John Krystal, MD
Robert L. McNeil, Jr. Professor of Translational Research and Professor of Psychiatry, of Neuroscience, and of PsychologyCards
Additional Titles
Co-Director, Yale Center for Clinical Investigation
Chair, Psychiatry
Physician-in-Chief of Psychiatry, Yale New Haven Hospital
Director: NIAAA Center for the Translational Neuroscience of Alcoholism
Director, Clinical Neuroscience Division, VA National Center for PTSD
Publications Overview
- 937 Publications
- 81,577 Citations
- 224 Yale Co-Authors
Administrative Support
Additional Titles
Co-Director, Yale Center for Clinical Investigation
Chair, Psychiatry
Physician-in-Chief of Psychiatry, Yale New Haven Hospital
Director: NIAAA Center for the Translational Neuroscience of Alcoholism
Director, Clinical Neuroscience Division, VA National Center for PTSD
Publications Overview
- 937 Publications
- 81,577 Citations
- 224 Yale Co-Authors
Administrative Support
Additional Titles
Co-Director, Yale Center for Clinical Investigation
Chair, Psychiatry
Physician-in-Chief of Psychiatry, Yale New Haven Hospital
Director: NIAAA Center for the Translational Neuroscience of Alcoholism
Director, Clinical Neuroscience Division, VA National Center for PTSD
Publications Overview
- 937 Publications
- 81,577 Citations
- 224 Yale Co-Authors
Administrative Support
About
Titles
Robert L. McNeil, Jr. Professor of Translational Research and Professor of Psychiatry, of Neuroscience, and of Psychology
Co-Director, Yale Center for Clinical Investigation; Chair, Psychiatry; Physician-in-Chief of Psychiatry, Yale New Haven Hospital; Director: NIAAA Center for the Translational Neuroscience of Alcoholism; Director, Clinical Neuroscience Division, VA National Center for PTSD
Biography
Dr. Krystal is a leading expert on the neurobiology and treatment of psychiatric disorders. His work links psychopharmacology, neuroimaging, molecular genetics, and computational neuroscience to study the neurobiology and treatment of disorders including alcohol use disorder, depression, PTSD, and schizophrenia. He is best known for leading the discovery of the rapid antidepressant effects of ketamine in depressed patients.
Within Yale, he chairs the Department of Psychiatry, serves as Chief of Psychiatry for the Yale-New Haven Health System, co-leads the Yale Center for Clinical Investigation (CTSA), co-directs the NIAAA Center for the Translational Neuroscience of Alcohol, and leads the Clinical Neuroscience Division of the National Center for PTSD (VA).
In addition to his roles at Yale, he serves as editor of Biological Psychiatry, Vice-President of the Scientific Council for the Brain and Behavior Research Foundation, as a Scientific Advisory Board member of Aligning Research to Impact Autism, and in numerous other advisory capacities for government agencies, academia initiatives, private foundations, and pharmaceutical/biotechnology companies. He also co-founded Freedom Biosciences, a company devoted to addressing the limitations of current rapid-acting antidepressants.
Dr. Krystal previously co-chaired (2018-2024) the Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine. He also served on the Department of Defense Psychological Health Advisory Committee, the National Advisory Councils for the National Institute of Mental Health and the National Institute on Alcohol Abuse and Alcoholism, and the NIMH Board of Scientific Counselors (chair, 2005-2007). He has led the American College of Neuropsychopharmacology (president, 2012), and International College of Neuropsychophamacology (president, 2016-2018).
Appointments
Psychiatry
ChairDualPsychiatry
ProfessorPrimaryDepartment of Psychology
ProfessorSecondaryNeuroscience
ProfessorSecondary
Other Departments & Organizations
- Abraham Ribicoff Research Facilities
- Adult Psychiatry
- Center for the Translational Neuroscience of Alcohol
- Clinical Neuroscience Research Unit
- Dean's Workshops
- Department of Psychology
- Diabetes Research Center
- Division of Neurocognition, Neurocomputation & Neurogenetics
- Interdepartmental Neuroscience Program
- MR Core
- Neuroscience
- Neuroscience Research Training Program (NRTP)
- Neuroscience Track
- Psychiatry
- Yale Biomedical Imaging Institute
- Yale Center for Clinical Investigation (YCCI)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Medicine
- Yale Ventures
- Yale-Drug use, Addiction, and HIV prevention Research Scholars (DAHRS)
Education & Training
- Residency
- Yale University School of Medicine (1988)
- MD
- Yale University (1984)
- BA
- University of Chicago, Behavioral Sciences (1980)
Research
Overview
Medical Research Interests
ORCID
0000-0001-6952-1726
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Deepak Cyril Dsouza, MBBS, MD
Ralitza Gueorguieva, PhD
Joel Gelernter, MD
Ilan Harpaz-Rotem, PhD, ABPP
Ismene Petrakis, MD
Chadi Abdallah, MD
Schizophrenia
Stress Disorders, Post-Traumatic
Alcoholism
Veterans
Psychiatry
Neuroimaging
Publications
2025
Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD
Hwang A, Skarica M, Xu S, Coudriet J, Lee C, Lin L, Terwilliger R, Sliby A, Wang J, Nguyen T, Li H, Wu M, Dai Y, Duan Z, Srinivasan S, Zhang X, Lin Y, Cruz D, Deans P, Huber B, Levey D, Glausier J, Lewis D, Gelernter J, Holtzheimer P, Friedman M, Gerstein M, Sestan N, Brennand K, Xu K, Zhao H, Krystal J, Young K, Williamson D, Che A, Zhang J, Girgenti M. Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD. Nature 2025, 1-11. PMID: 40533550, DOI: 10.1038/s41586-025-09083-y.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPost-traumatic stress disorderPrefrontal cortexDorsolateral prefrontal cortexHuman prefrontal cortexTraumatic stress responseHuman brainDepressive disorderStress disorderTrauma exposureCell type-specific contextRegulatory mechanismsGABAergic transmissionCell-type clusteringCell type-specific mannerMolecular regulatory mechanismsGlucocorticoid signalingGene expression changesChromatin dynamicsCredible variantsDisordersTranscriptional regulationEpigenetic dataCortexPersistent effectsPolygenic disorderOptimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans
Fischer I, Overstreet C, Cabrera-Mendoza B, Qiu D, Krystal J, Polimanti R, Gelernter J, Pietrzak R. Optimism moderates the relationship between inflammatory polygenic risk and major depressive disorder in U.S. Military veterans. The World Journal Of Biological Psychiatry 2025, 26: 189-198. PMID: 40343713, DOI: 10.1080/15622975.2025.2498352.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsMajor depressive disorderU.S. military veteransPolygenic risk scoresDepressive disorderMilitary veteransMajor depressive disorder riskPsychosocial moderatorsMDD screeningLow optimismPolygenic riskHigher optimismNationally representative sampleTrauma burdenPredisposition to inflammationStandard deviation increaseUK BiobankGenetic riskPathway-based analysisVeteransIncreased oddsRepresentative sampleRisk scoreMedical conditionsInflammatory biomarkersChronic inflammationAcute Alcohol‐Induced Changes Measured With Metabotropic Glutamate Receptor 5 Positron Emission Tomography
Raval N, Smart K, Angarita G, Miller R, Huang Y, Krystal J, Carson R, Cosgrove K, O'Malley S, Hillmer A. Acute Alcohol‐Induced Changes Measured With Metabotropic Glutamate Receptor 5 Positron Emission Tomography. Addiction Biology 2025, 30: e70031. PMID: 40309934, PMCID: PMC12044519, DOI: 10.1111/adb.70031.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsBlood alcohol levelsAlcohol challengeEffects of acute alcohol consumptionPeak blood alcohol levelsLaboratory alcohol challengeNon-displaceable binding potentialMetabotropic glutamate receptor 5Acute alcohol challengeGlutamate releaseAlcohol-induced changesGlutamate receptor 5Alcohol consumptionAcute alcohol consumptionMGluR5 availabilityPET scansSocial drinkersEthanol doseAlcohol effectsBrain regionsAcute alcoholBinding potentialCortical regionsClinically relevant dosesDrinking occasionsAlcohol levels533. Bold Signal Can Capture Individual Variability in Spatial Working Memory Deficits Induced by Ketamine
Rahmati M, Moujaes F, Purg N, Fonteneau C, Santamauro N, Tamayo Z, Repovs G, Preller K, Anticevic A, Fineberg S, Murray J, Krystal J, Cho Y. 533. Bold Signal Can Capture Individual Variability in Spatial Working Memory Deficits Induced by Ketamine. Biological Psychiatry 2025, 97: s317. DOI: 10.1016/j.biopsych.2025.02.772.Peer-Reviewed Original Research478. Cross-Site Quality Assessment of Data From a Pharmacologic Neuroimaging Trial Targeting Working Memory Neural Circuits in Schizophrenia
Zharyy C, Fonteneau C, Rahmati M, Price A, Gil R, Govil P, Grinband J, Gur R, Haubold N, Heffernan Z, Lu J, Mayer M, Ranganathan M, Santamauro N, Tamayo Z, Van Snellenberg J, Wolf D, Group T, Anticevic A, Lieberman J, Kantrowitz J, Abi-Dargham A, Gur R, Krystal J, Cho Y. 478. Cross-Site Quality Assessment of Data From a Pharmacologic Neuroimaging Trial Targeting Working Memory Neural Circuits in Schizophrenia. Biological Psychiatry 2025, 97: s294. DOI: 10.1016/j.biopsych.2025.02.716.Peer-Reviewed Original ResearchConcepts598. Impact of the mGluR5 Antagonist, Mavoglurant, on P300 Response in an Auditory Oddball Task in in Individuals With a Positive or Negative Family History of Alcoholism
Richardson A, Stone A, Pearlson G, Krystal J, DeMartini K, O'Malley S, Mubeen M, Pancholi K. 598. Impact of the mGluR5 Antagonist, Mavoglurant, on P300 Response in an Auditory Oddball Task in in Individuals With a Positive or Negative Family History of Alcoholism. Biological Psychiatry 2025, 97: s345. DOI: 10.1016/j.biopsych.2025.02.837.Peer-Reviewed Original ResearchSocial Homeostasis: A New Paradigm for Mental Health Diagnosis and Treatment
Allsop A, Tye K, Krystal J. Social Homeostasis: A New Paradigm for Mental Health Diagnosis and Treatment. Biological Psychiatry 2025, 97: 932-935. PMID: 40316377, DOI: 10.1016/j.biopsych.2025.03.007.Peer-Reviewed Original ResearchAltmetricA multi-omic approach implicates novel protein dysregulation in post-traumatic stress disorder
Wang J, Liu Y, Li H, Nguyen T, Soto-Vargas J, Wilson R, Wang W, Lam T, Zhang C, Lin C, Lewis D, Glausier J, Holtzheimer P, Friedman M, Williams K, Picciotto M, Nairn A, Krystal J, Duman R, Young K, Zhao H, Girgenti M. A multi-omic approach implicates novel protein dysregulation in post-traumatic stress disorder. Genome Medicine 2025, 17: 43. PMID: 40301990, PMCID: PMC12042318, DOI: 10.1186/s13073-025-01473-1.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsPost-traumatic stress disorderDorsolateral prefrontal cortexPsychiatric disordersAutism spectrum disorderPrefrontal cortexDepressive disorderStress disorderGamma-aminobutyric acidGenome-wide association studiesPTSD brainsGenome-wide measurementsStudies of postmortem brainsSubgenual prefrontal cortexDisabling psychiatric disorderMultiple psychiatric disordersPrefrontal cortical areasPTSD casesHuman brain studiesBrain regionsSpectrum disorderGABAergic processesPostmortem brainsMDDProtein co-expression modulesProteomic profilingTruthful communication of mental science: pledge to our patients and profession
Malhi G, Marsh J, Ongur D, Cosci F, Krystal J, Cropsey K, Wegener G, Redline S, Pariante C, Hageman I, Carter C, Rief W, Emsley R, DeLisi L, Cipriani A, Crespo-Facorro B, Kisely S, Yatham L, Looi J, Mulder R, Tandon R, Dazzan P. Truthful communication of mental science: pledge to our patients and profession. The British Journal Of Psychiatry 2025, 226: 253-255. PMID: 40268759, DOI: 10.1192/bjp.2025.94.Peer-Reviewed Original ResearchAltmetricFunctional Validation of Alcohol Dependence-Associated FYN Variants Using Gene Editing and Stem Cell Study Approaches.
Cakir B, Tanaka Y, Choe M, Chu P, Xiang Y, Kim K, Zhong M, Gelernter J, Zhang H, Krystal J, Park I. Functional Validation of Alcohol Dependence-Associated FYN Variants Using Gene Editing and Stem Cell Study Approaches. International Journal Of Stem Cells 2025 PMID: 40205763, DOI: 10.15283/ijsc24123.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cell linesAlcohol dependenceAD-associated variantsEmbryonic stem cell linesReporter gene analysisFyn tyrosine kinase geneTyrosine kinase geneStem cell linesCRISPR-Cas9 editingAssociated with ADVulnerability to ADAD-associatedKinase geneC alleleC/T allelesMultiple polymorphismsFunctional validationGene analysisEthanol treatmentNeuropsychiatric disordersInduced neuronsAD treatmentGene editingCell linesDisease mechanisms
Clinical Trials
Current Trials
Have you had COVID-19?
HIC ID2000033404RoleSub InvestigatorPrimary Completion Date08/31/2025Recruiting ParticipantsStudying the Adult Brain
HIC ID2000025671RoleSub InvestigatorPrimary Completion Date07/31/2025Recruiting ParticipantsAMPA Receptor Components of the Anti-Depressant Ketamine Response
HIC ID2000021345RolePrincipal InvestigatorPrimary Completion Date06/30/2032Recruiting ParticipantsGenderBothAge18 years - 65 yearsEfficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study.
HIC ID2000020355RoleSub InvestigatorPrimary Completion Date07/31/2023Recruiting ParticipantsGenderBothAge21 years - 55 yearsImaging mGluR5 and synaptic density in psychiatric disorders
HIC ID2000020186RoleSub InvestigatorPrimary Completion Date01/31/2018Recruiting ParticipantsGenderBothAge18 years - 80 years
Academic Achievements & Community Involvement
Activities
activity NIMH
2016 - PresentPeer Review Groups and Grant Study SectionsMemberDetailsNIMH National Mental Health Advisory Councilactivity Neuroscience Forum, National Academies of Sciences, Engineering, and Medicine
07/01/2018 - PresentProfessional OrganizationsCo-DirectorDetailsCo-Directoractivity International College of Neuropsychopharmacology
07/01/2016 - 07/01/2018Professional OrganizationsPresidentDetailsPresidentactivity Studies of the impact of sexual trauma
01/02/2011 - 10/31/2016ResearchDetailsBergen, Hordaland, NorwayAbstract/SynopsisI am collaborating with Iris Steine, a Ph.D. candidate at the University of Bergen, as well has her mentors and colleagues, on studies on the clinical features and neurobiology of sexual trauma and its complications, including PTSD
activity Ketamine Psychosis
01/01/2010 - 01/01/2014ResearchDetailsGuangzhou, Guangdong Province, ChinaAbstract/SynopsisStudying the phenomenology and genetics of ketamine psychosis in relation to schizophrenia
Honors
honor Barbara Fish Memorial Award for Contributions to Basic, Translational, and Clinical Neuroscience
12/08/2024International AwardAmerican College of NeuropsychopharmacologyDetailsUnited Stateshonor Rhoda and Bernard Sarnat in International Mental Health Award
09/28/2023International AwardNational Academy of Medicine (USA)DetailsUnited Stateshonor Nasrallah Family Award for Psychiatric Neuroscience
05/21/2023National AwardAmerican Psychiatric AssociationDetailsUnited Stateshonor Sir John Gaddam Memorial Lecture and Medal
12/06/2022International AwardBritish Pharmacologic SocietyDetailsUnited Kingdomhonor Colvin Prize for Outstanding Achievement in Mood Disorders Research
11/01/2019International AwardBrain and Behavior Research FoundationDetailsUnited States
Clinical Care
Overview
John Krystal, MD, is a leading expert in the areas of alcoholism, post-traumatic stress disorder, schizophrenia, and depression. His work links psychopharmacology, neuroimaging, molecular genetics, and computational neuroscience to study the neurobiology and treatment of these disorders. He is best known for leading the discovery of the rapid antidepressant effects of ketamine in depressed patients.
He is a member of the U.S. National Academy of Medicine. He also serves in a variety of advisory and review capacities for NIAAA, NIMH, Wellcome Trust, Brain and Behavior Research Foundation, the Broad Institute, and the Karolinska Institutet.
Dr. Krystal previously served on the National Alcohol Abuse and Alcoholism Advisory Council (NIAAA), the Department of Defense Psychological Health Advisory Committee, and the NIMH Board of Scientific Counselors (chair, 2005-2007). He has led the American College of Neuropsychopharmacology (president, 2012), and International College of Neuropsychophamacology (president, 2016-2018).
Currently, he is co-chair of the Neuroscience Forum (NeuroForum) of the National Academies of Sciences, Engineering, and Medicine, a member of the NIMH National Mental Health Advisory Council, and he edits the journal, Biological Psychiatry (impact factor: 11.982).
Clinical Specialties
Fact Sheets
Depression
Learn More on Yale Medicine
Board Certifications
Psychiatry
- Certification Organization
- AB of Psychiatry & Neurology
- Original Certification Date
- 1991
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News
- July 14, 2025
Department of Psychiatry Honors Residents, Fellows, Faculty, Staff at 2025 Annual Commencement Ceremonies
- July 07, 2025Source: The Washington Post
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- June 30, 2025
On the Record
- April 24, 2025
New Clinical Trial Aims to Treat Depression in People with Parkinson’s Disease