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William Eaton's research interests encompass two complementary areas: using epidemiologic methods to elucidate the risk factors, natural history, and outcomes of major mental disorders, and adopting sociologic approaches to explore unusual behaviors often classified as psychiatric disorders. His work in psychiatric epidemiology includes global studies on the incidence and progression of schizophrenia using psychiatric case registers, as well as investigating the link between autoimmune diseases and conditions like autism, schizophrenia, and bipolar disorder. Through his involvement in the Baltimore Epidemiologic Catchment Area (ECA) Follow-Up, Eaton has explored the interplay between mental and physical health, notably finding that major depressive disorder predicts conditions like type 2 diabetes, heart attack, stroke, and breast cancer. Currently, he is collaborating on the ECA project's latest phase, linking mental health data to the National Death Index for the most extensive U.S.-based population study of its kind.