The Clinical and Translational Neuroscience Branch continues to make advances on several fronts in order to delineate the neurochemical, neurogenetic, and neuropsychological contributions to neural systems function and development relevant to mental illness. We have embarked on data collection for two unprecedented scientific resources: first, a unique multimodal neuroimaging dataset in adults that includes neuropsychological testing, extensive dopaminergic PET imaging as well as MR spectroscopy, functional and structural MRI; and, second, a longitudinal, neurodevelopmental dataset that incorporates structural and functional magnetic resonance-based brain imaging, and, in conjunction with the Section on Behavioral Endocrinology, precise, state-of-the-art endocrinological measurements of pubertal status. These comprehensive ongoing data acquisition efforts have resulted in a growing repository of integrated information about the brain, which will permit both novel analyses synthesizing disparate but interrelated indices of neurochemical (e.g., dopamine, GABA, and glutamate) functioning and discovery of critical genetic and endocrinological factors guiding neurodevelopment. This work has already begun to yield important insights into social neurocognitive processes, which inform models of abnormal processing of social cues in neuropsychiatric conditions such as schizophrenia, autism and Williams syndrome. In a series of multimodal experiments, we have taken advantage of magnetoencephalography, positron emission tomography and magnetic resonance imaging methods to first identify heretofore unappreciated links between midbrain dopamine stores and how social neural networks react to viewing emotional faces, then dissect how specific types of such brain activity modulate over time as expressions emerge on a viewed face, and most recently, discover genetic association between the Williams syndrome region gene, GTF2I, and relationships between trait neuroticism and social neural activity. Other recent efforts have focused on defining the impact of gene variants associated with schizophrenia and general cognitive functioning and has begun to evaluate new hypotheses about how sequelae of common genetic variation intersects with the biology of mental illness. We have successfully tied the heritable intermediate phenotype first described by this group prefrontal inefficiency during the working memory N-back task to a promising schizophrenia risk variant in the SCN2A gene. Collaborative studies have now confirmed genetic associations between variation in the SCN2A gene and both cognitive ability and interregional brain connectivity in a large cohort of healthy individuals. In parallel, work this year has uncovered links between a genetic locus previously associated with educational attainment and broad cognitive ability. We also remain engaged in studies characterizing the genetic determinants of key neurochemical phenotypes (i.e., MRS- and PET-based signals) that have been linked with neuropsychiatric illness. Finally, ongoing work is aimed at understanding the underlying structure of our neural systems and cognitive-behavioral measurements. For instance, in view of increasingly prominent views that dimensions of psychopathology are extremes of more typical dispositional variation, we have now undertaken analyses of characterological and personality disorder assays of a large cohort of healthy individuals unfettered by confounds inherent in clinical populations. We have preliminarily identified several prominent dimensions Negative Affect, Detached, and Egocentric that complement leading personality theories and may lend insight into latent personality trait structure regardless of diagnostic thresholds.
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