Research aimed at elucidating the underlying neurobiology and genetics of bipolar disorder, and factors associated with treatment response, have been limited by a heterogeneous clinical phenotype and lack of knowledge about its underlying diathesis. We used a survey of clinical, epidemiological, neurobiological, and genetic studies to select and evaluate candidate endophenotypes for bipolar disorder. Numerous findings regarding brain function, brain structure, and response to pharmacological challenge in bipolar patients and their relatives deserve further investigation. Candidate brain function endophenotypes include attention deficits, deficits in verbal learning and memory, cognitive deficits after tryptophan depletion, circadian rhythm instability, and dysmodulation of motivation and reward. We selected reduced anterior cingulate volume and early-onset white matter abnormalities as candidate brain …