Reduced frontolimbic functional connectivity in psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder

Motivation: Although youth with attention-deficit/hyperactivity disorder (ADHD) with a family history of bipolar I disorder (BD) are at increased risk for developing BD, associated neurofunctional mechanisms remain understood. Goal(s): To investigate the differences in functional connectivity (FC) between ventrolateral prefrontal cortex (VLPFC) and amygdala (AMY) among ADHD youth with (‘high-risk’, HR) and without (‘low-risk’, LR) a BD family history and healthy controls (HC). Approach: gPPI analysis was conducted to assess the VLPFC-AMY FC in response to unpleasant emotional stimuli. Results: Both LR and HR exhibited lower right VLPFC-left AMY FC compared to HC, and HR had even lower FC compared with LR. Impact: ADHD in conjunction with BD family history showed blunted emotion-generated right VLPFC-left AMY FC compared with ADHD youth without a BD family history and healthy youth, and may therefore represent a central biomarker that is relevant to BD risk progression.