Dr. Anne L. Glowinski is an instructor in child and adolescent psychiatry and a postdoctoral fellow in psychiatric genetic epidemiology at the Washington University School of Medicine. This is a revised application for a Mentored Clinical Scientist Development Award (K08) to support 5 years of investigation of the familial transmission of youth suicidal behavior. The Candidate will be mentored by Dr. Andrew Heath, an internationally renowned behavior geneticist, and Dr. Richard Todd, a child psychiatrist with advanced expertise in molecular genetics and neurobiology. The research funded by this award will be in keeping with the 1999 Surgeon General's call to heed youth suicide. The Candidate's preliminary analyses of twin and family data sets suggest the existence of genetic and environmental susceptibilities to suicidal behavior. Major Depressive Disorder (MDD) has been found in many studies, to be the disorder most firmly associated with suicidal behavior, yet the precise etiological relationship of suicidal behavior and depression is unclear. Also, familial factors, such as parental alcoholism appear to substantially increase the risk of youth suicidal behavior. Using a program of comprehensive secondary data analysis of existing twin-family data sets and new data, collected in a community sample of adolescent female and male twins, the Candidate will examine: 1) Epidemiological, clinical and other characteristics associated with youth suicidal behavior; 2) Familial aggregation of suicidal behaviors; 3) Genetic and environmental influences on youth suicidal behavior; 4) The relationship between genetic influences on suicidal behavior and genetic factors involved in the familial transmission of depression and other psychiatric disorders in adolescents; 5) The contribution of parental alcoholism to suicidal behavior is adolescents (including genotype by environment interaction effects) and the mediators involved in this contribution. In carrying out this plan of research, and through formal coursework, tutorials and selected readings, the Candidate will acquire expertise in conducting twin-family studies, analyzing complex twin-family data and will additionally gain knowledge in other areas upon which she anticipates her career as a clinician scientist will draw in the future including: Developmental neurobiology, molecular genetics, genetic association and linkage analysis.