We have developed a method for automated probabilistic reconstruction of a set of major white-matter pathways from diffusion-weighted MR images. Our method is called TRACULA (TRActs Constrained by UnderLying Anatomy) and utilizes prior information on the anatomy of the pathways from a set of training subjects. By incorporating this prior knowledge in the reconstruction procedure, our method obviates the need for manual interaction with the tract solutions at a later stage and thus facilitates the application of tractography to large studies. In this paper we illustrate the application of the method on data from a schizophrenia study and investigate whether the inclusion of both patients and healthy subjects in the training set affects our ability to reconstruct the pathways reliably. We show that, since our method does not constrain the exact spatial location or shape of the pathways but only their trajectory relative to the surrounding anatomical structures, a set a of healthy training subjects can be used to reconstruct the pathways accurately in patients as well as in controls.National Institute for Biomedical Imaging and Bioengineering (U.S.) (Pathway to Independence Award EB008129)National Institutes of Health (U.S.). Blueprint for Neuroscience Research (U01-MH093765)National Center for Research Resources (U.S.) (P41-RR14075 and U24-RR021382)National Institute for Biomedical Imaging and Bioengineering (U.S.) (R01-EB006758)National Institute on Aging (R01-AG022381)National Center for Complementary and Alternative Medicine (U.S.) (RC1-AT005728)National Institute of Neurological Disorders and Stroke (U.S.) (R01-NS052585, R21-NS072652, and R01-NS070963)Ellison Medical Foundation. Autism & Dyslexia Project