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DIFFUSION-TENSOR-TRACTOGRAPHY IN FIRST-EPISODE SCHIZOPHRENIA
Abstracts
DIFFUSION TENSOR IMAGING INVESTIGATIONS OF WHITE MATTER DEVELOPMENT IN SCHIZOPHRENIA Katherine H. Karlsgodt Department of Psychiatry, UCLA Los Angeles, California, USA Diffusion Tensor Imaging Investigations of White Matter Development in Schizophrenia Katherine H. Karlsgodt Several lines of evidence indicate that schizophrenia has a strong developmental component, with some periods of special vulnerability throughout the lifespan. One such period is in late adolescence, proximal to the period when disease onset often occurs. During this time, the brain is undergoing developmental changes even in healthy controls: there is the well known pruning of the grey matter, however there is also a simultaneous increase in white matter volume as the brain reaches its adult levels of myelination. That this phenomenon occurs so close to disease onset is of particular interest for schizophrenia, as it is often hypothesized to be a disorder of disrupted or reduced connectivity. Our group has previously shown that there are deficits in white matter integrity as measured by diffusion tensor imaging (DTI) even in the early stages of schizophrenia. Using tract-based spatial statistics (TBSS), deficits in frontal-parietal connections were shown in a sample of first-episode patients (within two years of onset). Furthermore the degree of impairment correlated with verbal working memory performance, a cognitive deficit commonly observed in schizophrenia that is known to be associated with frontal-parietal circuitry. However, though there is a growing body of work showing deficits in recentonset patients, it has been less clear whether white matter deficits exist prior to disease onset or in high-risk individuals. Moreover, whether the deficits emerge as a result of an abnormal developmental process, or from a normal process exerted on an already impaired system, has been unknown. Our recent work has assessed this using DTI in patients clinically defined as being at ultra-high risk for schizophrenia, recruited through the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Investigations, again using TBSS, in a sample spanning adolescence and early adulthood (age 12-26), indicate that there are changes in white matter integrity even before the onset of the illness. Moreover, cross-sectional analyses showed different patterns of age-related change in patients and healthy controls, with patients failing to show a normal increase of white matter integrity across adolescence in the temporal lobes. This suggests that there is a different developmental trajectory in the period just prior to disease onset, which may result in the lowered measures of white matter integrity in adult subjects and inform our understanding of how onset occurs. The same temporal lobe regions (medial temporal white matter and inferior longitudinal fasciculus) that showed a difference across age were also predictive of later social and role functioning as measured by the Global Function: Role and Global Function: Social scales. Patients with lower white matter integrity at baseline were likely to have worse functional outcome at 15 months follow up. Taken together, these findings indicate that white matter changes are present very early in the disorder and possibly pre-date the illness, that these changes may arise through a disrupted developmental process, and that they have a significant impact on subsequent levels of functioning.
111
Recent longitudinal magnetic resonance imaging studies demonstrate progressive changes in gray matter in both temporal and frontal cortices following illness onset. In contrast, far less is known about the evolution and progression of white matter abnormalities, in particular the integrity of white matter tracts that connect the frontal and the temporal lobes, tracts that have long been thought to be abnormal in schizophrenia. We here report recent findings of fronto-temporal abnormalities in first episode schizophrenia, including the uncinate fasciculus, fornix, cingulum bundle and superior longitudinal fasciculus. We also present findings in first episode patients diagnosed with schizophrenia (FESZ) and compare them to previously reported findings in patients with chronic schizophrenia. We discuss these findings in the context of white matter development, degeneration and schizophrenia related medication.
doi:10.1016/j.schres.2010.02.029
DIFFUSION-TENSOR-TRACTOGRAPHY IN FIRST-EPISODE SCHIZOPHRENIA Gary Price Institute of Neurology, University College London, London United Kingdom Abnormalities in white matter integrity may be relevant in the pathophysiology of schizophrenia. Diffusion-tensor imaging tractography has allowed white matter pathways to be studied in detail and in vivo. In this talk we will, for the most part, present our studies of the corpus callosum (CC) and uncinate fasciculus (UF) in patients with first-episode psychosis (schizophrenia and schizoaffective disorder) using a probabilistic tractography algorithm (PICo). In the study of the CC, white matter tracts crossing the splenium and genu were studied using a multi-threshold approach and multiple linear regressions were used to explore group differences. Fractional anisotropy (FA) was reduced in patients compared to controls in tracts crossing the genu, and to a lesser degree in the splenium. The study of the UF used two seed points to isolate each tract. FA and probability of connection were obtained for every voxel in both tracts. Although there were no patient-control differences in mean tract FA values, the FA distribution, as measured by the squared coefficient of variance was reduced in the left UF in the patient group: the number of voxels with high FA values in the left UF was reduced in patients. These results suggest that there are subtle structural connectivity abnormalities in white matter tracts in patients in their first-episode of psychosis that may involve aberrant connectivity in the core of these tracts.
doi:10.1016/j.schres.2010.02.030
CHANGES IN WHITE MATTER IN THE EARLY STAGES OF SCHIZOPHRENIA
Symposium 3 BRAIN ABNORMALITIES IN EMERGING PSYCHOSIS: ARE NEUROIMAGING-BASED ENDOPHENOTYPES VALID AND RELIABLE MARKERS FOR BASIC SCIENCE RESEARCH, EARLY RECOGNITION AND DISEASE PREDICTION? Co-Chairpersons: Christos Pantelis, Phillip McGuire Sunday, 11 April, 2010 - 3:30 pm - 5:30 pm
Mareck Kubicki Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Overall Abstract: The at-risk mental state for psychosis and the early phase of the disorder probably constitute the most active
doi:10.1016/j.schres.2010.02.028
DIFFUSION TENSOR IMAGING INVESTIGATIONS OF WHITE MATTER DEVELOPMENT IN SCHIZOPHRENIA Katherine H. Karlsgodt Department of Psychiatry, UCLA Los Angeles, California, USA Diffusion Tensor Imaging Investigations of White Matter Development in Schizophrenia Katherine H. Karlsgodt Several lines of evidence indicate that schizophrenia has a strong developmental component, with some periods of special vulnerability throughout the lifespan. One such period is in late adolescence, proximal to the period when disease onset often occurs. During this time, the brain is undergoing developmental changes even in healthy controls: there is the well known pruning of the grey matter, however there is also a simultaneous increase in white matter volume as the brain reaches its adult levels of myelination. That this phenomenon occurs so close to disease onset is of particular interest for schizophrenia, as it is often hypothesized to be a disorder of disrupted or reduced connectivity. Our group has previously shown that there are deficits in white matter integrity as measured by diffusion tensor imaging (DTI) even in the early stages of schizophrenia. Using tract-based spatial statistics (TBSS), deficits in frontal-parietal connections were shown in a sample of first-episode patients (within two years of onset). Furthermore the degree of impairment correlated with verbal working memory performance, a cognitive deficit commonly observed in schizophrenia that is known to be associated with frontal-parietal circuitry. However, though there is a growing body of work showing deficits in recentonset patients, it has been less clear whether white matter deficits exist prior to disease onset or in high-risk individuals. Moreover, whether the deficits emerge as a result of an abnormal developmental process, or from a normal process exerted on an already impaired system, has been unknown. Our recent work has assessed this using DTI in patients clinically defined as being at ultra-high risk for schizophrenia, recruited through the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Investigations, again using TBSS, in a sample spanning adolescence and early adulthood (age 12-26), indicate that there are changes in white matter integrity even before the onset of the illness. Moreover, cross-sectional analyses showed different patterns of age-related change in patients and healthy controls, with patients failing to show a normal increase of white matter integrity across adolescence in the temporal lobes. This suggests that there is a different developmental trajectory in the period just prior to disease onset, which may result in the lowered measures of white matter integrity in adult subjects and inform our understanding of how onset occurs. The same temporal lobe regions (medial temporal white matter and inferior longitudinal fasciculus) that showed a difference across age were also predictive of later social and role functioning as measured by the Global Function: Role and Global Function: Social scales. Patients with lower white matter integrity at baseline were likely to have worse functional outcome at 15 months follow up. Taken together, these findings indicate that white matter changes are present very early in the disorder and possibly pre-date the illness, that these changes may arise through a disrupted developmental process, and that they have a significant impact on subsequent levels of functioning.
111
Recent longitudinal magnetic resonance imaging studies demonstrate progressive changes in gray matter in both temporal and frontal cortices following illness onset. In contrast, far less is known about the evolution and progression of white matter abnormalities, in particular the integrity of white matter tracts that connect the frontal and the temporal lobes, tracts that have long been thought to be abnormal in schizophrenia. We here report recent findings of fronto-temporal abnormalities in first episode schizophrenia, including the uncinate fasciculus, fornix, cingulum bundle and superior longitudinal fasciculus. We also present findings in first episode patients diagnosed with schizophrenia (FESZ) and compare them to previously reported findings in patients with chronic schizophrenia. We discuss these findings in the context of white matter development, degeneration and schizophrenia related medication.
doi:10.1016/j.schres.2010.02.029
DIFFUSION-TENSOR-TRACTOGRAPHY IN FIRST-EPISODE SCHIZOPHRENIA Gary Price Institute of Neurology, University College London, London United Kingdom Abnormalities in white matter integrity may be relevant in the pathophysiology of schizophrenia. Diffusion-tensor imaging tractography has allowed white matter pathways to be studied in detail and in vivo. In this talk we will, for the most part, present our studies of the corpus callosum (CC) and uncinate fasciculus (UF) in patients with first-episode psychosis (schizophrenia and schizoaffective disorder) using a probabilistic tractography algorithm (PICo). In the study of the CC, white matter tracts crossing the splenium and genu were studied using a multi-threshold approach and multiple linear regressions were used to explore group differences. Fractional anisotropy (FA) was reduced in patients compared to controls in tracts crossing the genu, and to a lesser degree in the splenium. The study of the UF used two seed points to isolate each tract. FA and probability of connection were obtained for every voxel in both tracts. Although there were no patient-control differences in mean tract FA values, the FA distribution, as measured by the squared coefficient of variance was reduced in the left UF in the patient group: the number of voxels with high FA values in the left UF was reduced in patients. These results suggest that there are subtle structural connectivity abnormalities in white matter tracts in patients in their first-episode of psychosis that may involve aberrant connectivity in the core of these tracts.
doi:10.1016/j.schres.2010.02.030
CHANGES IN WHITE MATTER IN THE EARLY STAGES OF SCHIZOPHRENIA
Symposium 3 BRAIN ABNORMALITIES IN EMERGING PSYCHOSIS: ARE NEUROIMAGING-BASED ENDOPHENOTYPES VALID AND RELIABLE MARKERS FOR BASIC SCIENCE RESEARCH, EARLY RECOGNITION AND DISEASE PREDICTION? Co-Chairpersons: Christos Pantelis, Phillip McGuire Sunday, 11 April, 2010 - 3:30 pm - 5:30 pm
Mareck Kubicki Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Overall Abstract: The at-risk mental state for psychosis and the early phase of the disorder probably constitute the most active
doi:10.1016/j.schres.2010.02.028