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Disruption of this connectivity can result in brain dysfunction manifested in impaired cognitive functioning and the development of clinical symptoms. White matter forms the basis of anatomical connectivity. Diffusion tensor imaging (DTI) is a useful tool for examining and quantifying white matter microstructure. Clinical research studies in alcoholism, HIV\u20101 infection, geriatric depression and schizophrenia using DTI have revealed abnormalities in white matter microstructure. The use of complementary imaging methods may be helpful in further characterizing these abnormalities. Other psychiatric disorders may also have white matter involvement amenable to study with DTI. Advances in acquisition and analysis methods will be necessary to further advance work in this field. The study of animal models and postmortem tissue may be helpful in elucidating the neurobiological underpinnings of abnormalities observed with DTI. 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