Toward a comprehensive clinical staging model for bipolar disorder: Integrating the evidence

Objectives: To describe key findings relating to the natural history and heterogeneity of bipolar disorder (BD) relevant to the development of a unitary clinical staging model. Currently proposed staging models are briefly discussed, highlighting complementary findings, and a comprehensive staging model of BD is proposed integrating the relevant evidence. Method: A selective review of key published findings addressing the natural history, heterogeneity, and clinical staging models of BD are discussed. Results: The concept of BD has broadened, resulting in an increased spectrum of disorders subsumed under this diagnostic category. Different staging models for BD have been proposed based on the early psychosis literature, studies of patients with established BD, and prospective studies of the offspring of parents with BD. The overarching finding is that there are identifiable sequential clinical phases in the development of BD that differ in important ways between classical episodic and psychotic spectrum subtypes. In addition, in the context of familial risk, early risk syndromes add important predictive value and inform the staging model for BD. Conclusions: A comprehensive clinical staging model of BD can be derived from the available evidence and should consider the natural history of BD and the heterogeneity of subtypes. This model will advance both early intervention efforts and neurobiological research.