The early course of bipolar disorder: From genetic risk to illness onset

Bipolar disorder (BD) is a severe, heterogeneous psychiatric illness for which there is a lack of information about the origins and early natural history. As BD has strong genetic underpinnings, longitudinal studies of the offspring of carefully diagnosed parents is an important strategy to describe the early clinical course and to study factors influencing illness onset in those predisposed. With previous funding, we have identified a large unique cohort of offspring of bipolar parents classified by the parent response to lithium treatment, which is a strategy to identify more homogeneous subgroups. We were able to describe for the first time the early clinical stages of BD. Clinical staging has tremendous potential to advance early diagnosis and treatment, as well as to inform neurobiological research. In related work, we identified factors associated with the risk of BD including: temperament, current life stress and abnormalities in cortisol, a stress-sensitive hormone. We now propose to extend our longitudinal high-risk study in order to characterize the early clinical stages of BD and investigate the influence of risk factors in illness development. This high-risk study is the largest and longest in duration of its kind worldwide. Results from this study will form the basis of a working model of BD and will provide a clinical staging framework that will inform the way we diagnose, treat and study BD.