Testing frameworks for personalizing bipolar disorder.

The hallmark of bipolar disorder is a clinical course of recurrent manic and depressive symptoms of varying severity and duration. Mathematical modeling of bipolar disorder holds the promise of an ability to personalize diagnoses, to predict future mood episodes, to directly compare diverse datasets, and to link basic mechanisms to behavioral data. Several modeling frameworks have been proposed for bipolar disorder, which represent competing hypothesis about the basic framework of the disorder. Here, we test these hypotheses with self-report assessments of mania and depression symptoms from 178 bipolar patients followed prospectively for 4 or more years. Statistical analysis of the data did not support the hypotheses that mood arises from a rhythmic process or multiple stable states (e.g., mania or depression) or that manic and depressive symptoms are highly anti-correlated. Alternatively, it is shown that bipolar disorder could arise from an inability for mood to quickly return to normal when perturbed. This latter concept is embodied by an affective instability model that can be personalized to the clinical course of any individual with chronic disorders that have an affective component.