Article

Abnormal white matter microstructure in schizophrenia: A voxelwise analysis of axial and radial diffusivity

Melbourne Neuropsychiatry Centre, The University of Melbourne, Victoria, Australia.
Schizophrenia Research (Impact Factor: 3.92). 05/2008; 101(1-3):106-10. DOI: 10.1016/j.schres.2007.12.489
Source: PubMed

ABSTRACT

Diffusion Tensor Imaging (DTI) investigations in schizophrenia have provided evidence of impairment in white matter as indicated by reduced fractional anisotropy (FA). However, the neuropathological implications of these findings remain unclear. In the current study, we conducted a voxelwise analysis of the constituent parameters of FA, Axial (lambda(||)) and Radial Diffusivity (lambda( upper left and right quadrants)), in 14 male participants with schizophrenia and 14 age, gender, education, and premorbid intelligence matched healthy controls. Significantly reduced FA and higher Radial Diffusivity were concurrently observed in several major white matter tracts in the schizophrenia group. This finding suggests that the loss of white matter integrity in schizophrenia is the result of demyelination and/or changes to the axonal cytoskeleton rather than gross axonal damage.

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    • "Although a few genetic studies suggested myelination in the OCD pathophysiology (Zai et al., 2004;Stewart et al., 2007), we can only speculate about possible disruption of myelin integrity contributing to the white matter abnormalities in the left cingulum bundle. A similar pattern of lower FA in combination with higher RD (and normal AD values) has also been reported for autism, schizophrenia, and depression (Alexander et al., 2007;Ashtari et al., 2007;Lee et al., 2007;Michael et al., 2008;Seal et al., 2008;Whitford et al., 2010;Korgaonkar et al., 2011). With regard to both FA and RD, the unaffected siblings seem to represent an intermediate group between patients and HC, suggesting that white matter alterations can be considered, at least partly, an endophenotype of OCD. "
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    ABSTRACT: Objective: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with moderate genetic influences and white matter abnormalities in frontal-striatal and limbic regions. Inconsistencies in reported white matter results from diffusion tensor imaging (DTI) studies can be explained, at least partly, by medication use and between-group differences in disease profile and stage. We used a family design aiming to establish whether white matter abnormalities, if present in un-medicated OCD patients, also exist in their unaffected siblings. Method: Forty-four OCD patients, un-medicated for at least the past 4 weeks, 15 of their unaffected siblings, and 37 healthy controls (HC) underwent DTI using a 3-Tesla MRI-scanner. Data analysis was done using tract-based spatial statistics (TBSS). Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values were compared within seven skeletonised regions of interest (ROIs), i.e., corpus callosum, bilateral cingulum bundle, bilateral inferior longitudinal fasciculus/frontal-occipital fasciculus (ILF/FOF) and bilateral superior longitudinal fasciculus (SLF). Results: Un-medicated OCD patients, compared with HC, had significantly lower FA in the left cingulum bundle. FA was trend-significantly lower in all other ROIs, except for the corpus callosum. Significant three-group differences in FA (and in RD at trend-significant level) were observed in the left cingulum bundle, with the unaffected siblings representing an intermediate group between OCD patients and HC. Conclusions: OCD patients showed lower FA in the left cingulum bundle, partly driven by trend-significantly higher values in RD. Since the unaffected siblings were found to be an intermediate group between OCD patients and HC, this white matter alteration may be considered an endophenotype for OCD.
    Full-text · Article · Jan 2016 · Frontiers in Neuroscience
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    • "Abnormal myelination has been documented in postmortem studies through altered oligodendrocytes, abnormalities in myelination of fibers, and changes in the expression profiles of myelin-related genes in the brains of patients diagnosed with schizophrenia (Hakak et al., 2001; Haroutunian and Davis, 2007; Haroutunian et al., 2007; Tkachev et al., 2003; Uranova et al., 2001). Studies using dMRI reported reduced FA and increased RD for several fiber tracts, including fornix, cingulum, inferior longitudinal fasciculus , anterior limb of the internal capsule, frontostriatal connections and corpus callosum, and reconfirmed abnormal myelination of axons in vivo (Abdul-Rahman et al., 2011; Ashtari et al., 2007; Carletti et al., 2012; Holleran et al., 2014; Levitt et al., 2012; Quan et al., 2013; Seal et al., 2008; Whitford et al., 2010). Our study, which reports decreases in FA and increases in trace and RD in the AC, extends the list of tracts impacted by abnormal myelination of the axons. "
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    ABSTRACT: The Anterior Commissure (AC) is an important interhemispheric pathway that connects contralateral temporal lobes and orbitofrontal areas. The role of the AC is not yet well understood, although abnormalities in this white matter tract have been reported in patients diagnosed with chronic schizophrenia. However, it is not known whether changes in the AC are present at earlier stages of the disease. Diffusion Magnetic Resonance Images (dMRI) were acquired from 17 First Episode Schizophrenia Patients (FESZ) and 20 healthy controls. The AC was reconstructed using a streamline tractography approach. DMRI measures, including Fractional Anisotropy (FA), Trace, Axial Diffusivity (AD) and Radial Diffusivity (RD) were computed in order to assess microstructural changes in the AC. FA was reduced, while trace and RD showed increases in FESZ. AD did not show differences between groups. The observed changes in these dMRI measures, namely reductions in FA and increases in trace and RD, without changes in AD, likely point to myelin abnormalities of this white matter tract, and provide evidence of white matter pathology extant in the early phases of schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Schizophrenia Research
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    • "Abnormal myelination has been documented in postmortem studies through altered oligodendrocytes, abnormalities in myelination of fibers, and changes in the expression profiles of myelin-related genes in the brains of patients diagnosed with schizophrenia (Hakak et al., 2001; Haroutunian and Davis, 2007; Haroutunian et al., 2007; Tkachev et al., 2003; Uranova et al., 2001). Studies using dMRI reported reduced FA and increased RD for several fiber tracts, including fornix, cingulum, inferior longitudinal fasciculus , anterior limb of the internal capsule, frontostriatal connections and corpus callosum, and reconfirmed abnormal myelination of axons in vivo (Abdul-Rahman et al., 2011; Ashtari et al., 2007; Carletti et al., 2012; Holleran et al., 2014; Levitt et al., 2012; Quan et al., 2013; Seal et al., 2008; Whitford et al., 2010). Our study, which reports decreases in FA and increases in trace and RD in the AC, extends the list of tracts impacted by abnormal myelination of the axons. "
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    ABSTRACT: Abstract BACKGROUND: The Anterior Commissure (AC) is an important interhemispheric pathway that connects contralateral temporal lobes and orbitofrontal areas. The role of the AC is not yet well understood, although abnormalities in this white matter tract have been reported in patients diagnosed with chronic schizophrenia. However, it is not known whether changes in the AC are present at earlier stages of the disease. METHODS: Diffusion Magnetic Resonance Images (dMRI) were acquired from 17 First Episode Schizophrenia Patients (FESZ) and 20 healthy controls. The AC was reconstructed using a streamline tractography approach. DMRI measures, including Fractional Anisotropy (FA), Trace, Axial Diffusivity (AD) and Radial Diffusivity (RD) were computed in order to assess microstructural changes in the AC. RESULTS: FA was reduced, while trace and RD showed increases in FESZ. AD did not show differences between groups. CONCLUSION: The observed changes in these dMRI measures, namely reductions in FA and increases in trace and RD, without changes in AD, likely point to myelin abnormalities of this white matter tract, and provide evidence of white matter pathology extant in the early phases of schizophrenia.
    Full-text · Article · Jan 2015 · Schizophrenia Research
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