Neurodevelopmental Patterns of Social Reactivity in Youth at Increased Familial Risk for Bipolar I Disorder

PROJECT SUMMARY Altered ventrolateral prefrontal cortex (VLPFC) function and brain connectivity are implicated in emotional dysregulation and the emergence of bipolar disorder. However, our understanding of the development of VLPFC brain networks prior to bipolar disorder onset is limited. In contrast, we have more comprehensive

knowledge of healthy adolescent brain development, specifically the profound influence of peers on emotionally responsive brain regions and long-term mental health. This F32 research project aims to gather feasibility and pilot data to support our central hypothesis that during late development (age 14-21), youth with

a family history of bipolar I disorder (high-risk) will exhibit altered maturation of VLPFC function and connectivity during negative social interactions compared to youth without a family history (low-risk), which will be closely associated with measures of emotional reactivity and dysregulation. My long-term career objective is

to become an expert in utilizing neuroimaging techniques to assess bipolar disorder risk and develop stress resilience interventions. During this research project, I aim to enhance my neuroimaging expertise, academic presence and knowledge in the neurodevelopment of bipolar disorder through this F32 training and hands-on

research. To test our central hypothesis, we will pursue two specific aims. Firstly, we will investigate the neurodevelopmental maturation patterns in VLPFC activation and connectivity during peer ostracism in high- risk compared to low-risk youth. Specifically, we will compare group differences in the relationship between

development and VLPFC response and connectivity with emotionally responsive (e.g., subgenual anterior cingulate) and cognitively oriented brain regions (e.g., dorsolateral prefrontal cortex) during peer ostracism. Secondly, we will investigate the relationship between VLPFC function and connectivity during peer ostracism

and emotional reactivity/regulation in both high and low-risk groups. We posit that, for both groups, VLPFC activity and connectivity with medial prefrontal cortex, insula, striatum, and thalamus will be associated with cyberball task distress and the ability to regulate negative emotions more generally. Additionally, we predict

that a VLPFC connectivity and other lateral prefrontal brain regions will be associated with greater emotional resilience only in high-risk individuals, namely, less emotional reactivity and dysregulation. This study will investigate emotional control brain networks within a developmental framework, utilizing a participant cohort of

180 youth. By studying these networks before the onset of secondary disease effects and employing age relevant social tasks, we aim to obtain valuable pilot data for publication while refining our hypotheses for future research and grant submissions. Findings from this study will advance our understanding of the

neuropathophysiological mechanisms preceding bipolar disorder onset, a step toward earlier intervention during this dynamic period of emotional and social development.