Dr. John Krystal
Dr. John Krystal
Co-founder & Chief Scientific Advisor
John H. Krystal, MD is Robert L. McNeil, Jr., Professor of Translational Research; Professor of Psychiatry, Neuroscience, and Psychology; Chair of the Department of Psychiatry, Director of the NIAAA Center for the Translational Neuroscience of Alcohol, and Co-Director of the Yale Center for Clinical Investigation (CTSA) at Yale University; Director of the Clinical Neuroscience Division of the VA National Center for PTSD at VA Connecticut; and Chief of Psychiatry and Behavioral Health at Yale-New Haven Hospital. Dr. Krystal is a graduate of the University of Chicago, Yale School of Medicine, and Yale Psychiatry Residency Training Program.
Upon joining the Yale faculty (1988), Dr. Krystal established a research program on psychosis and cognition. Under his leadership, this program provided the first evidence in humans directly supporting the three core theories about schizophrenia/psychosis pathophysiology: NMDA glutamate receptor signaling deficits (1994), striatal dopamine hyperactivity (1996), and enhanced CB1 receptor signaling (2004). Beginning with ketamine studies, Dr. Krystal opened the field of human glutamatergic experimental psychopharmacology in psychiatry, characterizing parallels between circuit abnormalities produced by ketamine and those associated with schizophrenia using neuroimaging and computational neuroscience, and advancing the application of these research platforms in drug discovery. His studies contributed to the testing of novel alternatives to dopamine D2 receptor antagonism for schizophrenia treatment, including mGluR2/3 agonism (2005) and TAAR1 agonism (2020). This work was recognized by the Elkes Prize (ACNP), Dean Award (ACP), and Hoch Award (APPA), among other distinctions.
Dr. Krystal is best known for the discovery by his laboratory of the rapid antidepressant effects of ketamine in patients (2000), directly leading to FDA approval of the first novel antidepressant in 50 years (Esketamine, 2019). He and his collaborators then identified mechanisms in patients underlying these antidepressant effects: enhanced glutamate release (13C-MRS), restoration of cortical functional connectivity deficits (fMRI), restoration of synaptic density (PET) and novel mechanisms for enhancing or sustaining these effects via mTORC1 inhibition and glycine-site NMDA-R modulation. He also studied the neurobiology and treatment of alcoholism and PTSD. Most recently, he co-founded the National PTSD Brain Bank and co-led the first transcriptomic studies of PTSD. This work was recognized by honors including the Colvin Prize (BBRF), Anna-Monika Prize (A-M Foundation), Gold Medal Award (SOBP), and Ehrens Award (ACTS). He is a co-inventor of a number of patents that have been licensed or are being licensed to pharmaceutical or digital healthcare companies. In addition, he has contributed to the founding of two pharmaceutical companies (Biohaven Pharmaceuticals, Freedom Biosciences) and a digital mental healthcare company (Spring Health).
Dr. Krystal is a member of the U.S. National Academy of Medicine, fellow of the American Association for the Advancement of Science and co-chair of the Neuroscience Forum of the U.S. National Academies of Science, Engineering and Medicine. He chaired the NIMH Board of Scientific Counsellors and served on the National Advisory Councils for NIMH and NIAAA. As editor of Biological Psychiatry (IF=13.3), he oversaw the creation of a family of journals including BP: Cognitive Neuroscience and Neuroimaging (2015) and BP: Global Open Science (2020). He is past president of the American College of Neuropsychopharmacology (ACNP) and the International College of Neuropsychopharmacology (CINP).
