Diffusion Tensor Imaging Findings in First-Episode and Chronic Schizophrenia Patients

Friedman, Joseph I.; Tang, Cheuk Y.; Carpenter, David M.; Buchsbaum, Monte S.; Schmeidler, James; Flanagan, Lauren; Golembo, Shana; Kanellopoulou, Isabella; Ng, Johnny; Hof, Patrick R.; Harvey, Philip D.; Tsopelas, Nicholas D.; Stewart, Daniel G.; Davis, Kenneth L.

doi:10.1176/appi.ajp.2008.07101640

Cited by 229 publications

(196 citation statements)

References 39 publications

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“…Diffusion-weighted imaging has been relatively consistent in reporting reduced callosal FA in chronic schizophrenia (Douaud et al, 2007;Koch et al, 2010;Kubicki et al, 2008;Miyata et al, 2010;Mori et al, 2007b;RotarskaJagiela et al, 2008), including during remission (Koch et al, 2010) and less consistently in studies examining individuals at the first episode (Cheung et al, 2008;Gasparotti et al, 2009;Perez-Iglesias et al, 2010b;Peters et al, 2008;Price et al, 2005;Szeszko et al, 2005) or in earlier stages of illness (Davenport et al, 2010;Douaud et al, 2007;Kyriakopoulos and Frangou, 2009). Directly comparing first episode and chronic groups supports more severe changes in FA in the genu of the corpus callosum (Friedman et al, 2008;Kong et al, 2011), the left ILF (Friedman et al, 2008), and ALIC (Bora et al, 2011) in the chronic group including relative to the first episode group. By contrast, the large scale metaanalysis by Bora et al (2011) has reported the opposite, specifically for the genu of the corpus callosum, with FA being lower in the first episode relative to the chronic group with schizophrenia.…”

Section: Discussionmentioning

confidence: 95%

“…In WM, a single study of individuals experiencing their first psychotic episode did not detect microstructural changes (as assessed by DTI) in the corpus callosum relative to healthy controls (Price et al, 2005). Studies including both first episode and chronic patients showed that patients with chronic disease had significantly reduced FA compared with controls, reaching only a trend level in first episode patients (Friedman et al, 2008;Kong et al, 2011). This implies a progressive nature associated with illness duration in schizophrenia, as previously reported in a structural study investigating GM and WM volumes reporting a progressive reduction in the frontal WM volume in patients (Ho et al, 2003).…”

Section: Introductionmentioning

confidence: 95%

“…Recent meta-analyses of voxel-based imaging studies showed widespread clusters of GM volume reductions with no regions of volume increases, and widespread WM deficity in schizophrenia (Bora et al, 2011). Abnormalities in WM detected using diffusion MRI may indicate alterations in commissural and association fibers connecting GM regions (Ellison-Wright and Bullmore, 2009), Moreover, progressively more severe deficits in WM anisotropy have been found in crosssectional studies comparing first episode and chronic patients (Friedman et al, 2008;Kong et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…12 This hypothesis is consistent with the result of another DTI investigation of a large cohort of patients withˆrst-episode schizophrenia, which conˆrmed a reduction of FA in the inferior longitudinal fasciculus alone. 13 Patients with schizophrenia also demonstrate abnormalities of the semantic network, which are identiˆed by DTI analysis as a decrease of signiˆcant FA in the left inferior frontal white matter and are revealed by functional MR imaging as weaker connectivity between the left inferior frontal gyrus and left middle temporal gyrus. 14 Furthermore, in a 15-month study of youths (mean age: 17.02±3.37) at high risk for psychosis, TBSSbased ROI analysis revealed a signiˆcant relationship between lower baseline FA values in the medial temporal lobe and inferior longitudinal fasciculus and deterioration of social and role functioning, whereas the normal progressive increase of FA with age was not seen.…”

Section: Schizophreniamentioning

confidence: 99%

Diffusion Tensor Imaging Analysis for Psychiatric Disorders

Shizukuishi

Abe

Aoki

2013

MRMS

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The pathophysiology of psychiatric disorders is complex and cannot be easily assessed by laboratory studies. DiŠusion tensor imaging (DTI) is a magnetic resonance imaging technique increasingly used for noninvasive and quantitative evaluation of abnormalities of the cerebral white matter because it provides exquisite details on tissue microstructures and also can perform sophisticated computer-based analyses. We review basic principles of DTI; methods of diŠusion tensor analysis; recent DTIˆndings in major psychiatric diseases, such as schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorder; and factors to keep in mind when interpreting the results of DTI analysis. We recommend the frequent use of DTI as a routine clinical protocol to assess white matter abnormalities in patients with psychiatric disorders.

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“…Disruptions in WM tract structures have been consistently implicated in the pathophysiology of schizophrenia; a number of diffusion tensor imaging (DTI) studies in schizophrenia have implicated WM abnormalities in various brain regions. [6][7][8][9][10] Although there is a lack of consistency in the spatial localization of the brain regions showing reduced fractional anisotropy (FA), 11 in this regard it has been found that WM abnormalities are not localized to a specific brain region but instead reflect a diffuse process with widely dispersed focal reductions in FA that vary spatially among individuals. [12][13][14] Of all the DTI parameters examined so far, FA of water diffusion has the highest reported heritability.…”

Section: Introductionmentioning

confidence: 99%

Myelination-related genes are associated with decreased white matter integrity in schizophrenia

et al. 2015

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Disruptions in white matter (WM) tract structures have been implicated consistently in the pathophysiology of schizophrenia. Global WM integrity -as measured by fractional anisotropy (FA) -is highly heritable and may provide a good endophenotype for genetic studies of schizophrenia. WM abnormalities in schizophrenia are not localized to one specific brain region but instead reflect global low-level decreases in FA coupled with focal abnormalities. In this study, we sought to investigate whether functional gene sets associated with schizophrenia are also associated with WM integrity. We analyzed FA and genetic data from the Mind Research Network Clinical Imaging Consortium to study the effect of multiple oligodendrocyte gene sets on schizophrenia and WM integrity using a functional gene set analysis in 77 subjects with schizophrenia and 104 healthy controls. We found that a gene set involved in myelination was significantly associated with schizophrenia and FA. This gene set includes 17 genes that are expressed in oligodendrocytes and one neuronal gene (NRG1) that is known to regulate myelination. None of the genes within the gene set were associated with schizophrenia or FA individually, suggesting that no single gene was driving the association of the gene set. Our findings support the hypothesis that multiple genetic variants in myelination-related genes contribute to the observed correlation between schizophrenia and decreased WM integrity as measured by FA.

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Diffusion Tensor Imaging Findings in First-Episode and Chronic Schizophrenia Patients

Abstract: The cross-sectional data reported here suggest less widespread changes in white matter at illness onset in schizophrenia which progress in more chronic states. More definitive conclusions will require follow-up imaging of first-episode schizophrenia patients.

Cited by 229 publications

References 39 publications

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

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

Diffusion Tensor Imaging Analysis for Psychiatric Disorders

Myelination-related genes are associated with decreased white matter integrity in schizophrenia

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