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CONNECTION BETWEEN THE CORPUS CALLOSUM AND PREDISPOSITION TOWARDS HALLUCINATIONS – EVIDENCE FROM SCHIZOPHRENIA PATIENTS AND UNAFFECTED RELATIVES
228
Abstracts
2.6 mm vs 2.4 mm, F = 12.9, p < 0.001, effect size (ES) = 0.13), decreased frontal surface (705.9 cm2 vs 696.8 cm2, F = 3.9, p = 0.05, ES= 0.05), and decreased frontal gyrification (3.0 vs 2.9, F = 3.5, p = 0.06, ES = 0.05). Patients showed significant reduction in positive (t = 10.1, p < 0.001) and negative symptoms (t = 5.5, p < 0.001). Reduction in negative symptoms was positively correlated with baseline negative symptom severity (Pearson product-moment correlation coefficient (r) = 0.6, p < 0.001), meaning that a higher PANSS score at baseline was associated with more clinical improvement over time. Reduction in negative symptoms was positively correlated to frontal cortical thickness (r= 0.5, p = 0.003), meaning that greater clinical improvement was related with a thinner frontal cortex at baseline. This correlation remained significant after controlling for baseline negative symptom severity (r= 0.4, p = 0.003). Discussion: EOP in male adolescents is associated with a thinner frontal cortex. Frontal surface and gyrification may be less affected in EOP. Interestingly, our finding of a relationship between thinner frontal cortex and greater clinical improvement over time points to previous findings in longitudinal studies of grey matter changes in children, adolescents and adults with schizophrenia (Gur et al 1998, DeLisi et al 1998, Sporn et al 2003, Vidal et al 2006). In children and adolescents with early-onset schizophrenia, progressive loss of grey matter was correlated with greater clinical improvement (Sporn et al 2003) and less frontal grey matter was related to less symptoms at follow up (Vidal et al 2006). A full replication of these previous findings necessitates longitudinal MRI measurements, which is a future goal.
doi:10.1016/j.schres.2010.02.333
Poster 106 HIGH RESOLUTION DEFORMATION-BASED MORPHOMETRY REVEALS A COMPLEX PATTERN OF BRAIN MORPHOLOGY CHANGES IN SCHIZOPHRENIA Tomas Kasparek1, Daniel Schwarz2, Radovan Prikryl1, Radek Marecek3, Michal Mikl3, Jiri Vanicek4, Eva Ceskova1 1 Department of Psychiatry, Faculty Hospital Brno-Bohunice and Masaryk University Brno Czech Republic; 2Institute of biostatistics and analyses Brno Czech Republic; 3Department of Neurology, Masaryk University Brno Czech Republic; 4Department of Imaging Methods Brno Czech Republic Background: Schizophrenia is linked with changes of brain morphology in gray, white matter and cerebrospinal spaces. Analysis of high-resolution deformations field have a potential to detect changes in all these three compartments. Methods: We present results of a high-resolution deformationbased morphometric study of first-episode (n = 49), chronic (n = 19) schizophrenia patients, and healthy controls (n = 127). Results: Schizophrenia subjects showed volume reduction of prefrontal lobe – both cortical and subcortical parts, cingulate gyrus, in temporal, parietal, as well as occipital lobe, in thalamus, and cerebellum. They also showed increase in of lateral ventricles, basal ganglia, and in many subarachnoidal spaces surrounding mainly frontal and temporal cortex. There were no differences between the two schizophrenia groups, in separate analysis between first-episode or chronic subjects with healthy controls analogues pattern of brain changes emerged. Discussion: Using high-resolution deformation-based morphometry it is possible to capture the complex pattern of brain morphology changes in schizophrenia. These features might be advatageous in applications that try to classify subjects with schizophrenia based on neuroimaging results.
This study was supported by a research grant from the Ministry of Health, Czech Republic No. NR 9893-4. doi:10.1016/j.schres.2010.02.334
Poster 107 LONGITUDINAL VOXEL-BASED MORPHOMETRIC STUDY TO EVALUATE PROGRESSIVE GRAY MATER CHANGES IN FIRST-EPISODE SCHIZOPHRENIA Yasuhiro Kawasaki1,2, Mikio Kido1, Tsutomu Takahashi1,2, Kazue Nakamura1, Michio Suzuki1,2 1 University of Toyama Toyama, Toyama, Japan; 2JST, CREST Tokyo, Tokyo, Japan Background: Although longitudinal magnetic resonance imaging (MRI) studies have shown that various brain regions undergo progressive tissue loss during the early phases of schizophrenia, regional pattern of these changes remain unclear. Methods: Longitudinal MRI data were obtained from 18 (12 male and 6 female) patients with first-episode schizophrenia and 20 (11 male and 9 female) healthy controls and at baseline and follow-up with mean scan interval of 2.7 years. To compare gray matter changes over time between patients and controls were evaluated with voxel-based morphometry (VBM) using SPM8 following the longitudinal DARTEL protocol. Results: In both groups of patient and control longitudinal gray mater reduction was observed in various brain regions including lateral and medial frontal regions and superior temporal region. Excessive decrease in gray matter was found in patients as compared to healthy controls in the left superior temporal region and right inferior frontal region. Discussion: Our findings suggest that there are differing longitudinal gray matter changes in patients with schizophrenia during the early phases of the illness as compared to healthy individuals. doi:10.1016/j.schres.2010.02.335
Poster 108 CONNECTION BETWEEN THE CORPUS CALLOSUM AND PREDISPOSITION TOWARDS HALLUCINATIONS – EVIDENCE FROM SCHIZOPHRENIA PATIENTS AND UNAFFECTED RELATIVES Christian Knöchel1, Viola Oertel-Knöchel1, Ralf Schönmeyer1, Anna Rotarska-Jagiela1, Vincent van de Ven2, Corinna Haenschel3, Peter Uhlhaas1, Johannes Pantel1, David E.J. Linden3 1 Frankfurt, Hessen, Germany; 2Maastricht, Netherlands, Netherlands; 3 Bangor, Bangor, Wales Background: In the current study, we applied an automatic segmentation method (Schönmeyer et al., 2007) to examine anatomical differences, as indexed by volumetry and two diffusion values (FA and MD (DTI), in the most important connection between the two hemispheres (Trepel, 1999), the corpus callosum (CC). Methods: We measured 16 chronic schizophrenia (SZ) patients, and age, gender, handedness and parental years of education matched first degree relatives and controls. Results: The results showed significant volume loss for SZ patients in the whole CC volume, as well as in the subparts posterior genu, isthmus and splenium. In addition, similar results were found for the FA values (DTI) of the whole CC, the inferior genu, the superior genu and the isthmus. However, the MD values of the whole CC and the isthmus showed increased compactness and decreased inter-
Abstracts
cellular space (Beaulieu, 2002) for SZ patients. Furthermore, the relatives had intermediate values in the volumetric and fiber integrity measurements. Discussion: In conclusion, the results conform to the hypothesis of a pathological connectivity (hypoconnectivity) between different brain regions (Friton and Frith, 1995; Friston, 1998). We provide evidences for a connection between volume loss and loss of fiber integrity in SZ patients and their unaffected relatives, which is associated with the individual psychopathology, as assessed by the PANSS (Kay et al., 1987). doi:10.1016/j.schres.2010.02.336
Poster 109 STRUCTURAL NEURAL CORRELATES OF VERBAL MEMORY IN FIRST EPISODE SCHIZOPHRENIA Martin Lepage1,2, Tom Howells1, Lisa Buchy1,2, Audrey Benoit1, Michael Bodnar1,2, Ridha Joober1,2, Ashok Malla1,2 1 Douglas Institute Verdun, Quebec, Canada; 2McGill University Montreal, Quebec, Canada Background: People with schizophrenia consistently show verbal memory impairment even in the early stages of the disease. Several studies have examined the functional neural correlates of verbal memory and have observed reduced activity in the medial temporal lobe and several areas of the prefrontal cortex, among other regions. Fewer studies however, have systematically explored structural neural correlates of verbal memory following first episode schizophrenia. We used two complementary imaging techniques, namely hippocampal volumetry and cortical thickness, to explore structural correlates of verbal memory. Methods: Sixty-five patients with a first episode of schizophrenia spectrum disorder and fifty-six healthy controls were matched on sociodemographical variables. A T1 structural MRI scan was used to perform the cortical thickness analyses and the segmentation of the hippocampus into a head, body and tail area. Multiple standardized verbal memory tests were combined into a global measure. Results: Compared to healthy controls, patients exhibited significant verbal memory impairment. Correlations between hippocampal volume and verbal memory performance revealed a significant positive association that was limited to the left hippocampal head in the healthy controls. No significant associations were observed in the patient group. The cortical thickness analyses revealed an extensive network of brain regions positively correlated with memory performance, including a large section of the left prefrontal cortex in the healthy group relative to the patient group. Discussion: These results suggest that the coupling between verbal memory and structural neural correlates is significantly reduced in first episode schizophrenia. doi:10.1016/j.schres.2010.02.337
Poster 110 ATYPICAL ANTIPSYCHOTICS: CLINICAL IMPROVEMENTS AND STRUCTURAL CEREBRAL CHANGES Genevieve Letourneau1,2,3, Emmanuel Stip1,2,3, Lahcen Ait Bentaleb1,2,3, Benjamin Stip3, Adham Mancini-Marie3, Stephane Potvin3 1 University of Montreal Montréal, QC, Canada; 2Hôpital Louis-H. Lafontaine Montréal, QC, Canada; 3Centre de recherche Fernand-Seguin Montréal, QC, Canada
229
Background: Cerebral anatomical differences have been widely described in schizophrenia patients compared to control subjects. Many studies have suggested a time-related progression of those differences, the severity of which has also been correlated with clinical characteristics of the disease. According to some recent studies, antipsychotic medications might also modulate cerebral anatomical changes in schizophrenia patients. Some results suggest a slower deterioration or even a normalization process of the cerebral structures associated with atypical antipsychotics. The present study aims to document and compare the cerebral structural effects of quetiapine and olanzapine in schizophrenia patients. Methods: We selected 29 patients suffering from schizophrenia. At the beginning of the study, 17 patients were started on a medication of olanzapine and 12 patients on a medication of quetiapine. Within the first week of the study, all patients passed a Magnetic Resonance Imaging examination, which they passed a second time at the end of the study. All analyses were made using Voxel-BasedMorphometry for Statistical Parametric Mapping (SPM)-8. Clinical status of all patients was monitored using PANSS. Results: The patients taking olanzapine took the second examination in average 4 months after the first one, while the patients taking quetiapine did so in average 5.5 months after the first one. Patients on quetiapine showed relative grey matter increases in frontal regions such as the orbitofrontal and middle frontal cortex and in the cerebellum and in cingulate regions. Patients on olanzapine showed relative grey matter increases mostly in frontal and temporal regions. Clinical differences were also noted as the quetiapine group patients had more prominent negative symptoms while the olanzapine group patients mostly displayed positive psychotic symptoms (such as hallucinations) at the beginning of the study. Both patients groups showed clinical improvement throughout the study. Discussion: Our study results confirm that treatment with atypical atypsychotics, such as Quetiapine and Olanzapine, can be associated with structural cerebral changes. Grey matter increases were mostly observed in frontal and cingulate regions, in a population of schizophrenia patients presenting mostly negative symptoms and treated with Quetiapine. These cerebral structures variations could be correlated to Negative Symptoms Scores after a treatment of Quetiapine. Grey matter increases were observed mostly in temporal and frontal regions, in a population of schizophrenia patients presenting mostly positive symptoms and treated with Olanzapine. These cerebral structures variations were significantly correlated with improvements on both positive items and global scores of PANSS evaluations after a treatment of Olanzapine. Our study results suggest that clinical improvement with atypical antipsychotics treatment could be associated with specific grey matter increases in schizophrenia patients.
doi:10.1016/j.schres.2010.02.338
Poster 111 MAGNETIC RESONANCE IMAGING OF THE SUPERIOR TEMPORAL GYRUS IN MONOZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA
Sheena Waters-Metenier1, Timothea Toulopoulou1, Alexander Sumich2, Ulrich Ettinger1,3, Robin Murray1, Marco Picchioni1,4 1 Psychological Medicine and Psychiatry, Institute of Psychiatry, KCL London United Kingdom; 2Brain Imaging and Analysis Unit, Institute of Psychiatry, KCL London United Kingdom; 3Munich Center for Neurosciences-Brain & Mind, Ludwig-Maximilians-Universität Munich Germany; 4Forensic Mental Health Science, KCL London United Kingdom
Abstracts
2.6 mm vs 2.4 mm, F = 12.9, p < 0.001, effect size (ES) = 0.13), decreased frontal surface (705.9 cm2 vs 696.8 cm2, F = 3.9, p = 0.05, ES= 0.05), and decreased frontal gyrification (3.0 vs 2.9, F = 3.5, p = 0.06, ES = 0.05). Patients showed significant reduction in positive (t = 10.1, p < 0.001) and negative symptoms (t = 5.5, p < 0.001). Reduction in negative symptoms was positively correlated with baseline negative symptom severity (Pearson product-moment correlation coefficient (r) = 0.6, p < 0.001), meaning that a higher PANSS score at baseline was associated with more clinical improvement over time. Reduction in negative symptoms was positively correlated to frontal cortical thickness (r= 0.5, p = 0.003), meaning that greater clinical improvement was related with a thinner frontal cortex at baseline. This correlation remained significant after controlling for baseline negative symptom severity (r= 0.4, p = 0.003). Discussion: EOP in male adolescents is associated with a thinner frontal cortex. Frontal surface and gyrification may be less affected in EOP. Interestingly, our finding of a relationship between thinner frontal cortex and greater clinical improvement over time points to previous findings in longitudinal studies of grey matter changes in children, adolescents and adults with schizophrenia (Gur et al 1998, DeLisi et al 1998, Sporn et al 2003, Vidal et al 2006). In children and adolescents with early-onset schizophrenia, progressive loss of grey matter was correlated with greater clinical improvement (Sporn et al 2003) and less frontal grey matter was related to less symptoms at follow up (Vidal et al 2006). A full replication of these previous findings necessitates longitudinal MRI measurements, which is a future goal.
doi:10.1016/j.schres.2010.02.333
Poster 106 HIGH RESOLUTION DEFORMATION-BASED MORPHOMETRY REVEALS A COMPLEX PATTERN OF BRAIN MORPHOLOGY CHANGES IN SCHIZOPHRENIA Tomas Kasparek1, Daniel Schwarz2, Radovan Prikryl1, Radek Marecek3, Michal Mikl3, Jiri Vanicek4, Eva Ceskova1 1 Department of Psychiatry, Faculty Hospital Brno-Bohunice and Masaryk University Brno Czech Republic; 2Institute of biostatistics and analyses Brno Czech Republic; 3Department of Neurology, Masaryk University Brno Czech Republic; 4Department of Imaging Methods Brno Czech Republic Background: Schizophrenia is linked with changes of brain morphology in gray, white matter and cerebrospinal spaces. Analysis of high-resolution deformations field have a potential to detect changes in all these three compartments. Methods: We present results of a high-resolution deformationbased morphometric study of first-episode (n = 49), chronic (n = 19) schizophrenia patients, and healthy controls (n = 127). Results: Schizophrenia subjects showed volume reduction of prefrontal lobe – both cortical and subcortical parts, cingulate gyrus, in temporal, parietal, as well as occipital lobe, in thalamus, and cerebellum. They also showed increase in of lateral ventricles, basal ganglia, and in many subarachnoidal spaces surrounding mainly frontal and temporal cortex. There were no differences between the two schizophrenia groups, in separate analysis between first-episode or chronic subjects with healthy controls analogues pattern of brain changes emerged. Discussion: Using high-resolution deformation-based morphometry it is possible to capture the complex pattern of brain morphology changes in schizophrenia. These features might be advatageous in applications that try to classify subjects with schizophrenia based on neuroimaging results.
This study was supported by a research grant from the Ministry of Health, Czech Republic No. NR 9893-4. doi:10.1016/j.schres.2010.02.334
Poster 107 LONGITUDINAL VOXEL-BASED MORPHOMETRIC STUDY TO EVALUATE PROGRESSIVE GRAY MATER CHANGES IN FIRST-EPISODE SCHIZOPHRENIA Yasuhiro Kawasaki1,2, Mikio Kido1, Tsutomu Takahashi1,2, Kazue Nakamura1, Michio Suzuki1,2 1 University of Toyama Toyama, Toyama, Japan; 2JST, CREST Tokyo, Tokyo, Japan Background: Although longitudinal magnetic resonance imaging (MRI) studies have shown that various brain regions undergo progressive tissue loss during the early phases of schizophrenia, regional pattern of these changes remain unclear. Methods: Longitudinal MRI data were obtained from 18 (12 male and 6 female) patients with first-episode schizophrenia and 20 (11 male and 9 female) healthy controls and at baseline and follow-up with mean scan interval of 2.7 years. To compare gray matter changes over time between patients and controls were evaluated with voxel-based morphometry (VBM) using SPM8 following the longitudinal DARTEL protocol. Results: In both groups of patient and control longitudinal gray mater reduction was observed in various brain regions including lateral and medial frontal regions and superior temporal region. Excessive decrease in gray matter was found in patients as compared to healthy controls in the left superior temporal region and right inferior frontal region. Discussion: Our findings suggest that there are differing longitudinal gray matter changes in patients with schizophrenia during the early phases of the illness as compared to healthy individuals. doi:10.1016/j.schres.2010.02.335
Poster 108 CONNECTION BETWEEN THE CORPUS CALLOSUM AND PREDISPOSITION TOWARDS HALLUCINATIONS – EVIDENCE FROM SCHIZOPHRENIA PATIENTS AND UNAFFECTED RELATIVES Christian Knöchel1, Viola Oertel-Knöchel1, Ralf Schönmeyer1, Anna Rotarska-Jagiela1, Vincent van de Ven2, Corinna Haenschel3, Peter Uhlhaas1, Johannes Pantel1, David E.J. Linden3 1 Frankfurt, Hessen, Germany; 2Maastricht, Netherlands, Netherlands; 3 Bangor, Bangor, Wales Background: In the current study, we applied an automatic segmentation method (Schönmeyer et al., 2007) to examine anatomical differences, as indexed by volumetry and two diffusion values (FA and MD (DTI), in the most important connection between the two hemispheres (Trepel, 1999), the corpus callosum (CC). Methods: We measured 16 chronic schizophrenia (SZ) patients, and age, gender, handedness and parental years of education matched first degree relatives and controls. Results: The results showed significant volume loss for SZ patients in the whole CC volume, as well as in the subparts posterior genu, isthmus and splenium. In addition, similar results were found for the FA values (DTI) of the whole CC, the inferior genu, the superior genu and the isthmus. However, the MD values of the whole CC and the isthmus showed increased compactness and decreased inter-
Abstracts
cellular space (Beaulieu, 2002) for SZ patients. Furthermore, the relatives had intermediate values in the volumetric and fiber integrity measurements. Discussion: In conclusion, the results conform to the hypothesis of a pathological connectivity (hypoconnectivity) between different brain regions (Friton and Frith, 1995; Friston, 1998). We provide evidences for a connection between volume loss and loss of fiber integrity in SZ patients and their unaffected relatives, which is associated with the individual psychopathology, as assessed by the PANSS (Kay et al., 1987). doi:10.1016/j.schres.2010.02.336
Poster 109 STRUCTURAL NEURAL CORRELATES OF VERBAL MEMORY IN FIRST EPISODE SCHIZOPHRENIA Martin Lepage1,2, Tom Howells1, Lisa Buchy1,2, Audrey Benoit1, Michael Bodnar1,2, Ridha Joober1,2, Ashok Malla1,2 1 Douglas Institute Verdun, Quebec, Canada; 2McGill University Montreal, Quebec, Canada Background: People with schizophrenia consistently show verbal memory impairment even in the early stages of the disease. Several studies have examined the functional neural correlates of verbal memory and have observed reduced activity in the medial temporal lobe and several areas of the prefrontal cortex, among other regions. Fewer studies however, have systematically explored structural neural correlates of verbal memory following first episode schizophrenia. We used two complementary imaging techniques, namely hippocampal volumetry and cortical thickness, to explore structural correlates of verbal memory. Methods: Sixty-five patients with a first episode of schizophrenia spectrum disorder and fifty-six healthy controls were matched on sociodemographical variables. A T1 structural MRI scan was used to perform the cortical thickness analyses and the segmentation of the hippocampus into a head, body and tail area. Multiple standardized verbal memory tests were combined into a global measure. Results: Compared to healthy controls, patients exhibited significant verbal memory impairment. Correlations between hippocampal volume and verbal memory performance revealed a significant positive association that was limited to the left hippocampal head in the healthy controls. No significant associations were observed in the patient group. The cortical thickness analyses revealed an extensive network of brain regions positively correlated with memory performance, including a large section of the left prefrontal cortex in the healthy group relative to the patient group. Discussion: These results suggest that the coupling between verbal memory and structural neural correlates is significantly reduced in first episode schizophrenia. doi:10.1016/j.schres.2010.02.337
Poster 110 ATYPICAL ANTIPSYCHOTICS: CLINICAL IMPROVEMENTS AND STRUCTURAL CEREBRAL CHANGES Genevieve Letourneau1,2,3, Emmanuel Stip1,2,3, Lahcen Ait Bentaleb1,2,3, Benjamin Stip3, Adham Mancini-Marie3, Stephane Potvin3 1 University of Montreal Montréal, QC, Canada; 2Hôpital Louis-H. Lafontaine Montréal, QC, Canada; 3Centre de recherche Fernand-Seguin Montréal, QC, Canada
229
Background: Cerebral anatomical differences have been widely described in schizophrenia patients compared to control subjects. Many studies have suggested a time-related progression of those differences, the severity of which has also been correlated with clinical characteristics of the disease. According to some recent studies, antipsychotic medications might also modulate cerebral anatomical changes in schizophrenia patients. Some results suggest a slower deterioration or even a normalization process of the cerebral structures associated with atypical antipsychotics. The present study aims to document and compare the cerebral structural effects of quetiapine and olanzapine in schizophrenia patients. Methods: We selected 29 patients suffering from schizophrenia. At the beginning of the study, 17 patients were started on a medication of olanzapine and 12 patients on a medication of quetiapine. Within the first week of the study, all patients passed a Magnetic Resonance Imaging examination, which they passed a second time at the end of the study. All analyses were made using Voxel-BasedMorphometry for Statistical Parametric Mapping (SPM)-8. Clinical status of all patients was monitored using PANSS. Results: The patients taking olanzapine took the second examination in average 4 months after the first one, while the patients taking quetiapine did so in average 5.5 months after the first one. Patients on quetiapine showed relative grey matter increases in frontal regions such as the orbitofrontal and middle frontal cortex and in the cerebellum and in cingulate regions. Patients on olanzapine showed relative grey matter increases mostly in frontal and temporal regions. Clinical differences were also noted as the quetiapine group patients had more prominent negative symptoms while the olanzapine group patients mostly displayed positive psychotic symptoms (such as hallucinations) at the beginning of the study. Both patients groups showed clinical improvement throughout the study. Discussion: Our study results confirm that treatment with atypical atypsychotics, such as Quetiapine and Olanzapine, can be associated with structural cerebral changes. Grey matter increases were mostly observed in frontal and cingulate regions, in a population of schizophrenia patients presenting mostly negative symptoms and treated with Quetiapine. These cerebral structures variations could be correlated to Negative Symptoms Scores after a treatment of Quetiapine. Grey matter increases were observed mostly in temporal and frontal regions, in a population of schizophrenia patients presenting mostly positive symptoms and treated with Olanzapine. These cerebral structures variations were significantly correlated with improvements on both positive items and global scores of PANSS evaluations after a treatment of Olanzapine. Our study results suggest that clinical improvement with atypical antipsychotics treatment could be associated with specific grey matter increases in schizophrenia patients.
doi:10.1016/j.schres.2010.02.338
Poster 111 MAGNETIC RESONANCE IMAGING OF THE SUPERIOR TEMPORAL GYRUS IN MONOZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA
Sheena Waters-Metenier1, Timothea Toulopoulou1, Alexander Sumich2, Ulrich Ettinger1,3, Robin Murray1, Marco Picchioni1,4 1 Psychological Medicine and Psychiatry, Institute of Psychiatry, KCL London United Kingdom; 2Brain Imaging and Analysis Unit, Institute of Psychiatry, KCL London United Kingdom; 3Munich Center for Neurosciences-Brain & Mind, Ludwig-Maximilians-Universität Munich Germany; 4Forensic Mental Health Science, KCL London United Kingdom