A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

Cheung, Vincent C. K.; Cheung, CW; McAlonan, Gráinne; Deng, Yi; Wong, Janet; Yip, Lawrance; Tai, KS; Khong, Pek‐Lan; Sham, Pak C.; Chua, Siew E.

doi:10.1017/s0033291707001808

Cited by 186 publications

(167 citation statements)

References 61 publications

(138 reference statements)

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“…This may reflect reduced axonal number or packing density, cellular membrane abnormalities that increase permeability including possible loss of myelin, or inconsistent fiber orientation. These findings may be confounded by exposure to nonclozapine psychotropic medications; however, concurrent findings in studies involving subjects who are naive to psychotropic medication (Cheung et al, 2008;Gasparotti et al, 2009;Karlsgodt et al, 2009;Perez-Iglesias et al, 2010a;Zou et al, 2008) supporting the hypothesis that a portion of these deficits are due to the pathophysiology of schizophrenia. Postmortem studies provide support for a contribution of reduced axonal packing density, abnormal glial cell arrangement or function, and reduced myelin in schizophrenia.…”

Section: Discussionmentioning

confidence: 85%

“…Postmortem studies have shown a genderdiagnosis effect of reduced axonal number (Highley et al, 1999a), oligodendrocyte density loss (Hof et al, 2003), and lower levels of immunoreactivity of oligodendrocyte-associated proteins in the genu of the corpus callosum (Flynn et al, 2003). 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.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, it remains possible that typical and atypical antipsychotic medications contribute to deficits present at the time of scanning. Studies on drug-naive first episode patients also demonstrate reduced FA in patients with schizophrenia indicating that at least some of these WM abnormalities are likely to be related to the pathophysiology of schizophrenia (Cheung et al, 2008).…”

Section: Discussionmentioning

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: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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“…4 The relevance of DTI abnormalities in the early phase of schizophrenia is further supported by the positive association between positive symptoms and fractional anisotropy (FA) values of the superior and inferior longitudinal fasciculi and inferior fronto-occipital fasciculus in never-medicated patients with schizophrenia. 5,10 In addition, most studies [4][5][6][7][8] have investigated FA only, and none of them have assessed GM volumes in the same sample.…”

mentioning

confidence: 99%

“…To date, however, only a few studies [4][5][6][7][8][9] have adopted this strategy showing WM changes compared with healthy participants in a variable pattern of brain regions including the splenium of the corpus callosum, 4,6 superior longitudinal fasciculus, 7,8 anterior 9 and posterior 4 limbs of the internal capsule, and fronto-occipital fasciculus. 4 The relevance of DTI abnormalities in the early phase of schizophrenia is further supported by the positive association between positive symptoms and fractional anisotropy (FA) values of the superior and inferior longitudinal fasciculi and inferior fronto-occipital fasciculus in never-medicated patients with schizophrenia. 5,10 In addition, most studies [4][5][6][7][8] have investigated FA only, and none of them have assessed GM volumes in the same sample.…”

mentioning

confidence: 99%

Patterns of Brain Structural Changes in First-Contact, Antipsychotic Drug-Naïve Patients with Schizophrenia

Filippi

Canu

Gasparotti

et al. 2013

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Previous studies have suggested that structural changes do occur in the brain of patients with schizophrenia compared with healthy control participants. However, findings from such studies are inconclusive, probably because of the different methodologic approaches, the clinical heterogeneity of patient samples, and also the fact that patients enrolled were treated with antipsychotic drugs. The aim of this study was to investigate brain GM volumes and intrinsic structural WM changes in first-contact, antipsychotic drug-naïve patients with schizophrenia.

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Genome‐wide supported psychosis risk variant in ZNF804A gene and impact on cortico–limbic WM integrity in schizophrenia

Kuswanto

Woon

Zheng

et al. 2012

American J of Med Genetics Pt B

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Genome-wide association, case association genetic and meta-analytic studies have highlighted ZNF804A as a robust genome-wide supported susceptibility gene for schizophrenia (SCZ). In view of the possible involvement of ZNF804A gene in early neurodevelopment and cellular processes including oligodendrocyte proliferation and differentiation, we examined the effect of ZNF804A on brain WM (WM) integrity in patients with SCZ. Based on extant data in healthy controls (HC), we hypothesized that ZNF804A risk variant rs1344706 is associated with lower fractional anisotropy (FA) in brain regions within cortico-limbic circuits, namely frontal, parietal, medial temporal lobes, and cingulate gyri in SCZ. A total of 200 Chinese participants (125 patients with DSM-IV diagnosis of SCZ and 75 controls) were genotyped using blood samples, a subset of 153 participants (89 patients with DSM-IV diagnosis of SCZ and 64 controls) underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). There are significant effects of diagnosis (left cingulate gyrus: Adjusted F(1,149) = 9.36, P = 0.003) and diagnosis-genotype interactions (left parietal lobe: Adjusted F(1,147) = 7.39, P = 0.007; right parietal lobe: Adjusted F(1,147) = 6.95, P = 0.009; right medial temporal lobe: Adjusted F(1,147) = 8.79, P = 0.004; left cingulate gyrus: Adjusted F(1,147) = 8.02, P = 0.005). Specifically, we found that patients with SCZ who are risk T homozygotes have lower FA in bilateral parietal lobes, and left cingulate gyrus compared with G carriers. Compared with risk T homozygotes in HC, patients with SCZ who are risk T homozygotes have decreased FA in bilateral parietal lobes, and left cingulate gyrus as well as right medial temporal lobe. Our findings suggest that ZNF804A risk variant influence WM integrity involving cortico-limbic brain regions in SCZ and highlight the importance of investigating the impact of genome-wide supported risk factors on intermediate phenotypes with potential to shed light on the neurobiology of SCZ.

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A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

Abstract: Widespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

Cited by 186 publications

References 61 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

Patterns of Brain Structural Changes in First-Contact, Antipsychotic Drug-Naïve Patients with Schizophrenia

Genome‐wide supported psychosis risk variant in ZNF804A gene and impact on cortico–limbic WM integrity in schizophrenia

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