Tractography Analysis of 5 White Matter Bundles and Their Clinical and Cognitive Correlates in Early-Course Schizophrenia

Seitz, Johanna; Zuo, Jessica X.; Lyall, Amanda E.; Makris, Nikos; Kikinis, Zora; Bouix, Sylvain; Pasternak, Ofer; Fredman, Eli; Duskin, Jonathan; Goldstein, Jill M.; Petryshen, Tracey L.; Mesholam-Gately, Raquelle I.; Wojcik, Joanne; McCarley, Robert W.; Seidman, Larry J.; Shenton, Martha E.; Koerte, Inga K.; Kubicki, Marek

doi:10.1093/schbul/sbv171

Cited by 46 publications

(33 citation statements)

References 81 publications

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“…Importantly, alterations of the ILF have also been associated with the presence of positive symptoms of psychosis in people with non-syndromic, early course (Ashtari et al, 2007, Seitz et al, 2016) and chronic schizophrenia (Phillips et al, 2009), as well as individuals with 22q11.2DS (Da Silva Alves et al, 2011). This is consistent with our finding of robust and tract - specific associations between alterations in FA (temporo-parietal component) and AD (temporo-occipital component) of the ILF and both positive and negative symptoms of psychosis in individuals with 22q11.2DS.…”

Section: Discussionmentioning

confidence: 99%

Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study

Tylee

Kikinis

Quinn

et al. 2017

NeuroImage: Clinical

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Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental syndrome that has been studied intensively in order to understand relationships between the genetic microdeletion, brain development, cognitive function, and the emergence of psychiatric symptoms. White matter microstructural abnormalities identified using diffusion tensor imaging methods have been reported to affect a variety of neuroanatomical tracts in 22q11.2DS. In the present study, we sought to combine two discovery-based approaches: (1) white matter query language was used to parcellate the brain's white matter into tracts connecting pairs of 34, bilateral cortical regions and (2) the diffusion imaging characteristics of the resulting tracts were analyzed using a machine-learning method called support vector machine in order to optimize the selection of a set of imaging features that maximally discriminated 22q11.2DS and comparison subjects. With this unique approach, we both confirmed previously-recognized 22q11.2DS-related abnormalities in the inferior longitudinal fasciculus (ILF), and identified, for the first time, 22q11.2DS-related anomalies in the middle longitudinal fascicle and the extreme capsule, which may have been overlooked in previous, hypothesis-guided studies. We further observed that, in participants with 22q11.2DS, ILF metrics were significantly associated with positive prodromal symptoms of psychosis.

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Section: Discussionmentioning

confidence: 99%

Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study

Tylee

Kikinis

Quinn

et al. 2017

NeuroImage: Clinical

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“…White matter abnormalities are diffuse in subjects with schizophrenia, with globally decreased levels of fractional anisotropy (FA) and increased radial diffusivity (RD) (Chavarria‐Siles et al, ; Reid et al, ), proxy measures for myelin integrity. Deficits are evident diffusely in frontomedial white matter tracts (Drakesmith et al, ), orbitofrontal cortex, posterior parietal cortex (Green et al, ), arcuate fasciculus, cingulum bundle, and inferior longitudinal fasciculus (Oestreich et al, ; Seitz et al, ). The apparently more global disruptions to white matter in schizophrenia compared to other neuropsychiatric disorders are consistent with the more severe and complex nature of dysfunction in schizophrenia.…”

Section: Psychiatric Disordersmentioning

confidence: 99%

Bad wrap: Myelin and myelin plasticity in health and disease

Gibson

Geraghty

Monje

2017

Developmental Neurobiology

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Human central nervous system myelin development extends well into the fourth decade of life, and this protracted period underscores the potential for experience to modulate myelination. The concept of myelin plasticity implies adaptability in myelin structure and function in response to experiences during development and beyond. Mounting evidence supports this concept of neuronal activity-regulated changes in myelin-forming cells, including oligodendrocyte precursor cell proliferation, oligodendrogenesis and modulation of myelin microstructure. In healthy individuals, myelin plasticity in associative white matter structures of the brain is implicated in learning and motor function in both rodents and humans. Activity-dependent changes in myelin-forming cells may influence the function of neural networks that depend on the convergence of numerous neural signals on both a temporal and spatial scale. However, dysregulation of myelin plasticity can disadvantageously alter myelin microstructure and result in aberrant circuit function or contribute to pathological cell proliferation. Emerging roles for myelin plasticity in normal neurological function and in disease are discussed. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 123-135, 2018.

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“…Post‐mortem results show down‐regulated expression of white matter‐related genes and proteins as well as oligodendrocyte pathology (Beasley et al, ; Flynn et al, ; Hakak et al, ; Hercher, Chopra, & Beasley, ). Imaging studies also show decreased white matter volume as well as reductions in fractional anisotropy and diffusion tensor imaging, both imaging markers of white matter integrity (Agartz, Andersson, & Skare, ; Foong et al, ; Kubicki et al, ; McCarthy‐Jones et al, ; Samartzis, Dima, Fusar‐Poli, & Kyriakopoulos, ; Seitz et al, ; Whitford et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…The aforementioned white matter tracts connect regions of the brain that are abnormal in schizophrenia (Fornito et al, ; Friston, ). Specifically, imaging studies have demonstrated deficits in connectivity in schizophrenia patients in three white matter tracts of interest: the CC, the CB, and the arcuate fasciculus (AF; Agartz, Andersson, & Skare, ; Douaud et al, , ; Foong et al, ; Gasparotti et al, ; Kubicki et al, ; Kyriakopoulos, Bargiotas, Barker, & Frangou, ; McCarthy‐Jones et al, ; Price et al, ; Seitz et al, ; Whitford et al, ). Furthermore, deficits in the CC have been observed in first‐episode patients (Cheung et al, ; Dekker et al, ; Federspiel et al, ; Kyriakopoulos & Frangou, ; Perez‐Iglesias et al, ) and clinical high‐risk subjects (Hoptman et al, ).…”

Section: Introductionmentioning

confidence: 99%

Pathology of white matter integrity in three major white matter fasciculi: A post‐mortem study of schizophrenia and treatment status

Schoonover

Farmer

Cash

et al. 2019

British J Pharmacology

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Background and Purpose:Imaging studies have shown that people with schizophrenia exhibit abnormal connectivity termed "dysconnectivity" in several white matter tracts, including the cingulum bundle (CB), corpus callosum (CC), and arcuate fasciculus (AF). This study aimed to elucidate potential contributors to schizophrenia "dysconnectivity."Experimental Approach: Western blot analysis was used to compare protein levels of myelin basic protein, neurofilament heavy, autophagosome marker LC3, and microtubule marker α-tubulin in post-mortem human CB, CC, and AF in schizophrenia subjects (SZ) and matched normal controls (NC). Additionally, SZ cases were subdivided by treatment status: off-medication (OFF) or on-medication (ON). Key Results:In the CC, the combined SZ group exhibited less neurofilament heavy protein than the NCs. In the CB, the combined SZ group had similar levels of αtubulin protein versus NC, but OFF subjects had increased α-tubulin protein versus ON and NCs. There were significant correlations between α-tubulin and all other proteins but only in the CB. The strong negative relationship between α-tubulin versus myelin basic protein and α-tubulin versus LC3 in NCs was absent in SZs; coefficients comparison showed significant differences. Preliminary race analyses revealed that African American SZ had less AF α-tubulin than Caucasian SZ and African American normal controls. Conclusions and Implications:The results show a relationship between tract-and protein-specific abnormalities and diagnosis, treatment, and race. These data suggest there is a dysregulation of the relationship between α-tubulin and the other markers of white matter integrity observed in the CB in schizophrenia.

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Tractography Analysis of 5 White Matter Bundles and Their Clinical and Cognitive Correlates in Early-Course Schizophrenia

Abstract: We observed white matter alterations in the right CB, ILF, and AF, possibly caused by myelin disruptions. The structural abnormalities interact with cognitive performance, and are linked to clinical symptoms.

Cited by 46 publications

References 81 publications

Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study

Machine-learning classification of 22q11.2 deletion syndrome: A diffusion tensor imaging study

Bad wrap: Myelin and myelin plasticity in health and disease

Pathology of white matter integrity in three major white matter fasciculi: A post‐mortem study of schizophrenia and treatment status

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