Stephen Strakowski, MD, The University of Texas at Austin, Chair and Professor, Dept of Psychiatry

Bipolar I disorder is defined by the occurrence of mania, although depression occurs in >80% of affected individuals, as do a myriad of other affective, cognitive, behavioral and neurovegetative symptoms. These symptoms wax and wane often in different combinations over time so that many individuals with bipolar I disorder are not correctly diagnosed for up to 10 years. This clinical presentation suggests that in bipolar I disorder healthy neural processes that modulate affective, cognitive and risk-reward behaviors are disrupted, creating an unstable, dynamic psychiatric illness. Moreover, mania typically emerges in adolescence or young adulthood. Studies of bipolar I disorder have largely converged to a median age at onset in the range of 15-25 years old across a variety of survey methods, countries and ethnic groups. Once it occurs, mania is a strongly predictive phenotype; more than 80% of affected individuals will experience lifelong recurrent affective episodes. Additionally, long-term outcome studies suggest that the early course of bipolar disorder is progressive. Specifically, periods of euthymia progressively shorten after each of the first several affective episodes ultimately settling into a ‘stably unstable’ course of illness. Moreover, most individuals experience affective, anxiety, cognitive and behavioral symptoms for several years prior to the first manic episode. Together, the age at onset, predictive phenotype and progressive clinical course suggest that bipolar I disorder results from failure to develop healthy neural emotional systems in the transition from adolescence into young adulthood. The cerebellum has been implicated as both part of these important networks and also to be abnormal early in the course of illness. In this presentation we will review clinical and neuroimaging data to conceptualize a neurodevelopmental model of bipolar disorder; within this model, the potential role of the cerebellum, and the need to better understand its function in this context, will be discussed.