NEUROCOGNITIVE, NEUROIMAGING AND GENETIC PERSPECTIVE OF HUMAN DEVELOPMENT AND PSYCHOPATHOLOGY

Abstract

BackgroundThe search for quantitative endophenotypes that can serve as biomarkers of risk for major psychiatric disorders requires the availability of large community samples that are genotyped as well “deep phenotyped”. The link from molecular processes to behavior requires understanding brain structure and function relevant to neurocognitive domains affected in neuropsychiatric disorders. The goal of the Philadelphia Neurodevelopmental Cohort (PNC) is to provide such a resource for the scientific community. MethodsParticipants in the PNC were about 9,500 youths, ages 8-21, who presented to Children’s Hospital of Philadelphia network who were genotyped and underwent a comprehensive screen for psychopathology using a computerized adaptation of the KSADS supplemented by collateral information obtained from a parents and electronic medical records. All participants received a computerized neurocognitive battery (CNB) that measures executive function, episodic memory, complex cognition, social cognition and sensorimotor speed. A subsample of 1600 also received multimodal neuroimaging that includes structural MRI, diffusion tensor imaging (DTI), resting state cerebral blood flow measure with ASL and connectivity with BOLD and two activation tasks. ResultsAcross measures, significant effects were evident for age group, indicating development, as well as sex differences. Both general effects of psychopathology and more specific effects were observed on the neurocognitive measures as well as the multimodal brain parameters. We have begun to find genetic links and are developing methodology for joint phenomic-genomic analysis. ConclusionsThe PNC provides a rich dataset with information sensitive to development and psychopathology. Initial analyses underscore the importance of sex difference and indicate that development is associated with dynamic changes in brain parameters of structure, function and connectivity. Understanding the links between behavior and brain parameters is prerequisite for establishing bridges between genomics and neuropsychiatric phenotypes.