Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia

Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Journal of Psychiatric Research (Impact Factor: 3.96). 02/2011; 45(7):980-8. DOI: 10.1016/j.jpsychires.2011.01.006
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The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high-resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.

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    • "SZ showed lower FA in left pericingulate, right middle/superior frontal, perilentiform and right dorsal pontine, compared to UHR. UHR individuals showed lower FA in left lingual and insular gyri as well as right deep frontal gyri, compared to SZ. 4 C. Dacquino et al. / Clinica Chimica Acta xxx (2015) xxx–xxx Please cite this article as: Dacquino C, et al, Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types, Clin Chim Acta (2015), studies in people at genetic risk for psychosis [83] [84]. Studies of firstepisode and drug-naïve patients have shown more severe involvement of the anterior white matter, such as the anterior thalamic radiations [85] [86] and the internal capsule [86] [87], which are associated with severity of clinical features and clinical outcome. "
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    • "Another limitation of our study was the small sample size. However, our sample size was similar to most other studies of schizophrenia patients and relatives (e.g., Camchong et al., 2009; Clark et al., 2011; Knochel et al., 2012). To compare to previous literature and for future meta-analyses, we calculated Cohen's d effect sizes for the classical whole-tract means. "
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    • "In the present study, the structural measures demonstrated generally decreased structural integrity of the bilateral dorsal and ventral pathways in schizophrenia (Table 3). This finding was consistent with previous DTI studies using region-based or voxel-based measurements, which reported reduced FA in the bilateral arcuate fasciculi (Phillips et al., 2009; Catani et al., 2011; de Weijer et al., 2011), higher MD in the bilateral inferior fronto-occipital fasciculi (Clark et al., 2011), and reduced integrity of the ventral pathway (Kubicki et al., 2011). Prior research has demonstrated that the dorsal pathway is involved in semantic processing. "
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