White Matter Tractography in Bipolar Disorder and Schizophrenia

Division of Psychiatry, University of Edinburgh, Edinburgh United Kingdom.
Biological psychiatry (Impact Factor: 10.26). 10/2008; 64(12):1088-92. DOI: 10.1016/j.biopsych.2008.07.026
Source: PubMed


Abnormalities of white matter integrity have been repeatedly demonstrated in both schizophrenia and bipolar disorder with voxel based methods. Because these methods are limited in their ability to localize deficits to specific tracts, we sought to investigate alterations in fractional anisotropy (FA) in the uncinate fasciculus and anterior thalamic radiation with probabilistic tractography.
Individuals with schizophrenia (n = 25) or bipolar disorder (n = 40) were recruited from families with two or more affected members and age-matched to a control group (n = 49). All participants underwent diffusion tensor magnetic resonance imaging that was subsequently analyzed with probabilistic tractography. Mean FA was calculated bilaterally for the uncinate and anterior thalamic radiation and compared between groups with repeated measures analysis of variance.
Patients with schizophrenia or bipolar disorder showed common reductions in the uncinate fasciculus and anterior thalamic radiation. These reductions were unrelated to age, duration of illness, current medication, or current psychiatric symptoms in all patients or the lifetime presence of psychotic symptoms in bipolar subjects.
Patients with schizophrenia or bipolar disorder show common abnormalities in the uncinate fasciculus and anterior thalamic radiation that fail to respect traditional diagnostic boundaries. These deficits might be related to shared risk factors and disease mechanisms common to both disorders.

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    • "Diffusion MRI data, jointly with deterministic, and more recently, probabilistic tractography methods (Mukherjee et al., 2008) have been used successfully during the last decade in inferring brain connectivity networks at the granularity of individual voxels or larger ROIs (Hagmann et al., 2007). Various structural properties of these networks have been discovered for the healthy brain and for various psychiatric diseases (Daianu et al., 2013; McIntosh et al., 2008). When combined with fMRI and behavioral or genomic analysis, these non-trivial topological properties provide new insights about the role of individual ROIs in specific networks and the way in which these distinct ROIs exchange information to produce an integrated function (Damoiseaux and Greicius, 2009; Greicius et al., 2009). "
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    ABSTRACT: Recent progress in diffusion MRI and tractography algorithms as well as the launch of the Human Connectome Project (HCP) have provided brain research with an abundance of structural connectivity data. In this work, we describe and evaluate a method that can infer the structural brain network that interconnects a given set of Regions of Interest (ROIs) from tractography data. The proposed method, referred to as Minimum Asymmetry Network Inference Algorithm (MANIA), differs from prior work because it does not determine the connectivity between two ROIs based on an arbitrary connectivity threshold. Instead, we exploit a basic limitation of the tractography process: the observed streamlines from a source to a target do not provide any information about the polarity of the underlying white matter, and so if there are some fibers connecting two voxels (or two ROIs) X and Y tractography should be able in principle to follow this connection in both directions, from X to Y and from Y to X. We leverage this limitation to formulate the network inference process as an optimization problem that minimizes the (appropriately normalized) asymmetry of the observed network. We evaluate the proposed method on a noise model that randomly corrupts the observed connectivity of synthetic networks. As a case-study, we apply MANIA on diffusion MRI data from 28 healthy subjects to infer the structural network between 18 corticolimbic ROIs that are associated with various neuropsychiatric conditions including depression, anxiety and addiction.
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    • "Shared dysconnectivity in psychosis 767 is a feature of psychiatric illness in general and not psychosis in particular as we did not include nonpsychotic bipolar patients in our study. Furthermore, another study has shown no relationship between FA and values and lifetime history of psychotic symptoms in bipolar patients (McIntosh et al. 2008) and similar results have been found in a largely overlapping sample (Sussmann et al. 2009). "
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    ABSTRACT: BACKGROUND: There is an appreciable overlap in the clinical presentation, epidemiology and treatment response of the two major psychotic disorders - Schizophrenia and Bipolar Disorder. Nevertheless, the shared neurobiological correlates of these two disorders are still elusive. Using Diffusion Tensor Imaging (DTI), we sought to identify brain regions which share altered white matter connectivity across a clinical spectrum of psychotic disorders. METHODS: A sample of 41 healthy controls, 62 patients in a clinically stable state of an established psychotic disorder (40 with schizophrenia, 22 with bipolar disorder) were studied using Diffusion Tensor Imaging (DTI). Tract-Based Spatial Statistics was used in order to study group differences between patients with psychosis and healthy controls using Fractional Anisotropy (FA). Probabilistic Tractography was used in order to visualise the tracts clusters that showed significant differences between these two groups. RESULTS: The TBSS analysis revealed 5 clusters (callosal, posterior thalamic/optic, paralimbic and fronto-occipital) with reduced FA in psychosis. This reduction in FA was associated with an increase in radial diffusivity and a decrease in mode of anisotropy. Factor analysis revealed a single white matter integrity factor that predicted social and occupational functioning scores in patients irrespective of the diagnostic categorisation. CONCLUSION: Our results show that a shared white matter dysconnectivity links the two major psychotic disorders. These microstructural abnormalities predict functional outcome better than symptom-based diagnostic boundaries during a clinically stable phase of illness, highlighting the importance of seeking shared neurobiological factors that underlie the clinical spectrum of psychosis.
    Psychological Medicine 07/2014; DOI:10.1017/S0033291714001810 · 5.94 Impact Factor
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    • "In schizophrenia, diffusion MRI studies have shown significant decrease in FA in multiple WM fiber bundles relative to healthy controls using whole brain (Mori et al, 2007b; Rotarska-Jagiela et al, 2009; Schlosser et al, 2007; Shergill et al, 2007; Sussmann et al, 2009), restricted voxelbased (Douaud et al, 2007; Karlsgodt et al, 2008; Lim et al, 1999) and reconstructed tract-based (McIntosh et al, 2008; Phillips et al, 2009; Whitford et al, 2010) analysis methods. Longitudinal studies highlight the progressive nature of these deficits. "
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    ABSTRACT: Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter microstructural organisation as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal white matter. Using tract based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia.Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age and gender matched healthy controls using a 64 gradient direction sequence, (b=1300 s/mm(2)) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by DSM-IV SCID. Patients were treatment resistance, having failed to respond to at least 2 antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased RD in the genu, body and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared to controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in callosal and temporal lobe white matter regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.Neuropsychopharmacology accepted article preview online, 22 October 2013. doi:10.1038/npp.2013.294.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2013; 39(4). DOI:10.1038/npp.2013.294 · 7.05 Impact Factor
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