Kimoto et al, 2015

The overall objective of the Translational Neuroscience Program (TNP), directed by David A. Lewis, MD, is to understand the neurobiological basis for complex human cognitive and emotional functions, and the manner in which alterations in the brain give rise to the types of disturbances in these functions that characterize psychiatric disorders. Disorders of particular interest include schizophrenia, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, addiction and Alzheimer’s disease with psychosis. In pursuit of this goal, Program scientists seek to translate clinical observations into hypotheses about the biological mechanisms involved in a disease process that can be tested in the more tractable conditions of the laboratory in order to guide the identification of molecular targets for drug development. Indeed, the principal motivation for these studies is the acquisition of the knowledge needed to develop novel approaches for improving the treatment and prevention of these disorders.

The research strategies utilized by the Translational Neuroscience Program are designed to dissect the disease process of interest. Program investigators seek to explore how certain etiological factors, or causes of an illness, can unleash pathogenic mechanisms that produce pathological disturbances in the brain, and how these brain disturbances give rise to the pathophysiological processes that alter brain function and are manifest as a particular clinical syndrome. Understanding pathophysiology is critical to the rational development of new treatments that can reverse these processes, resulting in the amelioration of the signs and symptoms of an illness. Similarly, understanding pathogenesis is essential for the development of secondary forms of disease prevention.

Because brain pathology occupies the center point of the series of events that lead to major psychiatric disorders, Program research activities focus on identifying the nature of the brain disturbances in these illnesses. Any observed brain alteration may represent any of the following five “Cs”: 1) an upstream cause related to the disease process, 2) a deleterious consequence of a cause, 3) a compensation, resulting from either a cause or consequence, that attempts to restore homeostasis, 4) a factor that is frequently comorbid with the disease process, or 5) a confound associated with the tissue quality or technical approach. By identifying the nature or type of each observed alteration, Program scientists are able to dissect and develop models of the disease process that guide investigations into disease pathogenesis and pathophysiology, enabling the identification of novel targets and the development of interventions directed against those targets.