- Email: [email protected]
EXPLORING THE NEURAL SUBSTRATE OF THE VULNERABILITY TO FIRST EPISODE PSYCHOSIS USING fMRI
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Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
DISRUPTION OF WHITE MATTER INTEGRITY IN THE INFERIOR LONGITUDINAL FASCICULUS IN ADOLESCENTS WITH SCHIZOPHRENIA AS REVEALED BY FIBER TRACTOGRAPHY
Sanjiv Kumra University of Minnesota, Minneapolis, MN, USA [email protected] Introduction: There is increasing evidence that schizophrenia is characterized by abnormalities in white matter. The authors investigated the integrity of white matter tracts in adolescents with schizophrenia. Methods: Cross-sectional, case-control, whole-brain, voxel-based analysis and fiber tractography using diffusion tensor magnetic resonance imaging conducted at a university research institute. Forty-four individuals (age range, 11-18 years), 23 with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 21 demographically similar healthy controls participated in the study. Results: Voxelwise analysis revealed that adolescents with schizophrenia had reduced fractional anisotropy within the left inferior temporal (P < 0.001) and occipital (P < 0.001) regions. Tractography was performed to extract the left and the right inferior longitudinal fasciculi (ILF). Measuring the mean diffusion indices along the left ILF, patients had significantly reduced fractional anis otropy (P < 0.001) as well as significantly increased radial diffusivity (P < 0.001) and trace (P = 0.003) after adjusting for differences in a measure thought to reflect premorbid intelligence, Wide Range Achievement Test 3 reading scores. Exploratory analyses revealed that patients with a history of visual hallucinations had lower fractional anisotropy in the left ILF (P = 0.02) than patients without visual hallucinations. Conclusions: Our findings, which benefited from greater image resolution and methodological control than previous studies conducted in adolescents with schizophrenia, provide strong evidence for lower white matter integrity in the left ILF, particularly for patients with a history of visual hallucinations. References [1] Ashtari M, Cottone J, Ardekani BA, Cervellione K, et al. Disruption of white matter integrity in the inferior longitudinal fasciculus in adolescents with schizophrenia as revealed by fiber tractography. Arch Gen Psychiatry. 2007 Nov;64(11):1270-80.
FIBER-BASED ANALYSIS OF DIFFUSION TENSOR IMAGING AND MAGNETIZATION TRANSFER RATIO SCANS IN SCHIZOPHRENIA
Rene Mandl, Hugo Schnack, Martijn van den Heuvel, Rehana de Vries, Judy Luigjes, Wiepke Cahn, René Kahn, Hilleke Hulshoff Pol University Medical Center Utrecht, Utrecht, The Netherlands [email protected] Introduction: Using diffusion tensor imaging (DTI) altered fractional anisotropy (FA) was shown in fibers connecting the prefontal and temporal lobes in schizophrenia. Contributions of altered myelin, measured using magnetic transfer ratio (MTR) imaging, have been suggested in chronically ill patients. However, the extent to which white matter is aberrant in the early stages of schizophrenia is unknown. Methods: DTI and MTR images were acquired with a 1.5T scanner in 40 patients with schizophrenia and compared to 40 healthy comparison subjects. Seven fiber bundles of interest were selected based on their connections to gray matter areas found earlier to be significantly decreased in density in patients. The spinothalamic tract, genu of the corpus callosum, middle cerebellar peduncle, pyramidal tract, inferior longitudinal fasciculus and uncinate fasciculus (UF) were traced and averaged for each individual subject and transformed into standard space. Results: Increased MTR signal was found in the right UF in patients as compared to controls. No changes in FA were found in the UF. No MTR or FA changes were found in other selected fibers. Higher MTR in the right UF correlated negatively with level of education (r=-0.45, p<0.001, n=79). Higher MTR in the left UF correlated negatively with severity of negative symptoms (r=-0.39, p=0.01, n=40).
Conclusions: Increased myelination of the UF suggests increased communication speed between the anterior temporal and inferior frontal cortices in patients. This finding suggests altered levels of communication between the right frontal and temporal cortices in schizophrenia. EXPLORING THE NEURAL SUBSTRATE OF THE VULNERABILITY TO FIRST EPISODE PSYCHOSIS USING fMRI
Marco Picchioni, Mathew Broome, Sara Weinstein, Pall Matthiason, Philip McGuire Institute of Psychiatry, London, UK [email protected] Introduction: The neural substrate of the vulnerability to the first break of psychosis is unknown. Object working memory task performance may discriminate between the early stages of schizophrenia. Such tasks reliably recruit frontal and temporal cortices, possible sites of progressive volume change over the early course of the disorder. We wanted to clarify if functional changes can be detected in the early stages of schizophrenia, and to identify both their anatomical location and relationship to the stage of illness using an object working memory task in which the length of memory delay was manipulated. Methods: 40 subjects contributed: 10 first episode psychosis (FEp) patients, 16 with an at risk mental state (ARMS) and 14 healthy controls. We collected functional MRI data while the subjects performed a modified version of the delayed matching to sample (D MTS) task from the Cambridge Automated Neuropsychological Test Battery. Results: The two patient groups making a greater number of errors at longer memory delays. At successful recognition a main effects of group was detected in the medial temporal lobe bilaterally, while a main effect of delay was detected in the left medial temporal lobe. At each length of memory delay the patient groups showed greater activation of medial temporal regions when performing the task accurately. Conclusions: Both ARMS & FEp groups showed greater activation than controls in the medial temporal cortex across all lengths of memory delay. These differences were not related to poorer task performance, but suggest an inefficiency or compensatory mechanism that may correlate with the vulnerability to psychosis. References [1] Picchioni MM., Matthiasson P, Broome M, Giampietro V, Brammer M, Williams S, McGuire PK. Increased activation of temporal but not prefrontal cortex with increasing duration of mnemonic delay during an object working memory task. Human Brain Mapping. 2007; 28: 1235-1250. WHERE DO AUDITORY HALLUCINATIONS COME FROM? RIGHT SUPERIOR TEMPORAL SULCUS AND SPATIAL LOCATION OF AUDITORY HALLUCINATIONS
Marion Plaze 1 , Marie-Laure Paillère-Martinot 2 , Jani Penttilä 2 , Dominique Januel 3 , Renaud de Beaurepair 4 , Franck Bellivier 5 , Jamila Andoh 2 , André Galinowski 6 , Eric Artiges 2 , Jean-Pierre Olié 6 , Jean-François Mangin 7 , Jean-Luc Martinot 2 , Pamela Butler 8 1 INSERM-CEA U797 - Sainte Anne Hospital, Psychiatry Department (SHU), Orsay - Paris; 2 INSERM-CEA U797, Orsay, France; 3 Romain Roland Hospital, Department 3 (area 93G03) - CHS Ville-Evrard, Romain Roland Hospital, Dept; 4 Paul Guiraud Hospital, Psychiatry Department 4 (area 94G11), Villejuif, France; 5 Département de Psychiatrie, Hôpital Chenevier-Mondor, Université Paris XII, Paris, Créteil; 6 Sainte Anne Hospital, Psychiatry Department (SHU), Paris; 7 CEA/DSV/I2BM/LNAO, Paris, France; 8 Nathan Kline Institute, Orangeburg, New York Email: [email protected] Introduction: Schizophrenia patients perceive their auditory-verbal hallucinations (AH) as coming either from outside (external-AH) or
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
DISRUPTION OF WHITE MATTER INTEGRITY IN THE INFERIOR LONGITUDINAL FASCICULUS IN ADOLESCENTS WITH SCHIZOPHRENIA AS REVEALED BY FIBER TRACTOGRAPHY
Sanjiv Kumra University of Minnesota, Minneapolis, MN, USA [email protected] Introduction: There is increasing evidence that schizophrenia is characterized by abnormalities in white matter. The authors investigated the integrity of white matter tracts in adolescents with schizophrenia. Methods: Cross-sectional, case-control, whole-brain, voxel-based analysis and fiber tractography using diffusion tensor magnetic resonance imaging conducted at a university research institute. Forty-four individuals (age range, 11-18 years), 23 with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 21 demographically similar healthy controls participated in the study. Results: Voxelwise analysis revealed that adolescents with schizophrenia had reduced fractional anisotropy within the left inferior temporal (P < 0.001) and occipital (P < 0.001) regions. Tractography was performed to extract the left and the right inferior longitudinal fasciculi (ILF). Measuring the mean diffusion indices along the left ILF, patients had significantly reduced fractional anis otropy (P < 0.001) as well as significantly increased radial diffusivity (P < 0.001) and trace (P = 0.003) after adjusting for differences in a measure thought to reflect premorbid intelligence, Wide Range Achievement Test 3 reading scores. Exploratory analyses revealed that patients with a history of visual hallucinations had lower fractional anisotropy in the left ILF (P = 0.02) than patients without visual hallucinations. Conclusions: Our findings, which benefited from greater image resolution and methodological control than previous studies conducted in adolescents with schizophrenia, provide strong evidence for lower white matter integrity in the left ILF, particularly for patients with a history of visual hallucinations. References [1] Ashtari M, Cottone J, Ardekani BA, Cervellione K, et al. Disruption of white matter integrity in the inferior longitudinal fasciculus in adolescents with schizophrenia as revealed by fiber tractography. Arch Gen Psychiatry. 2007 Nov;64(11):1270-80.
FIBER-BASED ANALYSIS OF DIFFUSION TENSOR IMAGING AND MAGNETIZATION TRANSFER RATIO SCANS IN SCHIZOPHRENIA
Rene Mandl, Hugo Schnack, Martijn van den Heuvel, Rehana de Vries, Judy Luigjes, Wiepke Cahn, René Kahn, Hilleke Hulshoff Pol University Medical Center Utrecht, Utrecht, The Netherlands [email protected] Introduction: Using diffusion tensor imaging (DTI) altered fractional anisotropy (FA) was shown in fibers connecting the prefontal and temporal lobes in schizophrenia. Contributions of altered myelin, measured using magnetic transfer ratio (MTR) imaging, have been suggested in chronically ill patients. However, the extent to which white matter is aberrant in the early stages of schizophrenia is unknown. Methods: DTI and MTR images were acquired with a 1.5T scanner in 40 patients with schizophrenia and compared to 40 healthy comparison subjects. Seven fiber bundles of interest were selected based on their connections to gray matter areas found earlier to be significantly decreased in density in patients. The spinothalamic tract, genu of the corpus callosum, middle cerebellar peduncle, pyramidal tract, inferior longitudinal fasciculus and uncinate fasciculus (UF) were traced and averaged for each individual subject and transformed into standard space. Results: Increased MTR signal was found in the right UF in patients as compared to controls. No changes in FA were found in the UF. No MTR or FA changes were found in other selected fibers. Higher MTR in the right UF correlated negatively with level of education (r=-0.45, p<0.001, n=79). Higher MTR in the left UF correlated negatively with severity of negative symptoms (r=-0.39, p=0.01, n=40).
Conclusions: Increased myelination of the UF suggests increased communication speed between the anterior temporal and inferior frontal cortices in patients. This finding suggests altered levels of communication between the right frontal and temporal cortices in schizophrenia. EXPLORING THE NEURAL SUBSTRATE OF THE VULNERABILITY TO FIRST EPISODE PSYCHOSIS USING fMRI
Marco Picchioni, Mathew Broome, Sara Weinstein, Pall Matthiason, Philip McGuire Institute of Psychiatry, London, UK [email protected] Introduction: The neural substrate of the vulnerability to the first break of psychosis is unknown. Object working memory task performance may discriminate between the early stages of schizophrenia. Such tasks reliably recruit frontal and temporal cortices, possible sites of progressive volume change over the early course of the disorder. We wanted to clarify if functional changes can be detected in the early stages of schizophrenia, and to identify both their anatomical location and relationship to the stage of illness using an object working memory task in which the length of memory delay was manipulated. Methods: 40 subjects contributed: 10 first episode psychosis (FEp) patients, 16 with an at risk mental state (ARMS) and 14 healthy controls. We collected functional MRI data while the subjects performed a modified version of the delayed matching to sample (D MTS) task from the Cambridge Automated Neuropsychological Test Battery. Results: The two patient groups making a greater number of errors at longer memory delays. At successful recognition a main effects of group was detected in the medial temporal lobe bilaterally, while a main effect of delay was detected in the left medial temporal lobe. At each length of memory delay the patient groups showed greater activation of medial temporal regions when performing the task accurately. Conclusions: Both ARMS & FEp groups showed greater activation than controls in the medial temporal cortex across all lengths of memory delay. These differences were not related to poorer task performance, but suggest an inefficiency or compensatory mechanism that may correlate with the vulnerability to psychosis. References [1] Picchioni MM., Matthiasson P, Broome M, Giampietro V, Brammer M, Williams S, McGuire PK. Increased activation of temporal but not prefrontal cortex with increasing duration of mnemonic delay during an object working memory task. Human Brain Mapping. 2007; 28: 1235-1250. WHERE DO AUDITORY HALLUCINATIONS COME FROM? RIGHT SUPERIOR TEMPORAL SULCUS AND SPATIAL LOCATION OF AUDITORY HALLUCINATIONS
Marion Plaze 1 , Marie-Laure Paillère-Martinot 2 , Jani Penttilä 2 , Dominique Januel 3 , Renaud de Beaurepair 4 , Franck Bellivier 5 , Jamila Andoh 2 , André Galinowski 6 , Eric Artiges 2 , Jean-Pierre Olié 6 , Jean-François Mangin 7 , Jean-Luc Martinot 2 , Pamela Butler 8 1 INSERM-CEA U797 - Sainte Anne Hospital, Psychiatry Department (SHU), Orsay - Paris; 2 INSERM-CEA U797, Orsay, France; 3 Romain Roland Hospital, Department 3 (area 93G03) - CHS Ville-Evrard, Romain Roland Hospital, Dept; 4 Paul Guiraud Hospital, Psychiatry Department 4 (area 94G11), Villejuif, France; 5 Département de Psychiatrie, Hôpital Chenevier-Mondor, Université Paris XII, Paris, Créteil; 6 Sainte Anne Hospital, Psychiatry Department (SHU), Paris; 7 CEA/DSV/I2BM/LNAO, Paris, France; 8 Nathan Kline Institute, Orangeburg, New York Email: [email protected] Introduction: Schizophrenia patients perceive their auditory-verbal hallucinations (AH) as coming either from outside (external-AH) or