FUNCTIONAL NEUROANATOMY OF SOCIAL AND PERCEIVED INTERNAL THREAT IN ANXIOUS YOUTH AT HIGH-RISK FOR BIPOLAR DISORDER

The purpose of this K23 application is to support my short-term career objectives of acquiring multimodalneuroimaging, neurocomputational, biostatistical, and theoretical social cognitive knowledge in the study ofanxiety and emotion regulation in youth at high-risk for bipolar disorder (BD). Longitudinal evidence suggeststhat youth at high-risk for BD that develop any mood disorder experience an anxiety disorder as an earlyantecedent. Anxiety is therefore an important symptom in the developmental trajectory of BD. One of thelargest sources of anxiety in youth is the quality of social relationships, which greatly influence youth'sperceived quality of life. However, little is known about the neural underpinnings of social cognition in youth athigh-risk for BD or how everyday social interactions affect anxiety and emotion regulation, which is a hallmarkcharacteristic of BD. In a previous pilot study (P.I. Roybal, American Academy of Child and AdolescentPsychiatry/Lilly Pilot Research Award), I showed differences in brain activation and functional connectivitybetween youth with BD relative to healthy controls (HC) when both groups experienced a functional magneticresonance imaging (fMRI) social rejection task. I applied this fMRI social rejection task to youth at high-risk forBD (P.I. Roybal, Hogg Foundation for Mental Health). The research proposed here will add to the sample sizeof this high-risk group (HR) as it proposes to use the same fMRI social rejection task and add on an fMRI taskevaluating perceived internal threat subsequent to social rejection. Behavioral assessments and fMRI will beused to assess functional neuroanatomical correlates in the HR group. Our hypotheses predict that the HRgroup will have functional neural deficits relative to HC during a social rejection task that involve regions salientto social rejection, specifically subgenual anterior cingulate cortex and anterior insula, but also will involvelimbic areas not typically seen in social rejection, specifically the amygdala and hippocampus. We hypothesizethat within the HR group, hyperactivation and abnormal connectivity observed during the social rejection taskwill correlate with subsequent anxiety felt after experiencing social rejection. We will also examine the effectsof social rejection on internal threat cues that affect mood. We hypothesize the HR group will exhibit greateramygdala activation and weaker functional connectivity between amygdala and prefrontal cortex, a structuretheorized to regulate the amygdala, relative to HC. Within the HR group, abnormal activation and connectivitywill be correlated with the ability to emotionally self-regulate. Both treating youth with and at high-risk for BDand having basic neuroimaging experience have laid a solid foundation for me to achieve my training goalsand complete this study. The proposed integrated research, mentorship, and didactic training programs,combined with the outstanding research environment at the University of Texas Health Science Center at SanAntonio, will foster my long-term career objective of being a leading expert in multimodal social cognitive neuralmodels as they relate to anxiety and emotion regulation in children at high-risk for BD.