Diffusion Imaging of White Matter in Schizophrenia: Progress and Future Directions

Abstract

Diffusion tensor imaging (DTI) is a powerful tool for the in-vivo assessment of white matter microstructure. The application of DTI methodologies to the study of schizophrenia has supported and advanced the hypothesis of schizophrenia as a disorder of disrupted connectivity. In the context of impaired structural connectivity, the extended time frame of white matter development may offer unique opportunities for treatment that can capitalize on the neural flexibility that is still present in the period leading up to and after disease onset. Therefore, it is important to gain a clear understanding of white matter deficits and how they may emerge and change across the illness. However, while there is broad consistency in the findings of white matter deficits in patients with schizophrenia, there is also a great deal of variability in specific findings across studies. In this review, the aim is to move beyond summarizing case-control analyses, to consider the many factors that may impact DTI measures, to explain variability of findings, and to explore future directions for the field. The topics explored include ways to parse DTI patterns associated with different disease subtypes, ways in which novel and established treatments might interact with or enhance white matter, ways of dissociating developmental change from the disease process itself, and understanding the role of emerging analytic methodologies.

Cortical thickness of neural substrates supporting cognitive empathy in individuals with schizophrenia

“…There are several potential explanations for our negative findings. One possibility, is that schizophrenia is characterized by altered white matter pathways (Ellison-Wright and Bullmore, 2009; Karlsgodt, 2016), which may be accounting for the observed impairment in cognitive empathy in schizophrenia. Thus, Diffusion Tensor Imaging (DTI, e.g., fiber tractography) could be one possible tool to measure the complex integration of networks supporting cognitive empathy.…”

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“…The influence of cannabis on white matter volume in schizophrenia is weak 69,70 but DTI studies have shown both FA increases and decreases in cannabis-using patients with schizophrenia compared to non-using patients 28,71 . Previous analyses on the present study sample have demonstrated that familial predisposition for psychotic disorder is associated with greater cannabis-induced reduction in cortical thickness 72 . The current DTI results suggest that there is no marked effect of cannabis on microstructural white matter, as the controlling TBSS analyses for cannabis use did not change the results.…”

“…Secondary measures as radial diffusivity for the degree of myelination and axial diffusivity for axonal organization are more informative on the etiology of WM alterations in terms of myelin loss or axonal incoherence but as yet, less frequently reported. Lately, as it is apparent that the structure of neural tissue may be too complex to comprehend through a single diffusion tensor, the focus has shifted to more advanced WM measures derived from 'Free Water Imaging (FWI)' and the 'Permeability Diffusivity Index (PDI) 72 . Future studies examining WM integrity should implement these new diffusion methods to investigate the nature of the alterations in WM microstructure in more detail.…”

“…Longitudinal diffusion studies are scarce and have focused on changes in WM integrity during transition from UHR status to first-episode psychosis status 71 , or before and after short periods of AP treatment in first-episode 72 and late stage patients 73 .…”

“…Overall, the evidence suggests that AP medication, like other environmental and illness-related factors, may contribute to microstructural WM alterations (increase and decrease), The inconsistencies between the studies to date may have resulted from heterogeneous patient samples and differences in illness duration, AP type (first and second generation antipsychotics), cumulative lifetime AP dose assessment, and DTI processing techniques. Longitudinal (short, medium and long-term) studies using advanced diffusion imaging techniques, such as 'diffusion kurtosis imaging' or 'free water imaging' to examine respectively tissue characterization and putative signs for neuro-inflammation in more detail 72 , could help to further elucidate the impact of AP medication on neuronal (white matter) integrity.…”