White matter diffusivity and microarchitecture among schizophrenia subjects and first-degree relatives

Abstract

Background Impairments in structural and functional connections are demonstrated in schizophrenia. Certain disconnectional patterns may be biomarkers of elevated risk for schizophrenia. Convergent examination of multiple diffusion parameters and cognitive performance better illustrates pathophysiological significance of such disconnectional patterns. Methods Diffusion Tensor Imaging data on 39 early-course schizophrenia subjects, 21 adolescent/young adult first-degree relatives (FDR) of schizophrenia subjects and 29 healthy controls (HC) were examined for threshold-free clusters of fractional anisotropy (FA) and radial diffusivity (RD) differences correcting for multiple comparisons. Regression models examined the variance contributed by anisotropy differences, age and sex. Group-wise differences on sustained attention, verbal memory and executive functions were examined and correlated with diffusivity measures controlling for age and sex. Results Schizophrenia subjects showed significantly decreased FA and increased RD in the forceps minor and superior longitudinal fasciculus (SLF) compared to HC. FDR showed decreased forceps minor FA compared to HC, and decreased SLF RD compared to HC and schizophrenia subjects. Quantitative RD differences were 2–3 fold higher compared to FA. Besides, forceps minor RD was inversely correlated with sustained attention in schizophrenia. Conclusions Schizophrenia and FDR subjects show different patterns of white matter diffusivity compared to HC. While forceps minor changes may be a disease marker, SLF changes may be risk markers. In addition, RD may be a more robust risk marker than FA.

Diffusion tensor imaging in first degree relatives of schizophrenia and bipolar disorder patients

“…This study allowed non-psychotic psychiatric disorders in the relative group. Another recent study using TBSS also found decreased FA in forceps minor and decreased RD in the SLF and forceps minor in relatives compared to control (Prasad et al, 2014). …”

“…All but two of the fourteen studies found some abnormalities in the relative group compared to healthy controls (Boos et al, 2013; Camchong et al, 2009; Clark et al, 2011; Goghari et al, 2014; Hao et al, 2009; Hoptman et al, 2008; Knöchel et al, 2012a, 2012b; Muñoz Maniega et al, 2008; Phillips et al, 2011; Prasad et al, 2014; Skudlarski et al, 2013). Ten of these studies found decreased FA (Camchong et al, 2009; Clark et al, 2011; Hao et al, 2009; Hoptman et al, 2008; Knöchel et al, 2012a, 2012b; Muñoz Maniega et al, 2008; Phillips et al, 2011; Prasad et al, 2014; Skudlarski et al, 2013), four found increased FA (Boos et al, 2013; Goghari et al, 2014; Hoptman et al, 2008; Knöchel et al, 2012a), one found increased ADC (Knöchel et al, 2012b), and one found decreased RD (Prasad et al, 2014).…”

“…13 studies compared DTI measures in unaffected relatives of SZ patients and healthy controls (Boos et al, 2013; Camchong et al, 2009; Clark et al, 2011; DeLisi et al, 2006; Domen et al, 2013; Goghari et al, 2014; Hao et al, 2009; Hoptman et al, 2008; Knöchel et al, 2012a, 2012b; Muñoz Maniega et al, 2008; Phillips et al, 2011; Prasad et al, 2014) while 8 did the same in unaffected relatives of BD patients and healthy controls (Chaddock et al, 2009; Emsell et al, 2013; Frazier et al, 2007; Linke et al, 2013; Mahon et al, 2013; Sprooten et al, 2013, 2011; Versace et al, 2010). One study used DTI in comparing unaffected relatives of both SZ and BD patients and healthy controls (Skudlarski et al, 2013).…”

“…Ten of these studies found decreased FA (Camchong et al, 2009; Clark et al, 2011; Hao et al, 2009; Hoptman et al, 2008; Knöchel et al, 2012a, 2012b; Muñoz Maniega et al, 2008; Phillips et al, 2011; Prasad et al, 2014; Skudlarski et al, 2013), four found increased FA (Boos et al, 2013; Goghari et al, 2014; Hoptman et al, 2008; Knöchel et al, 2012a), one found increased ADC (Knöchel et al, 2012b), and one found decreased RD (Prasad et al, 2014). In general, the findings were of reduced FA.…”

Topographic deficits in alpha-range resting EEG activity and steady state visual evoked responses in schizophrenia

“…Several studies have reported connectivity issues between frontal and occipital cortices (Fornito et al, 2011;Liu et al, 2012;Cheng et al, 2015), including fractional anisotropy deficits of inferior and superior longitudinal fasciculus pathways (Lener et al, 2015;Prasad et al, 2015). Therefore, although from EEG recordings we can only indirectly infer the cortical sources underlying scalp recorded activity, the current findings of decreased alpha resonance in frontal regions may reflect resonance deficits particularly in the frontal cortex, perhaps mediated by thalamo-cortical abnormalities, in addition to dysfunction in connectivity between occipital and frontal cortices preventing alpha oscillations from reaching frontal regions.…”