White matter alterations in the corpus callosum of adolescents with first-admission schizophrenia

Henze, Romy; Brunner, Romuald; Thiemann, Ulf; Parzer, Peter; Klein, Jan; Resch, Franz; Stieltjes, Bram

doi:10.1016/j.neulet.2012.02.032

Cited by 45 publications

(24 citation statements)

References 26 publications

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“…The corpus callosum was chosen for scientific and feasibility purposes. Scientifically, it was chosen because it consistently shows significant schizophrenia-related WM deficits (33,44,45). The corpus callosum was also chosen because it is composed of commissural fibers that facilitate long-interhemispheric signal transmission and shows strong phenotypic and genetic associations with processing speed in humans and primates (46)(47)(48)(49).…”

Section: Methodsmentioning

confidence: 99%

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Kochunov

Rowland

Fieremans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Schizophrenia, a devastating psychiatric illness with onset in the late teens to early 20s, is thought to involve disrupted brain connectivity. Functional and structural disconnections of cortical networks may underlie various cognitive deficits, including a substantial reduction in the speed of information processing in schizophrenia patients compared with controls. Myelinated white matter supports the speed of electrical signal transmission in the brain. To examine possible neuroanatomical sources of cognitive deficits, we used a comprehensive diffusion-weighted imaging (DWI) protocol and characterized the white matter diffusion signals using diffusion kurtosis imaging (DKI) and permeability-diffusivity imaging (PDI) in patients (n = 74), their nonill siblings (n = 41), and healthy controls (n = 113). Diffusion parameters that showed significant patient-control differences also explained the patient-control differences in processing speed. This association was also found for the nonill siblings of the patients. The association was specific to processing-speed abnormality but not specific to working memory abnormality or psychiatric symptoms. Our findings show that advanced diffusion MRI in white matter may capture microstructural connectivity patterns and mechanisms that govern the association between a core neurocognitive measureprocessing speed-and neurobiological deficits in schizophrenia that are detectable with in vivo brain scans. These non-Gaussian diffusion white matter metrics are promising surrogate imaging markers for modeling cognitive deficits and perhaps, guiding treatment development in schizophrenia.diffusion-weighted imaging | schizophrenia | processing speed | cognitive deficits | endophenotypes A lthough pharmaceutical interventions alleviate clinical symptoms, such as delusions and hallucinations, for some patients, schizophrenia remains a debilitating illness, often times leading to long-term disabilities and severe cognitive deficits (1). Discovering the underlying neurobiology behind these core cognitive deficits in schizophrenia patients may present a viable strategy to identify biomarkers for supporting pathophysiology and comprehensive treatment research. Two decades of research have implicated impaired brain connectivity as a source of functional disability in schizophrenia (1, 2). Delayed information processing is one of the most robust cognitive deficits (3, 4) and may contribute to other cognitive impairments in working memory and executive function (4-6).Myelinated axons in the brain's white matter (WM) support its functionality by propagating electric signal transmissions through saltatory conductance (7,8). Reports of WM abnormalities in patients with schizophrenia are common and include reduced fractional anisotropy (FA) of water diffusion measured by diffusion tensor imaging (DTI) MRI (9-11) as well as reduced axonal myelin levels and glial cell density in postmortem brain studies (12)(13)(14). Identifying the key WM microstructural properties that explain the patient-control...

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Section: Methodsmentioning

confidence: 99%

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Kochunov

Rowland

Fieremans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…These studies have revealed disrupted white matter integrity (i.e., FA reductions) in multiple white matter tracts across the phases of illness, including individuals at clinical high-risk (CHR) for psychosis (Karlsgodt et al, 2009; Bloemen et al, 2010; Carletti et al, 2012), first-episode (Peters et al, 2008; Price et al, 2008; Luck et al, 2010; Lee et al, 2013), chronically ill (Friedman et al, 2008; Kong et al, 2011), and medication-naïve schizophrenia patients (Guo et al, 2012; Henze et al, 2012; Liu et al, 2013). The most consistently reported abnormalities are in fronto-temporal and fronto-limbic tracts (Ellison-Wright and Bullmore, 2009; Kuswanto et al, 2012; Samartzis et al, 2014), including the superior longitudinal fasciculus (SLF; Szeszko et al, 2008; Clemm von Hohenberg et al, 2014), one of the largest long-range fiber tracts in the brain which connects the parietal to frontal lobes, and the uncinate fasciculus (Burns et al, 2003; Szeszko et al, 2005; Kawashima et al, 2009; Kitis et al, 2012), a tract which connects regions of the limbic system with orbitofrontal cortex.…”

Section: Introductionmentioning

confidence: 99%

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

Jalbrzikowski

Villalon‐Reina

Karlsgodt

et al. 2014

Front. Behav. Neurosci.

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22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk.

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“…The main direction of each point was in accordance with the vector direction of maximum eigenvalue. FA was calculated according to the formula below (Henze et al 2012): …”

Section: Mri Image Acquisitionmentioning

confidence: 99%

“…Using standard magnetic resonance imaging (MRI) analysis, volume reductions in total and regional white matter areas of schizophrenic patients have been observed; however, MRI has generally reported only subtle volume reductions (Makris et al 2010). Neuropathological and genetic studies of postmortem tissues have observed the pathology of oligodendrocytes in the white matter of patients with schizophrenia (Henze et al 2012). Therefore, live imaging of white matter microstructure and connectivity could provide more information for the management of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Application of diffusion tensor imaging for detecting structural changes in the brain of schizophrenic patients

Situ

Liao

Zhou

et al. 2014

International Journal of Psychiatry in Clinical Practice

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White matter alterations in the corpus callosum of adolescents with first-admission schizophrenia

Cited by 45 publications

References 26 publications

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia

Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome

Application of diffusion tensor imaging for detecting structural changes in the brain of schizophrenic patients

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