PI: James Knowles
Institution: State University of New York


Dr. Knowles leads the R01 project “Addition of OCD to the Genomic Psychiatry Cohort” that expands the Genomic Psychiatry Cohort (GPC) by ascertaining and enrolling 5,000 patients suffering from Obsessive-Compulsive Disorder (OCD) and performing a genome-wide association study (GWAS) on 5,000 OCD patients and 5,000 already ascertained and genotyped OCD-free matched controls. In addition to the GWAS data, Dr. Knowles also collects MRI data on a subset of the OCD patients using the cutting-edge protocol from the Human connectome Project. Using these connectome imaging data and the genetic risk factors assessed from the large-scale GPC study, our goal is to elucidate the genetic and neural basis of OCD. To this end, connectome imaging data from 20 OCD patients and 20 controls have been collected together with behavior assessments based on the Yale-Brown Obsessive Compulsive Scale (YBOCS). In this service project, Dr. Knowles will collaborate with the LONIR P41 to examine these sophisticated imaging data and study the neurocircuitry and genetic basis in OCD. The connectomics tools from TRD2 will be critical to reconstruct the fiber pathways related to OCD such as the cortico-striatal-thalamic-cortical (CSTC) networks from the multishell diffusion MRI acquired with HCP protocol. After that, various connectivity measures on these pathways will be evaluated to study group differences and correlation with behavior measures. The intrinsic surface mapping tools from TR&D3 will be applied to study the structural changes in OCD patients. The novel mapping algorithms from TR&D3 will allow the holistic mapping of the striatum surfaces that enables the detailed comparisons of striatal morphometry at corresponding locations across groups. The surface mapping algorithms will also allow the analysis of both cortical and other sub-cortical morphometry in the OCD patients as compared to normal controls. All the imaging measures provided by the LONIR software tools will be used for quantifying their genetic basis with a polygenic score calculated from the GWAS data. Overall these innovative analyses will help us better understand the neurocircuitry affected in OCD and their potential genetic basis. The results from this will pave the way for future large-scale OCD imaging projects.