This is a request for an ADAMHA RSDA (Level II). The broad objective of this proposal is to facilitate and sustain the Applicant's development as a career scientist in psychiatric genetics. Building upon the experience gained during the tenure of the Level I RSDA, this objective will be attained in the following manner: (a) Research Plans; Recent advances in statistical and molecular genetics, and in diagnostic concepts of mental illness, hold much promise for unraveling the genetic mechanisms that underlie subtypes of affective illness. This, in turn, would have major implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of these disorders. The search for specific gene markers, using linkage analysis techniques, is considered a powerful strategy in human genetics. Accordingly, the aims of this research are: (i) To perform linkage studies with DNA markers in pedigrees of bipolar affective probands; (ii) Should linkage be established, to characterize the genetically linked cases on clinical/biological measures in an attempt to define homogeneous subsets of the disorder. Long range goals will include the assessment of linked markers as risk predictors and the localization and characterization of the defective gene (or genes). The possibility of employing the linkage strategy in schizophrenia research will also be explored. (b) Development and Professional Growth; The experience to be gained during the conduct of this research will foster the Applicant's scientific growth. In addition, further training coupled with consultation and collaboration on gene marker research (molecular genetics) and on methods of genetic analysis will be sought, with the aim of refining and advancing the Applicant's scientific knowledge. Specialized training in some aspects of these areas will be considered.
