We propose to explore the neurobiological basis of Down syndrome, schizophrenia, and bipolar disorders using novel methods for measuring cortical neuroanatomy. We will develop and validate methods for measuring surface area, thickness, and thickness distribution of cortical structures, and use these methods in four subject groups: healthy individuals, and patients with Down syndrome, schizophrenia and bipolar disorder. We hypothesize that surface area and thickness measures will be more informative that conventional volume measures, and that patients with Down syndrome will have global cortical deficits. We believe that specific cortical regions will be affected in schizophrenia (heteromodal cortex) and bipolar disorder (entorhinal cortex). Although we focus here on three diseases, we believe that the methods that we will develop would be useful to researchers studying other diseases too. We plan to make our soDware (written in the JAVA language and thus portable to most popular computers including C's, Mac's and Unix-based systems) available on the laboratory's web site.