White Matter Alterations in Deficit Schizophrenia

Rowland, Laura M.; Spieker, Elena A.; Francis, Alan; Barker, Peter B.; Carpenter, William T.; Boyer, Robert

doi:10.1038/npp.2008.207

Cited by 130 publications

(118 citation statements)

References 52 publications

(55 reference statements)

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“…A parsimonious explanation of the varied and multiple presentations of SCZ should involve the whole brain. White matter abnormalities have been implicated in varied psychopathological processes such as positive symptoms (Hubl et al, 2004;Skelly et al, 2008), tardive dyskinesia (Bai et al, 2009), negative symptoms (Szeszko et al, 2008), deficit syndrome (Rowland et al, 2009), lack of insight (Antonius et al, 2011), and cognition (Szeszko et al, 2008). Our results, in agreement with results from other investigations (e.g., Kanaan et al, 2009;Skelly et al, 2008), suggest that white matter change is diffuse, consistent with multiple psychopathological abnormalities.…”

Section: Discussionsupporting

confidence: 83%

Diffuse Abnormality of Low to Moderately Organized White Matter in Schizophrenia

et al. 2011

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Increasing evidence suggests that abnormal white matter is central to the pathophysiology and, potentially, the pathogenesis of schizophrenia (SCZ). The spatial distribution of observed abnormalities and the type of white matter involved remain to be elucidated. Seventeen chronically ill individuals with SCZ and 17 age-and gender-matched controls were studied using a 3T magnetic resonance imaging diffusion tensor imaging protocol designed to examine the abnormalities of white matter by region and by level of architectural infrastructure as assessed by fractional anisotropy (FA) in native space. After assessing whole-brain FA, FA was divided into quartiles, capturing all brain regions with FA values from 0 to 0.25, 0.25 to 0.5, 0.5 to 0.75, and 0.75 to 1.0. Mean wholebrain FA was 4.6% smaller in the SCZ group than in healthy controls. This difference was largely accounted for by FA values from the second quartile (between 0.25 and 0.5). Second quartile FA was decreased in all 130 brain regions of the template in the SCZ group, with the difference reaching statistical significance in 41 regions. Correspondingly, the amount of brain tissue with an FA of *0.4 was significantly reduced in the SCZ group, while the amount of brain tissue falling in the lowest quartile of FA was increased. These findings strongly imply a diffuse loss of white matter integrity in SCZ. Our finding that the loss of integrity disproportionately involves white matter of low to moderate organization suggests an approach to the specificity of white matter abnormalities in SCZ based on microstructure rather than spatial distribution.

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Section: Discussionsupporting

confidence: 83%

Diffuse Abnormality of Low to Moderately Organized White Matter in Schizophrenia

et al. 2011

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“…Electrophysiological research in patients provides evidence for a contribution of abnormal neural oscillations to cognitive deficits (Uhlhaas and Singer, 2010). Reduced structural connectivity including the superior longitudinal fasciculus (Shergill et al, 2007;Rowland et al, 2009), which connects frontal and parietal cortices and is critically involved in WM (Karlsgodt et al, 2010), also supports the notion of dysconnectivity. However, despite the well replicated impairment of WM and a strong focus on dlPFC dysfunction in schizophrenia, direct evidence for WM-dependent alterations in effective connectivity underlying dlPFC inefficiency is still lacking.…”

Section: Introductionmentioning

confidence: 76%

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

et al. 2012

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The neural mechanisms behind cognitive deficits in schizophrenia still remain unclear. Functional neuroimaging studies on working memory (WM) yielded inconsistent results, suggesting task performance as a moderating variable of prefrontal activation. Beyond regional specific activation, disordered integration of brain regions was supposed as a critical pathophysiological mechanism of cognitive deficits in schizophrenia. Here, we first hypothesized that prefrontal activation implicated in WM depends primarily on task performance and therefore stratified participants into performance subgroups. Second, in line with the dysconnectivity hypothesis, we asked whether connectivity in the prefrontal-parietal network underlying WM is altered in all patients. We used functional magnetic resonance imaging in human subjects (41 schizophrenia patients, 42 healthy controls) and dynamic causal modeling to examine effective connectivity during a WM task. In line with our first hypothesis, we found that prefrontal activation was differentially modulated by task performance: there was a significant task by group by performance interaction revealing an increase of activation with performance in patients and a decrease with performance in controls. Beyond that, we show for the first time that WM-dependent effective connectivity from prefrontal to parietal cortex is reduced in all schizophrenia patients. This finding was independent of performance. In conclusion, our results are in line with the highly influential hypothesis that the relationship between WM performance and prefrontal activation follows an inverted U-shaped function. Moreover, this study in a large sample of patients reveals a mechanism underlying prefrontal inefficiency and cognitive deficits in schizophrenia, thereby providing direct experimental evidence for the dysconnectivity hypothesis.

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“…Several additional regions beyond the callosal body have been implicated in chronic schizophrenia including SLF (Rotarska-Jagiela et al, 2009;Rowland et al, 2009;Seok et al, 2007;Shergill et al, 2007;Szeszko et al, 2008) DMRI study in severe chronic schizophrenia L Holleran et al Jagiela et al, 2009;Seal et al, 2008), UF (Burns et al, 2003;McIntosh et al, 2008;Miyata et al, 2010;Mori et al, 2007b;Seal et al, 2008), internal capsule (Buchsbaum et al, 1998;Lim et al, 1999), external capsule (Rotarska-Jagiela et al, 2009;Seal et al, 2008), cingulum (Kubicki et al, 2003;Mori et al, 2007b;Seok et al, 2007;Sun et al, 2003;Wang et al, 2004), fornix (Fitzsimmons et al, 2009;Kuroki et al, 2006), anterior commissure (Choi et al, 2011), arcuate fasciculus (Burns et al, 2003;Phillips et al, 2009), and cerebellar peduncles (Okugawa et al, 2006;Seok et al, 2007). Differences in RD are less examined, yet to date increases have been detected in the external capsule (Seal et al, 2008), in the left inferior temporal and left occipital lobe (Ashtari et al, 2007), in temporal WM (Koch et al, 2011), and in the middle cerebellar peduncle (Okugawa et al, 2006), and increased mean diffusivity has been detected in the splenium of the corpus callosum (Foong et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Holleran

Ahmed

Anderson‐Schmidt

et al. 2013

Neuropsychopharmacol

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Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. 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 ¼ 1300 s/mm 2 ) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two 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 radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM 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.

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White Matter Alterations in Deficit Schizophrenia

Cited by 130 publications

References 52 publications

Diffuse Abnormality of Low to Moderately Organized White Matter in Schizophrenia

Diffuse Abnormality of Low to Moderately Organized White Matter in Schizophrenia

Reduced Prefrontal-Parietal Effective Connectivity and Working Memory Deficits in Schizophrenia

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

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