Emerging biosignature of brain function and intervention in pediatric bipolar disorder

Pediatric bipolar disorder (PBD) is a complex illness with a chronic course, requiring multiple medications over the longitudinal course of illness, with limited recovery and high relapse rate. Beyond the placebo controlled trials of monotherapy, there is an increased need to understand how each medication influences regions of affective and cognitive circuitry function by normalization or deployment of alternative circuitry regions. Functional studies are beginning to unravel the improved function in the fronto-limbic and fronto-temporal affective circuitry, and based on the paradigm administered, also in the interfacing cognitive fronto-striato-temporo-parietal regions. Treatment studies illustrated a pattern of improvement in functional activity consistently among the affective ventrolateral and medial prefrontal regions, and variably in the cognitive dorsolateral prefrontal cortex. While there is decreased activity in amygdala with treatment for mania or depression among patients with PBD, there appears to be residual increased amygdala activity regardless of response, relative to healthy controls, suggesting a trait-like abnormality. Parallel biochemical abnormalities in magnetic resonance spectroscopic studies and fronto-limbic activity in magnetic resonance imaging studies of brain function at baseline provide maiden data on predicting outcome. This preliminary cohort of studies that probed the hypothesized circuitries underlying specific symptom constructs, coupled with futuristic paradigms and analytic methods, serve as a guidepost to generate the next generation of studies and build on the emerging biosignature towards specific treatment targets for personalized medicine in PBD.