density to check if the pathological group shows a loss of global connectivity. In this context the density connection matrices were binarized. As some local connectivity changes were also suspected, especially in frontal and temporal areas, we have also looked for the areas where the connectivity showed significant changes. Results: The statistical analysis revealed a significant loss of global connectivity in the schizophrenic's brains at level 5%. Furthermore, by constructing specific statistics which represent local connectivity within the anatomical regions (66 ROIs) using the data obtained by the finest resolution (250 ROIs) to improve the robustness, we found the regions that cause this significant loss of connectivity. The significance is observed after multiple testing corrections by the False Discovery Rate. Discussion: The detected regions are almost the same as those reported in the literature as the involved regions in schizophrenia. Most of the connectivity decreases are noted in both hemispheres in the fronto-frontal and temporo-temporal regions as well as some temporal ROIs with their adjacent ROIs in parietal and occipital lobes.
doi:10.1016/j.schres.2010.02.324
Poster 97 MEASUREMENT OF MORPHOLOGICAL CHANGES IN SCHIZOPHRENIC PATIENTS USING BRAIN MAGNETIC RESONANCE IMAGING Jin Hee Choi1, Kang Kim2, Tae Yong Kim1, Moon Yong Chung1, Hyoung Seok So1 1 Seoul Veterans Hospital Seoul South Korea; 2SEIFE Mental Hospital Seoul South Korea Background: This study was performed to compare and measure the changes of corpus callosum of the schizophrenic patients with those of controls, to compare according to clinical symptoms,onset age.
Abstracts
Methods: Brain magnetic resonance imaging study was performed in 38 schizophrenic patients and 28 controls,and the authors measured cerebral area,anterior,middle,posterior callosal areas, vertical width,perpendicular width and maximal horizontal callosal length.The schizophreic patients were assessed by the PANSS. To correct cerebral areas, ANCOVA was used with cerebral area as covariants. And two tailed t-test,ANOVA were used to compare callosal measurements according to subgroups. Results: The schizophrenic patients,compared with controls, were significantly wider in posterior callosal area and thinner in anterior vertical width. The schizophrenic patients with prominent positive symptoms were significantly wider and thicker in middle callosal area,anterior middle vertical width than controls,and those with prominent negative symptoms were significantly thinner in posterior vertical width than those with prominent positive symptoms and wider in anterior area than controls. Early onset patients were significantly thicker in middle perpendicular area than controls. Discussion: There were various controversial findings about corpus callosal pathology of the schizophrenic patients. This study,after correction of cerebral area,revealed increased size of several parts of callosal regions,and then it suggested neurodevelopmental abnormalities. And also significant differences in callosal regions according positive and negative symptoms suggested that these reflected the heterogeneities of schizophrenia.
225
phrenia patients and 28 age and gender matched healthy control subjects. Baseline and follow-up brain images were analyzed using tensor based morphometry (TBM). Voxel-wise group comparisons were performed with SPM5. Small volume correction was performed for the striatum, hippocampus and ventricles, using a FDRcorrection (p < 0.05) to control for multiple comparisons. Additionally, volumetric estimates were derived and analyzed. Effects of medication, including dose-dependent effects, and associations with psychopathology (PANSS-scores) were assessed. Results: Patients had significant striatal and hippocampal volume loss over the six months treatment period. The striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses. Conversely, hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses. Clinically, higher baseline positive symptoms were associated with more striatal and hippocampal volume loss over time. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement on negative symptoms. Discussion: Progressive regional volume loss in quetiapine-treated first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying progressive brain changes, specific antipsychotic compounds and clinical symptoms warrant further research. doi:10.1016/j.schres.2010.02.327
doi:10.1016/j.schres.2010.02.325
Poster 100 Poster not available
Poster 98 Poster not available doi:10.1016/j.schres.2010.02.326
Poster 99 REGIONAL BRAIN CHANGES IN INITIALLY ANTIPSYCHOTIC-NAïVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS TREATED WITH QUETIAPINE: RELATION TO DOSE AND PSYCHOPATHOLOGY Bjørn H. Ebdrup1,2,3, Arnold Skimminge3, Hans Rasmussen1,2, Bodil Aggernaes1, Bob Oranje1,2, Henrik Lublin1,2, William Baaré3,4, Birte Glenthoj1,2 1 Center for Neuropsychiatric Schizophrenia Research, CNSR Glostrup, Glostrup, Denmark; 2Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS Glostrup, Glostrup, Denmark; 3Danish Research Centre for Magnetic Resonance, DRCMR Hvidovre, Copenhagen, Denmark; 4Center for Integrated Molecular Brain Imaging, CIMBI Copenhagen, Copenhagen, Denmark Background: MRI studies have shown progressive brain alterations in the course of schizophrenia. Whereas first-generation antipsychotics have been associated with striatal volume increases, the effects of second-generation antipsychotics (SGA) on striatal volumes are unclear. Neuroprotective effects of SGAs have been suggested on hippocampal volumes, whereas ventricular enlargement may be associated with clinical outcome. Dose-dependent volumetric effects of individual SGAs have been scarcely investigated. In this study, we examined structural brain changes in initially antipsychotic-naïve first-episode schizophrenia patients after six months of mono-therapy with quetiapine. Methods: High-resolution 3D T1-weighted magnetic resonance imaging scans were obtained on a 3 Tesla scanner at baseline and after six months in 22 antipsychotic-naïve first-episode schizo-
doi:10.1016/j.schres.2010.02.328
Poster 101 FRONTAL CORTICAL THICKNESS IS ASSOCIATED WITH CLINICAL IMPROVEMENT OF NEGATIVE SYMPTOMS IN MALE ADOLESCENTS WITH EARLY-ONSET FIRST-EPISODE PSYCHOSIS Margarita Garcia-Amador1, Jansen Joost1,2, Santiago Reig1,2, Mara Parellada1, Dolores Moreno1, Carmen Moreno1, Maria Mayoral1,2, Montserrat Grael3, Manuel Desco2, Celso Arango1 1 Hospital Universitario Gregorio Marañón, Department of Psychiatry, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Madrid, Madrid, Spain; 2Hospital Universitario Gregorio Marañón, Department of Experimental Surgery and Medicine, and CIBERSAM Madrid, Madrid, Spain; 3Hospital Universitario Infantil Niño Jesús, Department of Psychiatry Madrid, Madrid, Spain Background: First-episode psychosis in adults and adolescents is associated with volume deficits in the frontal cortex. It is unclear if deficits in cortical thickness and/or cortical surface and/or cortical gyrification underlie the patient-control differences in cortical volume. In addition, in adult and adolescent patients with psychosis it's not evident if cortical structural brain abnormalities are related to change in clinical symptoms over time. The current study was designed to compare frontal cortical thickness, surface, and gyrification between male adolescents with early-onset firstepisode psychosis (EOP) and healthy controls. Within patients, the relationship between frontal cortical morphology and change in clinical symptoms over a two-year clinical follow up period was investigated. Methods: Baseline Magnetic Resonance Imaging (MRI) brain scans were obtained from 49 adolescent EOP patients, and 34 healthy controls. Mean age was 15 years for patients and controls, and all patients had less than six months of psychotic symptoms at study