Christopher Pittenger, MD, PhD
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Overview
STUDIES OF BASAL GANGLIA FUNCTION IN MICE. The basal ganglia, consisting of the striatum (caudate-putamen) and related subcortical structures, have historically been considered to have primarily motor functions; but it has become increasingly clear that they are also involved in a variety of cognitive and affective processes. Disruption of normal basal ganglia function is seen in a variety of neuropsychiatric conditions, such as obsessive-compulsive disorder, Tourette syndrome, and drug addiction.
The striatum has been divided into distinct functional regions, though both the anatomical subdivisions and the functions with which they are associated remain approximate and subject to debate. The ventral striatum, consisting of the nucleus accumbens and related structures, has a well-documented role in reward and reward-driven learning, and has been extensively researched in the context of drug addiction. The dorsal striatum (caudate and putamen, in primates) is thought to have a role in the formation of motor and cognitive patterns and in forms of implicit learning, including the formation of habits.
The Pittenger laboratory is focused on better understanding the mechanisms of dorsal striatum-dependent habit-like learning, and of the consequences of its perturbation in various neuropsychiatric conditions. We conduct our researches primarily in mice, which allows us to take advantage of sophisticated reverse genetic techniques to perturb the striatal circuitry in molecularly precise ways and to target specific striatal subregions and neuronal subtypes.
MODELING PSYCHIATRIC DISEASE. We are applying this technology to model neuropsychiatric conditions affecting the striatum, especially Tourette syndrome. This represents a third focus of the laboratory. Modeling psychiatric disease in animals has proven enormously challenging, because etiology is often obscure and symptomatology is often difficult to translate to non-verbal species. We believe that the development of valid models hinges on a sufficient degree of understanding of pathophysiology to ensure validity when translating to animals.
Fortunately, studies at Yale and elsewhere are beginning to produce such understanding in the case of Tourette syndrome. We are using genetic methods to produce putative models of Tourette syndrome based both on post-mortem findings and on genetic insights . These animals are then being tested in a variety of behavioral assays to assess their recapitulation of Tourette syndrome phenomenology, explore secondary and tertiary consequences of the initial manipulations, and investigate the response to both established and novel medications.
A FOCUS ON TRANSLATIONAL RESEARCH: NEW MEDICATIONS FOR OBSESSIVE-COMPULSIVE DISORDER (OCD). The final focus of the Pittenger laboratory is also translational. Dr. Pittenger is Director of the Yale OCD Research Clinic, where he has found glutamate-modulating medications to be of potential benefit in the treatment of patients with obsessive-compulsive disorder (a condition in which basal ganglia dysfunction is implicated). We are examining the behavioral and molecular effects of such glutamate-modulating drugs in animals, to better understand their role in patients with this and related conditions. As new animal models of disorders of the basal ganglia, like OCD, become available, we hope to use this translational approach to advance our understanding both of the normal role of the basal ganglia in behavior and its perturbation in disease, and to develop new generations of therapeutics for the psychiatric population.
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Academic Achievements & Community Involvement
Clinical Care
Overview
Chris Pittenger, MD, PhD, earned his MD and PhD degrees from Columbia University, where his graduate work was done with Nobel Prize recipient Eric Kandel. He returned to Yale University, his undergraduate alma mater, for residency and research training in psychiatry in 2003. He joined the faculty as an Assistant Professor in 2007 and is now Elizabeth Mears and House Jameson Professor of Psychiatry, Professor of Psychology and in the Child Study Center, and Deputy Chair for Translational Research in the Department of Psychiatry.
Dr. Pittenger has always been fascinated by the question of how the brain, a complex but ultimately a physical structure, creates thought, feeling, consciousness, and other aspects of the mind. As a psychiatrist he is additionally focused on how these processes go wrong—how brain dysregulation leads to dysregulated cognition, emotion, and behavior and to mental suffering, and how advancing our understanding of these relationships can guide us to new strategies to alleviate that suffering.
Much of his work has focused on obsessive-compulsive disorder and Tourette syndrome and on the cortico-basal ganglia circuitry that is implicated in their pathophysiology. More recently Dr. Pittenger has co-founded the Yale Program for Psychedelic Science, focusing on understanding how molecules like psilocybin and LSD can teach us about brain and behavior and may lead to new treatments for a range of neuropsychiatric pathology. He is also one of the founding Directors of the Yale Center for Brain and Mind Health, which seeks to bridge disciplines and levels of analysis to bring new therapeutics to individuals suffering from disorders of the mind and brain.
Dr. Pittenger's research and clinical work have been acknowledged by a number of prestigious awards, including grant funding from the National Institute of Mental Health, the National Institute of Neurological Disease and Stroke, NARSAD, the Tourette Syndrome of America, the Doris Duke Charitable Trust, and other organizations. He has won a number of awards, including from the National Institute of Mental Health, the Society for Neuroscience, the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American College of Psychiatrists.
He is a member of the Scientific Advisory Board of the International OCD Foundation and Chair of both their Grant Review Committee and their Annual Research Symposium Planning Committee. He is a Fellow of the American College of Neuropsychopharmacology, the American Psychiatric Association, and the American Neurological Association.
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