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CINGULUM BUNDLE AND UNCINATE FASCICULUS AND THEIR INVOLVEMENT IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA: EVIDENCE FROM DIFFUSION TENSOR IMAGING AND FIBER TRACTOGRAPHY
50
SESSION XXVII
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
June 25th, 2008
White Matter Disruption in Psychosis ALTERED WHITE MATTER COMMUNICATION IN MAJOR PSYCHOSES: A POSSIBLE COMMON ENDOPHENOTYPE FOR SCHIZOPHRENIA AND BIPOLAR DISORDER?
Paolo Brambilla University of Udine and Scientific Institute IRCCS E. Medea, Udine, Italy [email protected] Major psychoses, including schizophrenia and bipolar disorder, are severe psychiatric conditions (prevalence up to 1.5% in general population), which cause high human suffering and disability. There is evidence from post-mortem and brain imaging studies that white matter communication is disrupted in both disorders. Reduced degree of myelination may play a major role in explaining imaging and neurocytochemical evidence of disrupted white matter cytoarchitecture, but the origin of such abnormalities is still largely unknown. Also, alterations of brain communication may actually be crucial in sustaining the pathophysiology and psychopathology of major psychoses, as recent investigations suggest. We here present our behavioural and MR data on cognition and function of brain connectivity in major psychoses. Particularly, evidences for abnormal brain connectivity in schizophrenia or bipolar spectrum will be debated, which may represent a common intermediate endophenotype shared by individuals susceptible to developing the disorders. The investigation of white matter pathology in schizophrenia and bipolar disorder is crucial to further understand the pathophysiology of major psychoses.
REDUCED SIZE OF THE INTERNAL CAPSULE IN SCHIZOPHRENIA: A CONTRIBUTION TO THE DYSCONNECTIVITY HYPOTHESIS
Thomas Wobrock, Peter Falkai Department of Psychiatry and Psychotherapy Georg-August-University Göttingen, Germany [email protected] Introduction: There is growing evidence for white matter abnormalities linked to the neurobiology of schizophrenia. In this respect, the anterior limb of the internal capsule (ALIC) connecting cortical and subcortical structures is involved in functional important circuits. Methods: Magnetic resonance imaging (MRI) was performed in samples of first-episode patients and members of families affected with schizophrenia (family members with schizophrenia, FM-SZ; family members not affected with schizophrenia, FM-NSZ; and healthy controls). ALIC was outlined manually following a standardized protocol. Results: Those first-episode patients with poor outcome (high increase of positive symptoms) showed a reduced maximal cross sectional area of the ALIC on the left side compared to those with good outcome, and a significant reduction of right ALIC volume in all family members (reduction of 12 - 16%) and of left ALIC volume in FM-NSZ compared to controls was detected. Additionally, both groups of family members showed a bilateral reduction in maximal cross sectional area of the ALIC. Neurocognitive performance of frontal lobe function (Subject Ordered Pointing Task) correlated negatively with the ALIC volume (r = -0.6, p = 0.01). Conclusions: Reduced white fibre structures in this area demonstrated its functional relevance by an association with reduced neurocognitive performance and an unfavourable course of the disease. In conclusion, abnormalities in ALIC can thus be taken as measure for disturbances in the frontothalamic connectivity that is discussed to be relevant for the pathophysiology of the onset and course of schizophrenia.
CINGULUM BUNDLE AND UNCINATE FASCICULUS AND THEIR INVOLVEMENT IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA: EVIDENCE FROM DIFFUSION TENSOR IMAGING AND FIBER TRACTOGRAPHY
EVIDENCE OF SHARED STRUCTURAL DYSCONNECTIVITY IN BIPOLAR DISORDER AND SCHIZOPHRENIA DETERMINED BY SHARED GENETIC FACTORS
Marek Kubicki Harvard Medical School, USA [email protected]
Andrew McIntosh, Jessika Sussmann University of Edinburgh, Edinburgh, UK [email protected]
The role of white matter abnormalities in schizophrenia has become increasingly of interest. Among all white matter fiber tracts, the frontal-temporal connections, especially those that interconnect limbic structures, are of central interest in schizophrenia. Our laboratory has diffusion tensor imaging (DTI) data that support the hypothesis that there is a relationship between abnormalities observed in cingulum bundle and uncinate fasciculus, tracts forming the limbic “belt” or “loop,” and schizophrenia symptoms and their neuropathological correlates. Here, we will present data obtained from chronic and first episode schizophrenia, as well as from schizotypal personality disorder patients, using a region of interest DTI analysis approach. We demonstrate abnormalities observed within these fiber tracts, and their differential roles in attention and memory deficits. Finally, we present preliminary data on CB and UF DTI data using fiber tractography, a relatively new and promising analytic tool for DTI, where we demonstrate increased sensitivity of this method to white matter abnormalities in schizophrenia. Using this method, we also present findings that demonstrate a relationship between these fiber tracts and some clinical and cognitive deficits observed in schizophrenia, as well as an association between tract integrity decline and age in a sample of patients diagnosed with chronic schizophrenia.
Introduction: There is strong qualitative and quantitative evidence of white matter abnormalities in schizophrenia and bipolar disorder from structural magnetic resonance imaging (MRI). There is also good evidence of altered connectivity in schizophrenia using diffusion tensor magnetic resonance imaging, but no study has yet addressed the diagnostic specificity of these findings or whether they are related to specific suscepatbility genes. Methods: Diffusion tensor MRI was used to assess white matter integrity in patients with bipolar I disorder (BD) (n=42), schizophrenia (n=28) and healthy controls (n=38). Clinically stable patients with one other close family member with the same diagnosis were selected. In a second study, we examined white matter associations with Neuregulin I in a sample of healthy controls. Fractional anisotropy (FA) was compared between the groups using voxel-based morphometry and automated region of interest analysis. Results: Patients with BD and those with schizophrenia showed reduced FA in the anterior limb of the internal capsule and uncinate fasciculus compared with controls. Results from the second study showed reductions in those carrying a Neuregulin 1 variant previously associated with psychotic symtpoms. Conclusions: Reduced white matter density and integrity in the internal capsule and uncinate fasciculus region is common to both schizophrenia and BD. It is likely that this shared white matter dysruption is determiend by shared genetic risk factors. Acknowledgements: We would like to thank all of the participants for taking part and the Chief Scientist’s Office and Health Foundation for supporting our work.
SESSION XXVII
Abstracts / Schizophrenia Research 102/1–3, Supplement 2 (2008) 1–279
June 25th, 2008
White Matter Disruption in Psychosis ALTERED WHITE MATTER COMMUNICATION IN MAJOR PSYCHOSES: A POSSIBLE COMMON ENDOPHENOTYPE FOR SCHIZOPHRENIA AND BIPOLAR DISORDER?
Paolo Brambilla University of Udine and Scientific Institute IRCCS E. Medea, Udine, Italy [email protected] Major psychoses, including schizophrenia and bipolar disorder, are severe psychiatric conditions (prevalence up to 1.5% in general population), which cause high human suffering and disability. There is evidence from post-mortem and brain imaging studies that white matter communication is disrupted in both disorders. Reduced degree of myelination may play a major role in explaining imaging and neurocytochemical evidence of disrupted white matter cytoarchitecture, but the origin of such abnormalities is still largely unknown. Also, alterations of brain communication may actually be crucial in sustaining the pathophysiology and psychopathology of major psychoses, as recent investigations suggest. We here present our behavioural and MR data on cognition and function of brain connectivity in major psychoses. Particularly, evidences for abnormal brain connectivity in schizophrenia or bipolar spectrum will be debated, which may represent a common intermediate endophenotype shared by individuals susceptible to developing the disorders. The investigation of white matter pathology in schizophrenia and bipolar disorder is crucial to further understand the pathophysiology of major psychoses.
REDUCED SIZE OF THE INTERNAL CAPSULE IN SCHIZOPHRENIA: A CONTRIBUTION TO THE DYSCONNECTIVITY HYPOTHESIS
Thomas Wobrock, Peter Falkai Department of Psychiatry and Psychotherapy Georg-August-University Göttingen, Germany [email protected] Introduction: There is growing evidence for white matter abnormalities linked to the neurobiology of schizophrenia. In this respect, the anterior limb of the internal capsule (ALIC) connecting cortical and subcortical structures is involved in functional important circuits. Methods: Magnetic resonance imaging (MRI) was performed in samples of first-episode patients and members of families affected with schizophrenia (family members with schizophrenia, FM-SZ; family members not affected with schizophrenia, FM-NSZ; and healthy controls). ALIC was outlined manually following a standardized protocol. Results: Those first-episode patients with poor outcome (high increase of positive symptoms) showed a reduced maximal cross sectional area of the ALIC on the left side compared to those with good outcome, and a significant reduction of right ALIC volume in all family members (reduction of 12 - 16%) and of left ALIC volume in FM-NSZ compared to controls was detected. Additionally, both groups of family members showed a bilateral reduction in maximal cross sectional area of the ALIC. Neurocognitive performance of frontal lobe function (Subject Ordered Pointing Task) correlated negatively with the ALIC volume (r = -0.6, p = 0.01). Conclusions: Reduced white fibre structures in this area demonstrated its functional relevance by an association with reduced neurocognitive performance and an unfavourable course of the disease. In conclusion, abnormalities in ALIC can thus be taken as measure for disturbances in the frontothalamic connectivity that is discussed to be relevant for the pathophysiology of the onset and course of schizophrenia.
CINGULUM BUNDLE AND UNCINATE FASCICULUS AND THEIR INVOLVEMENT IN THE NEUROPATHOLOGY OF SCHIZOPHRENIA: EVIDENCE FROM DIFFUSION TENSOR IMAGING AND FIBER TRACTOGRAPHY
EVIDENCE OF SHARED STRUCTURAL DYSCONNECTIVITY IN BIPOLAR DISORDER AND SCHIZOPHRENIA DETERMINED BY SHARED GENETIC FACTORS
Marek Kubicki Harvard Medical School, USA [email protected]
Andrew McIntosh, Jessika Sussmann University of Edinburgh, Edinburgh, UK [email protected]
The role of white matter abnormalities in schizophrenia has become increasingly of interest. Among all white matter fiber tracts, the frontal-temporal connections, especially those that interconnect limbic structures, are of central interest in schizophrenia. Our laboratory has diffusion tensor imaging (DTI) data that support the hypothesis that there is a relationship between abnormalities observed in cingulum bundle and uncinate fasciculus, tracts forming the limbic “belt” or “loop,” and schizophrenia symptoms and their neuropathological correlates. Here, we will present data obtained from chronic and first episode schizophrenia, as well as from schizotypal personality disorder patients, using a region of interest DTI analysis approach. We demonstrate abnormalities observed within these fiber tracts, and their differential roles in attention and memory deficits. Finally, we present preliminary data on CB and UF DTI data using fiber tractography, a relatively new and promising analytic tool for DTI, where we demonstrate increased sensitivity of this method to white matter abnormalities in schizophrenia. Using this method, we also present findings that demonstrate a relationship between these fiber tracts and some clinical and cognitive deficits observed in schizophrenia, as well as an association between tract integrity decline and age in a sample of patients diagnosed with chronic schizophrenia.
Introduction: There is strong qualitative and quantitative evidence of white matter abnormalities in schizophrenia and bipolar disorder from structural magnetic resonance imaging (MRI). There is also good evidence of altered connectivity in schizophrenia using diffusion tensor magnetic resonance imaging, but no study has yet addressed the diagnostic specificity of these findings or whether they are related to specific suscepatbility genes. Methods: Diffusion tensor MRI was used to assess white matter integrity in patients with bipolar I disorder (BD) (n=42), schizophrenia (n=28) and healthy controls (n=38). Clinically stable patients with one other close family member with the same diagnosis were selected. In a second study, we examined white matter associations with Neuregulin I in a sample of healthy controls. Fractional anisotropy (FA) was compared between the groups using voxel-based morphometry and automated region of interest analysis. Results: Patients with BD and those with schizophrenia showed reduced FA in the anterior limb of the internal capsule and uncinate fasciculus compared with controls. Results from the second study showed reductions in those carrying a Neuregulin 1 variant previously associated with psychotic symtpoms. Conclusions: Reduced white matter density and integrity in the internal capsule and uncinate fasciculus region is common to both schizophrenia and BD. It is likely that this shared white matter dysruption is determiend by shared genetic risk factors. Acknowledgements: We would like to thank all of the participants for taking part and the Chief Scientist’s Office and Health Foundation for supporting our work.