DESCRIPTION (provided by applicant): The Human Connectome Project (HCP) was initiated to accelerate progress in understanding the organization of the human brain. To accomplish this goal, the original HCP Washington-University-Minnesota and MGH/Harvard-UCLA Projects have focused on acquiring and sharing data relevant to structural and functional connectivity in 1200 healthy twins and their siblings. The main aims have been to use advanced 3T imaging to develop advanced data acquisition and scanning sequences, to develop novel algorithms for post-processing of white matter fiber structure and brain connectivity, and to develop novel graphical techniques for brain connectomes. The purpose of the new funding opportunity announcement, PAR-14-281 for Connectomes Related to Human Diseases (U01), is to build upon the original HCP by extending it to the study of human brain diseases in order to acquire the same high quality data as in the original HCP, but with the goal of accelerating knowledge of brain diseases in a manner heretofore not possible. Importantly, progress has been slow and frustrating in translating knowledge of the brain to new and more effective treatments for human brain diseases such as severe mental disorders. In fact, severe mental disorders, which include psychotic disorders, are brain diseases that are not only devastating because they result in severe disruptions that occur early in life, but, for many, the course of illness is progressive, leading to chronic debilitation and early mortality. Thus the need to accelerate knowledge of dysfunctions in structural and functional brain connectivity in these disorders, and to translate this knowledge to treatment, is critical. The primary goal of the proposed "Human Connectome Project on Early Psychosis" is to acquire high quality data consistent with data acquired by the original HCP. To this end, we will acquire imaging data on Prisma 3T magnets at two sites, one in Boston and one in Indianapolis, using the HCP Lifespan Prisma protocol. This imaging protocol was developed to be of similar high quality to the original HCP, but with reduced scan time, the latter important in a psychosis cohort. We will also use behavioral measures from the HCP as well as additional measures specific to early psychosis. We will acquire blood to be stored at the Rutgers University Cell and DNA Repository (RUCDR)(Aim 1), and we will use the Washington University HCP post-processing pipeline to process imaging data (Aim 2). Additionally, we will include new imaging tools for signal drop detection, multi-tensor tractography, diffusion magnetic resonance imaging (dMRI) models, i.e., free-water imaging, and a new harmonization protocol for diffusion images (Aim 3). We will also perform, as a representative example, a study comparing brain networks of affective and non-affective psychosis groups with controls (Aim 4). The main goals are thus to acquire high quality imaging, behavioral, cognitive, and genetic data on an important cohort of early psychosis patients, in a manner consistent with the HCP, which will be made available to the research community for future studies. Such data will provide a unique opportunity to characterize the pathological substrates of early psychosis.

PUBLIC HEALTH RELEVANCE: The main goal of the proposed "Human Connectome Project for Early Psychosis" is to acquire high quality imaging, behavioral, clinical, cognitive, and genetic data on an important cohort of early psychosis patients, in a manner consistent with the original Human Connectome Project, where data from this project will be made available to the research community for future studies. We focus on early psychosis (both affective and non- affective psychosis), within the first 3 years of the onset of psychotic symptoms. This is a criticl time period when there are fewer confounds such as prolonged medication exposure and chronicity, and when early intervention strategies will be most effective, prior to the progression that often leads to debilitating and chronic illnesses, to great suffering, and to an enormous public health problem and economic burden. The data acquired will make it possible to identify disruptions in neural connections in early psychosis that likely underlie both brain function and dysfunction, and these data can be linked to behavioral, cognitive, and other measures, consistent with the goals of this funding initiative. Such an approach will lead not only to a bettr understanding of neural network disruptions in psychotic illnesses but will also lead to more targeted treatment interventions early in the course of illness to prevent the cascade of progression to chronicity where changes in the brain are likely not reversible.