This is a renewal of the protocol entitled "Children of Bipolar Parents: A High-Risk Follow-up Study" (NIMH #60952) also known as the Bipolar Offspring Study (BIOS). BIOS is aimed at investigating the early behavioral phenotypes, syndromal/subsyndromal psychiatric disorders, circadian and sleep patterns, negative life events, psychosocial factors, and inherited traits that are associated with the development of bipolar disorder (BP) in children. Since the single largest risk factor for the development of BP is a positive family history of BP, to accomplish BIOS aims, we have been recruiting offspring of parents with BP and comparing them with offspring of community parents selected at random and matched by age, sex, race, and neighborhood. As of 5/2005, BIOS has recruited 387 offspring of 213 parents with BP and 252 offspring of 133 control parents with a retention rate of 95 percent. At our current rate of recruitment, by 6/2006 BIOS will have a total of 550 offspring of 300 BP parents and 350 offspring of 200 control parents. We are starting to show higher rates of BP, depression, and anxiety disorders, subsyndromal BP symptomatology, and certain behavioral phenotypes between the offspring of BP and community control parents even after controlling for demographic factors, parental non-BP psychopathology, and within-family correlations. Thus, the very existence of this sample, the largest of its kind to date, clearly underscores the success of BIOS in ascertaining and retaining a large cohort of offspring of parents with BP and controls. Since most of the BIOS sample is entering an age of high-risk for developing mood disorders, we propose to continue to follow this large sample for 5 more years. Children will be continued to be evaluated face-to-face every other year by raters who are blind to parental diagnosis using standardized assessments. In addition, DNA from saliva samples will be collected. We hypothesize that offspring of BP vs. offspring of controls will show: 1) higher rates of BP, depression, disruptive, anxiety, and substance use disorders; 2) higher rates of mood lability, irritability, aggression, sleep problems, and impulsivity; and 3) different trajectories of maturational changes in circadian variables and sleep patterns. Within the offspring of BP parents, the onset of mood disorders will be predicted by the combined effects of variables (e.g., behavioral phenotypes, genetics, puberty). Parents with BP will present different circadian patterns than control parents and circadian polymorphisms found to be associated with BP among the adult participants will be preferentially transmitted from BP parents to their offspring. This unique prospective study will have important implications for early-detection, intervention, and prevention of childhood-onset BP. Moreover, as described in detail in the proposal, BIOS is becoming a national resource for other neurocognitive, imaging, genetic, and psychometric studies.
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