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MAGNETIC RESONANCE IMAGING OF THE SUPERIOR TEMPORAL GYRUS IN MONOZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA
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
230
Abstracts
Background: Volumetric MRI abnormalities of the superior temporal gyrus (STG) and substructures are well established in firstepisode (Sumich et al., 2002, Molina et al., 2006, Kuroki et al., 2006) and chronic schizophrenia (Sun et al., 2009, Honea et al., 2005) and have been associated with positive psychotic symptoms, including auditory hallucinations (Barta et al., 1990, Garcia-Marti et al., 2008, Marti-Bonmati et al., 2007, Takahashi et al., 2006, Sumich et al., 2005), delusions (Menon et al., 1995, Takahashi et al., 2006, Sumich et al., 2005), and thought disorder (Vita et al., 1995, Menon et al., 1995, Shenton et al., 1992), as well as negative symptoms (Anderson et al., 2002). Although the heritability of the STG has been shown to be high (Hulshoff Pol et al., 2006) and STG abnormalities have been identified in first-degree relatives (Goghari et al., 2007a, Goghari et al., 2007b) and offspring (Rajarethinam et al., 2004), it is unknown to what degree these abnormalities are manifested in unaffected co-twins of schizophrenia patients. No stereological region of interest (ROI) study has yet investigated the degree of these abnormalities in monozygotic (MZ) twins from concordant and discordant pairs. Methods: We employed a twin study design, consisting of 134 MZ twins, including 21 pairs concordant for schizophrenia, 18 pairs discordant for schizophrenia, and 27 pairs of healthy control twins. Groups were matched for age, sex, handedness, level of education, parental socioeconomical status, and ethnicity. The volume of the whole superior temporal gyrus (gray and white matter) was measured in cubic centimeters on the basis of stereologic principles implemented in PC-based software MEASURE (Barta et al., 1997) by a single rater without knowledge of subject group or twin pair status. The anatomic boundaries of the STG were determined in accordance with a previously described protocol (Frangou et al., 1997) augmented by reference to additional neuroanatomical atlases. Results: Patients with schizophrenia from MZ concordant and MZ discordant pairs exhibited significantly reduced total STG volumes compared to controls (t= −3.17, p = 0.002 and t = −2.54, p = 0.014, respectively), even after covarying for age, sex, site of imaging, and whole brain volume. STG volumes of patients with schizophrenia did not differ whether they came from MZ concordant or discordant pairs. There was a non-significant trend for the well co-twins from MZ discordant pairs to show reduced STG volumes relative to the controls (t= −1.83, p = 0.072), although they did not differ significantly from their ill co-twins. Discussion: To our knowledge, this is the first ROI study that has investigated volumetric deficits in the STG of MZ twins concordant and discordant for schizophrenia. These preliminary results confirm that STG volume is compromised in schizophrenia and may reflect, in part, the influence of genetic factors.
representations (hallucinations). The brain reward system is normally activated by salient events. Recently it was reported that unlike healthy controls, patients show activity in reward related brain areas to neutral stimuli, suggesting a dysfunction of the brain reward system in schizophrenic patients. Other studies have shown that schizophrenic patients have less activation in the reward system during the outcome phase. So far, only a few studies have examined the function of the brain reward system in antipsychotic naïve schizophrenic patients, and to our knowledge there are no longitudinal studies on this group of patients. The aim of the current study is to investigate the brain reward system in antipsychotic naïve schizophrenic patients before and after a treatment period of 6 weeks with amisulpride (D2 antagonist, atypical antipsychotic). Methods: The study has currently included 16 antipsychotic-naïve patients with schizophrenia and 16 age and gender matched healthy controls. All participants have been assessed with an fMRI reward paradigm using a variant of the Monetary Incentive Delay task. Data were analysed in Brainvoyager using general linear model. Patients have further been rated on the PANSS scale regarding their psychopathology, and we have measured their subjective well-being, their level of function and their side-effects before and after medical treatment. Results: Only baseline data will be presented in this preliminary report. During the anticipation phase the antipsychotic naïve schizophrenic patients showed a significantly smaller BOLD response of the ventral striatum compared to the healthy controls. In the healthy controls a significant higher BOLD response was found in the ventral striatum following salient than following neutral stimuli, but this difference was not found in the patients. Discussion: Although our results are still preliminary, they are in line with earlier studies on medication free schizophrenic patients, in which a reduced difference was found between striatal activity elicited by salient and neutral events in the schizophrenic patients compared to healthy controls. Since a few studies have found an increased striatal activity related to neutral events, we expected to find that the reduced difference was caused by an increased BOLD response during the neutral events. However, our data suggest that there is an overall reduced increase in the striatal BOLD response of the schizophrenic patients regardless of which cue is presented. How does this fit the dopamine hypothesis, suggesting an overall increased activity in striatum? A possible explanation could be that a permanent hyperactivity in this network in the psychotic patients makes the network unable to respond properly to relevant (salient) stimuli because of a continuously high level of activity. We plan to perform further analyses looking into the activation of the outcome phase and we will investigate how the fMRI results correlate to the psychopathological measures.
doi:10.1016/j.schres.2010.02.339
doi:10.1016/j.schres.2010.02.340
Poster 112
Poster 113
PECANS –PAN EUROPEAN COLLABORATION ON ANTIPSYCHOTIC NAïVE SCHIZOPHRENIA: PRELIMINARY RESULTS ON THE FMRI REWARD PARADIGM
THE NEURAL BASIS OF SELF-REFLECTIVE PROCESSING IN SCHIZOPHRENIA PATIENTS: AN FMRI STUDY
1,3
2
1,3
Mette Odegaard Nielsen , Egill Rostrup , Birte Glenthoj Center for Neuropsychiatric Schizophrenia Research Glostrup Denmark; 2 Functional Imaging Unit Glostrup Denmark; 3Copenhagen University Copenhagen Denmark
1
Background: The salience hypothesis suggest, that in schizophrenia a dysregulated dopamine transmission distorts the normal process of contextually driven salience attribution, which leads to aberrant assignment of salience to external objects (delusions) and internal
Lisette van der Meer1, Marieke Pijnenborg1,2, Willem Nolen3, Rikus Knegtering4, Andre Aleman1 1 BCN-NIC, Department of Neuroscience, University Medical Center Groningen Groningen Netherlands; 2Department of Psychotic Disorders, GGZ-Drenthe Assen Netherlands; 3Department of Psychiatry, University Medical Center Gronigen Groningen Netherlands; 4Department of Psychotic Disorders, Lentis Groningen Groningen Netherlands Background: Many studies have investigated the neural basis of deviant social cognitive processing in patients with schizophrenia.
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
230
Abstracts
Background: Volumetric MRI abnormalities of the superior temporal gyrus (STG) and substructures are well established in firstepisode (Sumich et al., 2002, Molina et al., 2006, Kuroki et al., 2006) and chronic schizophrenia (Sun et al., 2009, Honea et al., 2005) and have been associated with positive psychotic symptoms, including auditory hallucinations (Barta et al., 1990, Garcia-Marti et al., 2008, Marti-Bonmati et al., 2007, Takahashi et al., 2006, Sumich et al., 2005), delusions (Menon et al., 1995, Takahashi et al., 2006, Sumich et al., 2005), and thought disorder (Vita et al., 1995, Menon et al., 1995, Shenton et al., 1992), as well as negative symptoms (Anderson et al., 2002). Although the heritability of the STG has been shown to be high (Hulshoff Pol et al., 2006) and STG abnormalities have been identified in first-degree relatives (Goghari et al., 2007a, Goghari et al., 2007b) and offspring (Rajarethinam et al., 2004), it is unknown to what degree these abnormalities are manifested in unaffected co-twins of schizophrenia patients. No stereological region of interest (ROI) study has yet investigated the degree of these abnormalities in monozygotic (MZ) twins from concordant and discordant pairs. Methods: We employed a twin study design, consisting of 134 MZ twins, including 21 pairs concordant for schizophrenia, 18 pairs discordant for schizophrenia, and 27 pairs of healthy control twins. Groups were matched for age, sex, handedness, level of education, parental socioeconomical status, and ethnicity. The volume of the whole superior temporal gyrus (gray and white matter) was measured in cubic centimeters on the basis of stereologic principles implemented in PC-based software MEASURE (Barta et al., 1997) by a single rater without knowledge of subject group or twin pair status. The anatomic boundaries of the STG were determined in accordance with a previously described protocol (Frangou et al., 1997) augmented by reference to additional neuroanatomical atlases. Results: Patients with schizophrenia from MZ concordant and MZ discordant pairs exhibited significantly reduced total STG volumes compared to controls (t= −3.17, p = 0.002 and t = −2.54, p = 0.014, respectively), even after covarying for age, sex, site of imaging, and whole brain volume. STG volumes of patients with schizophrenia did not differ whether they came from MZ concordant or discordant pairs. There was a non-significant trend for the well co-twins from MZ discordant pairs to show reduced STG volumes relative to the controls (t= −1.83, p = 0.072), although they did not differ significantly from their ill co-twins. Discussion: To our knowledge, this is the first ROI study that has investigated volumetric deficits in the STG of MZ twins concordant and discordant for schizophrenia. These preliminary results confirm that STG volume is compromised in schizophrenia and may reflect, in part, the influence of genetic factors.
representations (hallucinations). The brain reward system is normally activated by salient events. Recently it was reported that unlike healthy controls, patients show activity in reward related brain areas to neutral stimuli, suggesting a dysfunction of the brain reward system in schizophrenic patients. Other studies have shown that schizophrenic patients have less activation in the reward system during the outcome phase. So far, only a few studies have examined the function of the brain reward system in antipsychotic naïve schizophrenic patients, and to our knowledge there are no longitudinal studies on this group of patients. The aim of the current study is to investigate the brain reward system in antipsychotic naïve schizophrenic patients before and after a treatment period of 6 weeks with amisulpride (D2 antagonist, atypical antipsychotic). Methods: The study has currently included 16 antipsychotic-naïve patients with schizophrenia and 16 age and gender matched healthy controls. All participants have been assessed with an fMRI reward paradigm using a variant of the Monetary Incentive Delay task. Data were analysed in Brainvoyager using general linear model. Patients have further been rated on the PANSS scale regarding their psychopathology, and we have measured their subjective well-being, their level of function and their side-effects before and after medical treatment. Results: Only baseline data will be presented in this preliminary report. During the anticipation phase the antipsychotic naïve schizophrenic patients showed a significantly smaller BOLD response of the ventral striatum compared to the healthy controls. In the healthy controls a significant higher BOLD response was found in the ventral striatum following salient than following neutral stimuli, but this difference was not found in the patients. Discussion: Although our results are still preliminary, they are in line with earlier studies on medication free schizophrenic patients, in which a reduced difference was found between striatal activity elicited by salient and neutral events in the schizophrenic patients compared to healthy controls. Since a few studies have found an increased striatal activity related to neutral events, we expected to find that the reduced difference was caused by an increased BOLD response during the neutral events. However, our data suggest that there is an overall reduced increase in the striatal BOLD response of the schizophrenic patients regardless of which cue is presented. How does this fit the dopamine hypothesis, suggesting an overall increased activity in striatum? A possible explanation could be that a permanent hyperactivity in this network in the psychotic patients makes the network unable to respond properly to relevant (salient) stimuli because of a continuously high level of activity. We plan to perform further analyses looking into the activation of the outcome phase and we will investigate how the fMRI results correlate to the psychopathological measures.
doi:10.1016/j.schres.2010.02.339
doi:10.1016/j.schres.2010.02.340
Poster 112
Poster 113
PECANS –PAN EUROPEAN COLLABORATION ON ANTIPSYCHOTIC NAïVE SCHIZOPHRENIA: PRELIMINARY RESULTS ON THE FMRI REWARD PARADIGM
THE NEURAL BASIS OF SELF-REFLECTIVE PROCESSING IN SCHIZOPHRENIA PATIENTS: AN FMRI STUDY
1,3
2
1,3
Mette Odegaard Nielsen , Egill Rostrup , Birte Glenthoj Center for Neuropsychiatric Schizophrenia Research Glostrup Denmark; 2 Functional Imaging Unit Glostrup Denmark; 3Copenhagen University Copenhagen Denmark
1
Background: The salience hypothesis suggest, that in schizophrenia a dysregulated dopamine transmission distorts the normal process of contextually driven salience attribution, which leads to aberrant assignment of salience to external objects (delusions) and internal
Lisette van der Meer1, Marieke Pijnenborg1,2, Willem Nolen3, Rikus Knegtering4, Andre Aleman1 1 BCN-NIC, Department of Neuroscience, University Medical Center Groningen Groningen Netherlands; 2Department of Psychotic Disorders, GGZ-Drenthe Assen Netherlands; 3Department of Psychiatry, University Medical Center Gronigen Groningen Netherlands; 4Department of Psychotic Disorders, Lentis Groningen Groningen Netherlands Background: Many studies have investigated the neural basis of deviant social cognitive processing in patients with schizophrenia.