Transdiagnostic Neural Mechanisms Underlying Dimensions of Negative Affectivity in Depression and Anxiety

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ABSTRACT There is growing recognition that strict distinctions between clinical psychiatric disorders such as anxiety and depression, on the one hand, and more stable dispositions to experience negative emotions (negative affectivity), on the other, fail to capture the true nature of psychopathology. We argue that by examining specific dimensional phenotypes that cut across depression and anxiety disorders, we will be better able to identify the neurobiological processes that are specifically associated with an individual's distress and dysfunction – a critical step for developing more effective, targeted treatments. Negative affectivity is a broad dimension that underlies depression and anxiety and is associated with enormous public health consequences. One of the specific facets of negative affectivity, excessive self-consciousness, may represent a dimensional phenotype that is closely aligned with a specific pattern of dysfunction in neural mechanisms that can lead to difficulties regulating emotional responses. Excessive self-consciousness refers to the tendency to feel shame, humiliation, and inadequacy. Our preliminary data suggest that it is strongly associated with altered functioning in self-related processing neural regions and in regions responsible for emotion regulation, over and above acute psychiatric symptoms. Furthermore, our findings suggest that excessive self-consciousness is strongly associated with specific types of real-world interpersonal problems. The primary goals of this project are to test a novel model of neural dysfunction during emotion regulation associated with excessive self-consciousness and to examine the real-world consequences of that dysfunction. To achieve these goals, 125 young adults (18-25 years old) with at least mild symptoms of depression or anxiety will be recruited. In addition, 75 demographically matched, psychiatrically healthy individuals will be recruited to ensure that we capture the full range for all of the dimensions of interest. Participants will complete clinical and neuroimaging assessments, as well as 6- and 12-month follow-up assessments that will include weeklong daily diary protocols of real-world functioning. The project will examine 1) whether excessive self-consciousness is associated with abnormal functioning in self-related processing regions; 2) whether excessive self-consciousness is associated with abnormalities in the functioning of the emotion regulation circuit; and 3) whether abnormalities in these neural systems prospectively predict psychiatric symptoms and poorer interpersonal and work functioning 6 and 12 months later. The aims of the project match well with the strategic goals of the National Institute of Mental Health, and the results of this study have the potential to describe specific neurobiological mechanisms associated with excessive self-consciousness – a dimensional phenotype that cuts across anxiety and depressive disorders. Future work will aim to develop personalized treatments to target the neural mechanisms identified in this study in order to reduce distress and improve functional outcomes.