Objective: The authors reviewed studies of child and adolescent offspring of bipolar (BP) parents. Findings from these studies are critically discussed with respect to methodological issues that can inform future designs. Methods: A Medline search was performed to identify studies that examined child and adolescent offspring of BP parents. Publications were excluded if they did not separate offspring of BP parents from offspring of major depressive disorder or schizoaffective parents ('affective offspring') or did not separately analyze data from child- and adolescent-age versus adult offspring. Results: Seventeen studies fit these review criteria. Rates of mood disorders in child and adolescent offspring of BP parents ranged from 5 to 67% compared with rates in offspring of healthy volunteers of 0-38%. Rates of non-mood disordered psychopathology ranged from 5 to 52% in offspring of BP parents and from 0 to 25% in offspring of healthy volunteers. Rates of mood disorders and of other psychopathology were increased in offspring of BP parents compared with offspring of healthy volunteers in all of the eight studies that included a comparison group of offspring of healthy volunteers. Conclusions: Studies suggest that children (less than or equal to 21 years) of BP parents are at increased risk for developing mood and other disorders (e.g., disruptive, anxiety). Therefore, additional investigations are clearly warranted. In the context of current research on diagnosis, assessment, longitudinal course and comorbidity of childhood mania, the following suggestions for the design of future studies should be considered: 1) Phenotypic specification of bipolar manifestations (e.g., BP-I, BP-II, BP-NOS) in child/adolescent offspring and in bipolar parents themselves. 2) Control groups that are pediatric-age relevant and thus include attention-deficit hyperactivity disorder. 3) Assessments that include items for prepubertal mania and for onsets and offsets of all occurrences of symptoms and of environmental factors (e.g., life events) in offspring and in parents so that trajectories of overlap and sequence between child and parental mania can be investigated. 4) These detailed onsets and offsets of symptoms are also necessary to investigate prodromal manifestations of mania in the offspring. 5) Unaffected offspring present a unique opportunity to study pre- and postmorbid cognitive and physiological endophenotypes and structural and functional brain abnormalities. Findings from offspring studies will be crucial to inform research on the development of early intervention and prevention strategies.
