PROJECT SUMMARY: Circuits and Molecules Core The Circuits and Molecules (C&M) Core of the Center for Neuroscience-based Mental Health Assessment and Prediction (NeuroMAP) in Phase II will support Research Project Leaders (RPLs) and Pilot Project Investigators (PPIs) by overseeing the acquisition, storage, and analysis of biological samples and neuroimaging data. The first goal of the C&M Core is to accelerate the RPL and PPI projects by (a) providing the necessary expertise in neuroimaging and molecular biology to ensure the success of NeuroMAP projects and (b) aiding in the formulation of new aims and hypotheses based on common core data elements (CDE) to make R-level grant applications more competitive. The second goal of C&M Core is to develop self-sufficiency so that it can ultimately serve as a resource for the broader geographical region. To achieve this goal, the C&M Core will develop a detailed business plan with cost estimates to support sustainability beyond the CoBRE. The C&M Core will work together with the Recruitment and Assessment Core and the Data Management and Statistics Core to support the NeuroMAP theme: the identification and validation, via an experimental approach, of targetable disease-modifying processes (DMPs) in mood and anxiety disorders. During Phase I, a set of CDE was established across all projects and provided a balance between the research goals of the individual RPL projects and secondary data analyses for PPIs. During that Phase, more than 350 neuroimaging assessments were obtained consisting of a standard structural MRI, diffusion tensor imaging, a resting state MRI, and several functional MRI tasks. Similarly, blood samples from over 350 participants were collected to measure a range of circulating inflammatory mediators. In Phase II, the C&M Core will work with the Recruitment and Assessment Core to collect a new imaging and laboratory data set that can be used by RPLs to extend their projects and PPIs to identify new DMPs. The imaging and laboratory measures were selected to delineate process dysfunctions by individuals with mood and anxiety disorders in the (a) Negative Valence domain i.e., how individuals respond to aversive contexts, (b) Positive Valence domain i.e., how individuals respond to positive contexts and (c) Interoception domain i.e., the processing of internal bodily signals to affect behavior. These measures will be optimized in Phase II. Advanced sequences to measure myelin content and neuroinflammation (restricted diffusion imaging) will be added to the Circuit component while the Molecules component will focus on the measurement of microRNA and proteins from astrocyte- enriched extracellular vesicles (EVs), building on our recent publications in this area. The C&M Core will be led by Co-Directors, Drs. Rohan and Savitz with the support of Ms. Arterbury and Drs. Burrows and Misaki. Drs. Savitz and Burrows (molecules component) will also liaise closely with Dr. Teague, director of the Integ...