Bipolar disorder (BD) remains 1 of the 10 most debilitating illnesses worldwide.¹ Neuroimaging investigations have aimed to identify functional and structural neural circuitry abnormalities that may reflect pathogenetic processes of the disorder,² particularly neural abnormalities implicated in mood dysregulation, a key symptom of BD. Although few, these studies^2-4 provide some evidence for functional abnormalities in neural systems that may be associated with the following key symptoms: (1) abnormally increased activity in a subcortical limbic-centered system underlying emotion processing and (2) abnormally decreased activity in a system that includes ventral and dorsal prefrontal cortices underlying cognitive control processes. These findings require replication, but they provide a basic framework to guide examination of brain structure in subjects with BD.

Most psychiatric disorders in youth include behavioral dysregulation disorders (DDs) that are often associated with emotional problems (eg, attention-deficit/hyperactivity disorder [ADHD]; disruptive behavior disorders [DBDs], including conduct disorder and oppositional defiant disorder); and emotional DDs that are often associated with behavioral problems (eg, depressive disorder, bipolar spectrum disorder [BPSD], and anxiety disorder). Given the overlap of symptoms and their high comorbidity, however, psychiatric disorders in youth pose challenges for diagnosis and treatment, increasing the use of “not otherwise specified” diagnoses.^1-4 Although diagnostic manuals represent the consensus standard for psychiatric diagnosis, research needs to establish a groundwork for a future diagnostic system based on underlying pathophysiologic processes by using frameworks that may cut across conventionally defined diagnoses.⁵