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

Abstract

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 firstdegree 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.

Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study

“…6 Both a neurodevelopmental model, 7,8 implying that WM alterations are present before disease onset and a postonset progression model, indicating that structural brain abnormalities progress over time after disease onset, have been proposed. 9,10 In support of the neurodevelopmental model, several cross-sectional DTI studies have revealed microstructural WM alterations in frontotemporal and -parietal connections in first-degree relatives without symptoms, 11,12 in clinical high-risk populations before onset, 13,14 and in patients with early onset psychosis. 15 Indeed, the lifetime trajectory of WM alterations in schizophrenia suggests higher percentages of WM loss in the first years of the illness, implicating altered neurodevelopment.…”

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

“…Evidence from functional magnetic resonance imaging has shown that modulation of fronto-parietal connectivity during working memory processing was gradually reduced from healthy controls to ARMS subjects and then to first-episode patients (FEP) [14], suggesting that fronto-parietal connectivity changes in psychosis evolve along a dynamic trajectory, emerging before disease onset and developing with ongoing illness. DTI studies have shown reduced FA in the SLF in patients with FEP [15], as well as in subjects at clinical [16,17] or genetic high-risk of psychosis [18,19] (for a review see [11]). DTI studies have also observed increased MD in the SLF of genetic [18] and clinical high-risk individuals [17].…”

“…DTI studies have shown reduced FA in the SLF in patients with FEP [15], as well as in subjects at clinical [16,17] or genetic high-risk of psychosis [18,19] (for a review see [11]). DTI studies have also observed increased MD in the SLF of genetic [18] and clinical high-risk individuals [17]. …”

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

“…In addition, COS is a rare and more severe form of AOS and has a more pronounced genetic risk (Asarnow and Asarnow, 1994;Asarnow and Forsyth, 2013;Asarnow et al, 2001;Nicolson and Rapoport, 1999). There have been extremely few DTI studies in this population; Moran et al (2015) and Clark et al (2011) found decreased FA in COS patients, and Ashtari et al (2007) found decreased FA in early onset schizophrenia (defined as onset before the age of 18) patients.…”