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RESEARCH OPPORTUNITY AT LAUREATE INSTITUTE FOR BRAIN RESEARCH

Feb 18, 2010 in Notes from the President

More than one-third of the population will suffer from a neuropsychiatric disorder during their lifetime, which in many cases will result ultimately in death or disability. For some of these conditions, such as those associated with neurodegenerative illness, substantial progress has been made at understanding pathophysiology, yet effective treatments have remained elusive. For other brain-based conditions, such as the major psychiatric disorders, the converse has been true, as treatments that are partly effective have been discovered in the absence of certain knowledge about pathophysiology. Nevertheless, progress in developing more effective treatments for the major psychiatric disorders has reached an impasse, as too little is known about the neurobiology underlying these conditions to guide industry toward targets for drugs and biologicals capable of reducing further the clinical burden of these illnesses.

This slow pace of progress toward understanding the pathogenesis of neuropsychiatric illness contrasts with the rapid advances achieved in other areas of biomedical research, so that the neuropsychiatric disorders ranked increasingly higher as causes of disability. For example, the World Health Organization (WHO) currently ranks the most common neuropsychiatric illness, major depressive disorder (MDD), third in global disease burden in terms of disability-adjusted life years (DALYs), but first as a cause of disability per years of life lived (across all age groups). Moreover, within the next two decades the WHO estimates that MDD’s ranking in global disease burden (measured in DALYs) also will rise to first among all medical conditions. As another example, schizophrenia is among the most devastating illnesses encountered in the healthcare field, striking individuals in their youth or early adulthood, and causing sufficient disability that nearly one-half of the chronic-care medical beds within developed countries now are occupied by individuals suffering from schizophrenia. Yet little is known about the pathogenesis of MDD, schizophrenia, or other commonly disabling psychiatric conditions.

The development of biomedical research tools involving neuroimaging, proteomic, and genetic technologies has provided the means to advance understanding regarding the pathophysiology and etiology of neuropsychiatric disorders. Nevertheless, the amount of funding devoted to research aimed at bringing these technologies to bear in studies of psychiatric illness has been vastly lower than for research involving other categories of medical disease on a per-patient basis. Moreover, even as the amount of federal funding available for research has begun to decline in inflation-adjusted dollars, the disparities extant between funds spent on a per-patient basis for psychiatric disorders versus for other types of medical illness have widened rather than narrowed.

These limitations related to funding are compounded by the recent recognition that studies of psychiatric illness must become larger in scope with respect both to numbers of patients entered and to durations of time over which patients are followed. This recognition has grown partly out of recent advances in genetics, as it appears many of the neuropsychiatric disorders are caused by complex interactions between genetic variation and environmental factors that collectively alter the function of gene systems or signaling pathways that thus far remain unidentified. These observations raise the importance of research involving neuroimaging measures and other types of biomarkers that can identify the neural systems affected in common across individuals manifesting individual psychiatric disorders and can define the functional consequences of genetic risk factors for disease.

Recognizing this research opportunity and need, the W. K. Warren Foundation, having held a long interest in neuropsychiatric disease, pledged significant financial support toward the long-term, prospective study of neuropsychiatric disorders. In 2009 the Warren Foundation initiated the Laureate Institute of Brain Research (LIBR) in which potential biomarkers, including genetic sampling and neuroimaging studies of groups defined by partitioning of clinical phenotypes would be added to the longitudinal clinical studies to expand knowledge about the underlying pathogenetic features of mental disorders. The Foundation’s funding has provided a research facility that includes a state of the art magnetic resonance imaging (MRI) center and an extensive computing network.

To address the complexity of neuroscience research, guiding principles in the development of LIBR have been to emphasize multi-disciplinary and multi-institutional involvement, as well as to gather young, proven talent from diverse fields, who share a common vision and are committed to interacting in collaborative research. LIBR presently has nearly 40 full-time scientific, clinical, or administrative faculty and staff. In addition, the LIBR program catalyzed the formation of a “Quadrangle of Neuroscience Research”, which brought together researchers from Tulsa University (TU), Oklahoma University School of Community Medicine (OUSCM) and Oklahoma Medical Research Foundation (OMRF), all of which have made commitments of individual and collaborative research activities, into a consortium arrangement. The studies undertaken by this consortium will facilitate the dissection of specific neuropsychiatric diseases and their related genetic or environmental influences that dictate responses to unique pharmacological or psychological therapies. The consortium already has active collaborative relationships with TU’s highly ranked Department of Mathematics and Computer Science, which also includes a new Institute of Bioinformatics and Computational Biology (IBCB), and training relationships for graduate students and post-doctoral fellows with OUSCM, which is expanding as an academic medical center that will emphasize clinical neuroscience as an overarching research activity. Finally, OMRF has become an outstanding biomedical research institution capable of basic science studies of the complex molecular genetics of human disease and animal models of human disease, as well as studies related to drug-design, pharmacokinetics and targeted gene disruption. Scientists at LIBR also have established highly fruitful research collaborations with geneticists, neuropsychologists, neurobiologists, and imaging scientists at the National Institutes of Health, Cambridge University, and Washington University. Working together we and our collaborators aim to leverage scientific discovery as the means to help persons throughout the world who suffer from neuropsychiatric illness.

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