Diffusion Imaging Biomarkers for risk, onset and outcome in schizophrenia

While schizophrenia has been hypothesized to be a dis-connection syndrome, the exact biological nature of white matter abnormalities in this disease is still unknown. Furthermore, while multiple publications report white matter "abnormalities" in schizophrenia, those findings to date have not lead to further understanding of schizophrenia etiology or new developments in pharmacological treatment. This is primarily because imaging measures remain nonspecific to the underlying microstructural pathology, and changes observed with MRI have been viewed as an ongoing consequence of gray matter pathological processes, thus not worth pursuing the possibility of white matter involvement further. In this application we propose to go beyond measuring "white matter integrity". We hypothesize that white matter in schizophrenia may be compromised by several, distinct pathological processes that can be observed at different stages of the disease (some even before the presence of clinical symptoms), and thus could potentially constitute biomarkers of risk, onset, and outcome of schizophrenia. The overall goal of this proposal is to use Diffusion MRI, along with the newest MRI acquisition and analysis methods, and to apply them to distinct schizophrenia and schizophrenia related populations (both retrospectively as well as prospectively).