Novel approaches to the study of postmortem brain in psychiatric illness: old limitations and new challenges

Biological psychiatry has made significant advances through the development of postmortem studies, animal models, and studies with living humans. Although these approaches each have advantages and disadvantages, the postmortem field is undergoing a significant shift toward more complex and informative methodologies. In the first part of this review, we summarize the long-standing methodologic challenges facing this field. In the second part of the article, we discuss the innovative approaches being used for postmortem studies, including laser capture microdissection and subcellular fractionization. These techniques will permit scientists working in the postmortem field to ask and answer the largest possible questions, providing new targets for drug discovery and improved treatments for severe mental illness.