LAUSR

ABSTRACT Bipolar disorder (BD) is a highly disabling mental illness that affects approximately 1% of the global population. Cognitive capacity is a strong predictor of "everyday" functional outcome in BD and should thus be considered a key treatment target. Interventions to improve cognition have been largely unsuccessful, likely due to the substantial heterogeneity inherent to the illness. It is known that 40%-60% of people with BD have cognitive impairment, yet impairment is not "one size fits all"; in fact, the literature supports discrete cognitive subtypes in BD (e.g., intact, globally impaired, and selectively impaired). Gaining a better understanding of these cognitive subtypes, their longitudinal trajectories, and their biological underpinnings will be essential for improving patient outcomes. The prevailing hypothesis for the development of cognitive impairment in BD postulates a stepwise cumulative effect of repeated mood episodes causing wear-and-tear on the brain. However, a paucity of data supports this idea at the group level. We propose that studying heterogeneity longitudinally will allow for clearer delineation of the natural history of cognitive trajectories in BD. In sum, parsing heterogeneity in BD will allow us to identify causal mechanisms and optimize treatment at the level of the individual.