Bipolar disorder is a severe heritable psychiatric illness affecting 1% of the general population. The age of onset is generally in the late teenage years or early adulthood. Very little is known about specific risk factors that influence the incidence and age of onset of this disorder. In 1988 the NIMH established a Genetics Initiative in bipolar disorder with the goal of identifying susceptibility genes; this collaboration has identified several hundred families with multiple cases of bipolar disorder. As 3 of the initial collaborating sites 'Indiana University, Johns Hopkins University, and Washington University at St Louis) we are now proposing to assess and follow adolescents, ages 12 -18 years, in these families. This will include offspring and nieces and nephews. This """"""""at risk"""""""" group will be compared to a matched set of community comparison subjects. 300 study subjects and 300 controls will be studied using established diagnostic instruments (KSADS-PL) for the adolescents and the parents (DIGS). Other instruments to assess behavior, temperament, family environment, and substance use will be employed. The data will be stored in a database developed to facilitate longitudinal studies of clinical variables. Analyses will compare potential risk factors among the high-risk group and the controls. Annual follow-up of the high- risk group will begin in the second year of the study. It is hypothesized that 3 groups will be identified: 1) adolescents with behavioral symptoms or disorders who manifest early-onset bipolar disorder; 2) adolescents with anxiety symptoms or disorders who manifest later-onset bipolar disorder; and 3) adolescents with minor mood symptoms or disorders who manifest later-onset unipolar or bipolar disorder. The ethical implications of this research will be studied by examining the effects of participation and the effect on self-esteem due to high- risk status.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Avenevoli, Shelli A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
Zip Code
Hulvershorn, Leslie A; King, Jennifer; Monahan, Patrick O et al. (2017) Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk? Compr Psychiatry 78:130-139
Wilcox, Holly C; Fullerton, Janice M; Glowinski, Anne L et al. (2017) Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts. J Am Acad Child Adolesc Psychiatry 56:1073-1080
Fullerton, Janice M; Koller, Daniel L; Edenberg, Howard J et al. (2015) Assessment of first and second degree relatives of individuals with bipolar disorder shows increased genetic risk scores in both affected relatives and young At-Risk Individuals. Am J Med Genet B Neuropsychiatr Genet 168:617-29
Monahan, P O; Stump, T; Coryell, W H et al. (2015) Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity. Psychol Med 45:2181-96
Nurnberger Jr, John I; McInnis, Melvin; Reich, Wendy et al. (2011) A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders. Arch Gen Psychiatry 68:1012-20
Agrawal, A; Nurnberger Jr, J I; Lynskey, M T (2010) Item response modeling of DSM-IV mania symptoms in two representative US epidemiological samples. Psychol Med 40:1549-58