Compensatory Neural Networks for the Cognitive Control of Emotion in Youth at Risk for Bipolar Disorder

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PROJECT SUMMARY / ABSTRACT Offspring of parents with bipolar disorder (“at-risk youth”) are at increased risk for the development of psychopathology. Many of these at-risk youth have elevated mood lability, frequent and severe changes in mood state, which contributes to poor functioning and increases risk for mood disorder. However, not all individuals at familial risk develop psychiatric disorders, and in this project we explore the compensatory networks that could help to explain individual differences in risk. Several lines of evidence indicate that neural circuitry supporting working memory (WM) might act as such a compensatory network, and that better working memory capacity (WMC) in particular is associated with better emotion regulation and less mood lability. The objective of this project is to better understand the neural circuitry of mood lability, and to then assess potential compensatory neural mechanisms in youth at risk for bipolar disorder (BD). We propose to first assess differences between at-risk and healthy youth in the activation and functional connectivity (FxC) of ventral networks involved in cognitive reappraisal of emotion, and whether the individual differences in these networks correlate with degree of mood lability in the at-risk youth. We next evaluate if a greater WMC (and FxC of the central executive network, central to WM) might compensate for these ventral abnormalities, and thus might be associated with less mood lability in at-risk youth. To provide a probe of the directionality of this relationship, we conduct a pilot manipulation of WM training (5 weeks) in a subset of at-risk, labile youth. Identification of such a compensatory network in at-risk youth would provide a target for preventive measures in these youth, and pave the way for future studies investigating strategies for building resilience. In concert with this research plan, training goals will provide the Principal Investigator with a skillset necessary to further pursue this line of research: specifically, training in developmental cognitive neuroscience, the implementation of neuroimaging studies in pediatric populations, and sophisticated analysis of neuroimaging data. To obtain this training, the PI has assembled a mentorship team with expertise in relevant areas, most notably, her mentor Dr. Mary Phillips (neuroimaging in BD) and co-mentor Dr. Boris Birmaher (implementation of studies of youth with BD). She has also designed a detailed training plan, which includes formal collaborations with consultants, coursework, and workshops. Research and training activities will primarily occur at the University of Pittsburgh, an institution with a commitment to research in pediatric BD, as well as affective and cognitive neuroscience, and a strong track record for supporting the career development of junior faculty. This training will build on the PI’s existing background as a child psychiatrist with a strong knowledge of statistics and clinical neuroscience, to provide her will the necessary skills to become an independent investigator. Her long-term research goal is to better characterize the neurodevelopmental trajectory of BD in youth, and develop strategies for building resilience in those who are at risk for disorder.