Diffusion Tensor Imaging in Schizophrenia

Buchsbaum, Monte S.; Friedman, Joseph I.; Buchsbaum, Bradley R.; Chu, King-Wai; Hazlett, Erin A.; Newmark, Randall E.; Schneiderman, Jason S.; Torosjan, Yuliya; Tang, Cheuk Y.; Hof, Patrick R.; Stewart, Daniel G.; Davis, Kenneth L.; Gorman, Jack

doi:10.1016/j.biopsych.2005.11.028

Cited by 114 publications

(80 citation statements)

References 44 publications

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“…[76][77][78][79] These oligodendrocyte abnormalities may in turn contribute to the loss of coherence of axon tracts, and reduced connectivity, in schizophrenia. 80,81 Alterations in NRG1-ERBB4 and/or PTPRZ1 signaling may cause these oligodendrocyte abnormalities, in addition to potential neuronal effects.…”

Section: Discussionmentioning

confidence: 99%

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

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Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI scaffolding proteins as ERBB4-binding proteins. After validating the interaction of MAGI proteins with ERBB4 in mammalian cells, we demonstrated that ERBB4 expression, alone or in combination with ERBB2 or ERBB3, led to the tyrosine phosphorylation of MAGI proteins, and that this could be further enhanced with receptor activation by neuregulin. As MAGI proteins were previously shown to interact with receptor phosphotyrosine phosphatase b/f (RPTPb), we postulated that simultaneous binding of MAGI proteins to RPTPb and ERBB4 forms a phosphotyrosine kinase/phosphotyrosine phosphatase complex. Studies in cultured cells confirmed both a spatial and functional association between ERBB4, MAGI and RPTPb. Given the evidence for this functional association, we examined the genes coding for MAGI and RPTPb for genetic association with schizophrenia in a Caucasian United Kingdom case-control cohort (n = B1400). PTPRZ1, which codes for RPTPb, showed significant, gene-wide and hypothesis-wide association with schizophrenia in our study (best individual single-nucleotide polymorphism allelic P = 0.0003; gene-wide P = 0.0064; hypothesiswide P = 0.026). The data provide evidence for a role of PTPRZ1, and for RPTPb signaling abnormalities, in the etiology of schizophrenia. Furthermore, the data indicate a role for RPTPb in the modulation of ERBB4 signaling that may in turn provide further support for an important role of neuregulin/ERBB4 signaling in the molecular basis of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

et al. 2007

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“…Early studies showed widespread anisotropic alterations in the integrity of prefrontal white matter (Buchsbaum et al, 1998) and whole-brain white matter (Lim et al, 1999). Subsequent studies reported lower anisotropic diffusion within specific regions including the corpus callosum (Ardekani et al, 2003;Kubicki et al, 2005), internal capsule (Kubicki et al, 2005; Szeszko et al, 2005a; Buchsbaum et al, 2006;Mitelman et al, 2007), anterior cingulate (Kumra et al, 2005;Wang et al, 2004;Kubicki et al, 2003), arcuate fasciculus (Kubicki et al, 2005;Burns et al, 2003), and inferior longitudinal fasciculus (Hubl et al, 2004). Additional studies reported a lack of normal asymmetry in white matter regions such as the internal capsule (Park et al, 2004), uncinate fasciculus (Park et al, 2004;Kubicki et al, 2002), and superior longitudinal fasciculus (Park et al, 2004) in patients compared to healthy volunteers and that internal capsule abnormalities are associated with worse outcome among patients (Brickman et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

Szeszko

Robinson

Ashtari

et al. 2007

Neuropsychopharmacol

225

184

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The objective of this study was to investigate the clinical and neuropsychological correlates of white matter abnormalities in patients with schizophrenia studied early in the course of illness. A total of 33 (21 male/12 female) patients with recent onset schizophrenia and 30 (18 male/12 female) healthy volunteers completed structural and diffusion tensor imaging exams. Patients also received clinical and neuropsychological assessments. Fractional anisotropy (FA) maps were compared between groups in the white matter using a voxelwise analysis following intersubject registration to Talairach space and correlated with functional indices. Compared to healthy volunteers, patients demonstrated significantly (po0.001, cluster size X100) lower FA within temporal lobe white matter regions corresponding approximately to the right and left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. There were no areas of significantly higher FA in patients compared to healthy volunteers. Lower FA in the bilateral uncinate fasciculus correlated significantly with greater severity of negative symptoms (alogia and affective flattening), and worse verbal learning/memory functioning. In addition, higher FA in the inferior fronto-occipital fasciculus correlated significantly with greater severity of delusions and hallucinations. White matter abnormalities are evident in patients with schizophrenia early in the course of illness, appearing most robust in left temporal regions. These abnormalities have clinical and neuropsychological correlates, which may be useful in further characterizing structure-function relations in schizophrenia and constraining neurobiological models of the disorder.

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“…These observations "underscore the importance of evaluating white matter fiber tract abnormalities in schizophrenia" (Kubicki et al, 2005) which may contribute to the hypothesized disordered connectivity between brain regions in schizophrenia (Friston, 1998). A number of recent studies have applied diffusion tensor imaging (DTI), a magnetic resonance imaging method sensitive to white matter integrity, to the study of schizophrenia; using the apparent diffusion coefficient (ADC) or fractional anisotropy (FA) measures, the majority of these find white matter deficits associated with the disease (Kubicki et al, 2007;Mori et al, 2007;Shergill et al, 2007;Buchsbaum et al, 2006;Rose et al, 2006;Jones et al, 2005b;Kitamura et al, 2005;Kubicki et al, 2005;Kanaan et al, 2005;Kumra et al, 2005;Szeszko et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Diffusion tensor imaging in schizophrenia: Relationship to symptoms

Skelly

Calhoun

Meda

et al. 2008

Schizophrenia Research

117

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In this diffusion tensor imaging (DTI) study, the authors investigated white matter integrity in schizophrenia and the relationships between white matter alterations and specific symptoms of the disorder. We compared DTI images of 25 schizophrenia patients and 25 matched healthy controls and performed voxel-wise correlational analyses using the patient's DTI data and their severity scores of positive and negative symptoms. We found diffuse deficits in multiple types of white matter tracts in schizophrenia, and an inverse relationship of DTI fractional anisotropy (FA) values with positive symptom scores in association fibers, supporting a "disconnection" hypothesis of positive symptoms in schizophrenia.

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Diffusion Tensor Imaging in Schizophrenia

Cited by 114 publications

References 44 publications

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

Clinical and Neuropsychological Correlates of White Matter Abnormalities in Recent Onset Schizophrenia

Diffusion tensor imaging in schizophrenia: Relationship to symptoms

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