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
- 948 Publications
- 83,834 Citations
- 232 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
- 948 Publications
- 83,834 Citations
- 232 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
- 948 Publications
- 83,834 Citations
- 232 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
- 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
A remote care navigation solution associated with improved utilization and outcomes of mental healthcare: A nationwide cohort study in the USA
Ward E, Hawrilenko M, Ambwani G, Brown M, Krystal J, Corlett P, Chekroud A. A remote care navigation solution associated with improved utilization and outcomes of mental healthcare: A nationwide cohort study in the USA. PLOS ONE 2025, 20: e0331454. PMID: 40966254, PMCID: PMC12445557, DOI: 10.1371/journal.pone.0331454.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsCare navigationMental healthcare utilizationHealthcare utilizationCohort studyComplete demographic informationMental health benefitsMental health assessmentNationwide cohort studyAssociated with greater engagementMental healthcareCare utilizationRetrospective cohort studyPeople of colorScheduling appointmentsWhite participantsHealth assessmentCareGreater engagementParticipants of colorDemographic informationClinical implementationBaseline symptomsHealth benefitsParticipantsUS employersDevelopmental timing of index trauma exposure and accelerated epigenetic aging in United States military veterans
Tamman A, Nagamatsu S, Cabrera-Mendoza B, Averill L, Dunn E, Krystal J, Gelernter J, Montalvo-Ortiz J, Polimanti R, Pietrzak R. Developmental timing of index trauma exposure and accelerated epigenetic aging in United States military veterans. Psychoneuroendocrinology 2025, 182: 107568. PMID: 41016323, DOI: 10.1016/j.psyneuen.2025.107568.Peer-Reviewed Original ResearchConceptsUnited States military veteransTrauma typesTrauma exposureMilitary veteransNational Health and ResilienceExposure to interpersonal violenceInterpersonal violenceNon-interpersonal traumaVeterans StudySelf-reported ageTrauma characteristicsEpigenetic ageTrauma burdenVeteransChronological ageGrimAgeViolenceGreater oddsDevelopmental timeTraumaYounger ageRecencyLong-term health risksPotential confoundersAgeKetamine for Depression, but at What Cost? A Review of Ketamine’s Neurotoxic Effects From Preclinical and Human Studies
Li S, Kumpf K, Urrutia J, Krystal J, Sanacora G, Wilkinson S. Ketamine for Depression, but at What Cost? A Review of Ketamine’s Neurotoxic Effects From Preclinical and Human Studies. American Journal Of Psychiatry 2025, 182: 903-912. PMID: 40926573, DOI: 10.1176/appi.ajp.20250276.Peer-Reviewed Original ResearchCitationsAltmetricConceptsCognitive functionExecutive function impairmentNeurotoxic effectsLower cognitive functionHuman clinical trialsIntranasal esketamineClinical trialsCognitive deficitsSubanesthetic dosesKetamine administrationKetamine usersCognitive AssessmentRobust longitudinal researchEsketamineLongitudinal researchRacemic ketamineNonhuman primate modelRecreational usersObservational studyExcitotoxic neuronal damageFunctional impairmentKetamineDirect comparisonIntegrated findingsPreclinical researchAntidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial
Yoon G, Pittman B, Ralevski E, Petrakis I, Krystal J. Antidepressant efficacy of ketamine plus naltrexone for major depression comorbid with alcohol use disorder: a randomized controlled trial. The International Journal Of Neuropsychopharmacology 2025, 28: pyaf056. PMID: 40795937, PMCID: PMC12395335, DOI: 10.1093/ijnp/pyaf056.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMajor depressive disorderAlcohol use disorderKetamine's therapeutic effectsAntidepressant effectsEfficacy of ketamineAntidepressant efficacyUse disorderGroup differencesComorbidity of major depressive disorderMontgomery-Asberg Depression Rating ScaleTreatment of Major Depressive DisorderAntidepressant efficacy of ketamineComorbid major depressive disorderAntidepressant effects of ketamineNMDA glutamate receptor antagonistDepression Rating ScaleAnti-alcohol effectsAlcohol-related outcomesNo group differencesOpioid receptor antagonismEffects of ketamineKetamine groupAlcohol cravingMADRS changeMontgomery-AsbergA whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study
See C, Si S, Baird C, Haswell C, Hussain A, Olff M, Veltman D, Frijling J, van Zuiden M, Koch S, Nawijn L, Wang L, Zhu Y, Li G, Neria Y, Zhu X, Suarez-Jimenez B, Zilcha-Mano S, Lazarov A, Stevens J, Ressler K, Fani N, Jovanovic T, van Rooij S, Kaufman M, Lebois L, Rosso I, Olson E, Baker J, Sponheim S, Disner S, Davenport N, Etkin A, Maron-Katz A, Stein M, Shenton M, Stein D, Ipser J, Koopowitz S, Seedat S, du Plessis S, van den Heuvel L, Lissek S, Berg H, Straube T, Hofman D, Baugh L, Forster G, Simons R, Simons J, Magnotta V, Fercho K, Wang X, Cotton A, O'Leary E, Xie H, Grupe D, Nitschke J, Davidson R, Larson C, deRoon-Cassini T, Tomas C, Fitzgerald J, Blackford J, Olatunji B, Gordon E, May G, Nelson S, Lanius R, Théberge J, Densmore M, Neufeld R, Abdallah C, Averill C, Harpaz-Rotem I, Levy I, Krystal J, Geuze E, van Lutterveld R, Dennis E, Tate D, Cifu D, Walker W, Wilde E, van der Wee N, Vermeiren R, van der Werff S, McLaughlin K, Sambrook K, Peverill M, Radua J, Salminen L, Jahanshad N, Thomopoulos S, James A, Valmaggia L, Thompson P, Morey R, Kempton M. A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study. European Psychiatry 2025, 68: e97. PMID: 40692500, PMCID: PMC12344465, DOI: 10.1192/j.eurpsy.2025.10062.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPosttraumatic stress disorder patientsPosttraumatic stress disorderAssociated with GM volumeWhole-brain voxel-based analysisVoxel-based morphometryRegional brain volumesGM volumeBrain volumeDepression severityWhole-brainPosttraumatic stress disorder severityWhole-brain statistical mapsCerebellar WM volumeTrauma-exposed controlsStructural neuroimaging scansSuperior frontal gyrusGray matterStatistical mapsVoxel-wise differencesAnalysis of structural abnormalitiesFrontal gyrusTrauma exposureMemory processesStress disorderWhite matterInteractions of alcohol and the benzodiazepine inverse agonist in healthy male volunteers
Singh N, Petrakis I, Pittman B, Luddy C, Krystal J, DSouza D. Interactions of alcohol and the benzodiazepine inverse agonist in healthy male volunteers. Journal Of Psychopharmacology 2025, 39: 715-725. PMID: 40673436, DOI: 10.1177/02698811251330746.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsBenzodiazepine partial inverse agonistPartial inverse agonistGABA-A receptorsEthanol intoxicationInverse agonistsGABA-ASedative effectsSedative effects of alcoholAlcohol intoxicationEffects of alcohol intoxicationBenzodiazepine inverse agonistGABA-A receptor subtypesHealthy male volunteersExtrasynaptic GABA-A receptorsWithin-subject designEffects of alcoholStandard alcoholic drinksInteraction of alcoholAffect ScaleAlcohol effectsGABAergic modulationMale volunteersIntravenous alcoholBenzodiazepinesAlcohol drinkingThe impact of chronic pain on brain gene expression.
Collier L, Seah C, Hicks E, Holtzheimer P, Krystal J, Girgenti M, Huckins L, Johnston K. The impact of chronic pain on brain gene expression. Pain 2025 PMID: 40623285, PMCID: PMC12236435, DOI: 10.1097/j.pain.0000000000003707.Peer-Reviewed Original ResearchAltmetricConceptsChronic pain developmentChronic painPain developmentMechanisms of chronic pain developmentEffects of chronic painImpact of chronic painCell typesBrain gene expressionPain-related factorsGene expressionDifferential gene expressionBrain regionsSignificant public health burdenPublic health burdenImmune response pathwaysPain genesAmygdala cellsBasolateral amygdalaBrain regional levelsPainInvestigate sex differencesMigraineAssociated treatmentHealth burdenPostmortem donorsA common symptom geometry of mood improvement under sertraline and placebo associated with distinct neural patterns
Berkovitch L, Lee K, Ji J, Helmer M, Rahmati M, Demsar J, Kraljic A, Matkovic A, Tamayo Z, Murray J, Repovs G, Krystal J, Martin W, Fonteneau C, Anticevic A. A common symptom geometry of mood improvement under sertraline and placebo associated with distinct neural patterns. Psychological Medicine 2025, 55: e185. PMID: 40611472, PMCID: PMC12270277, DOI: 10.1017/s0033291725100962.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsMechanisms of Major depressive disordersGlobal brain connectivitySymptom improvementClinical Global Impression ScaleGlobal Impression ScaleMajor depressive disorderManic-like symptomsMeasures of clinical improvementAntidepressant treatmentImpression ScaleDepressive disorderNeural profilesMood improvementSuicidal ideasPattern of clinical improvementSymptom ScaleClinical scalesNeural patternsSertralineBrain connectivityNeural circuitsIndividual itemsPatients' scoresClinical improvementImproved scoresBiological Psychiatry: A Brief Note of Thanks
Krystal J. Biological Psychiatry: A Brief Note of Thanks. Biological Psychiatry 2025, 98: 366-367. PMID: 40614796, DOI: 10.1016/j.biopsych.2025.06.019.Peer-Reviewed Original ResearchAltmetricSingle-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, 643: 744-754. PMID: 40533550, PMCID: PMC12267058, 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 disorder
Clinical Trials
Current Trials
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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
- November 12, 2025
Twenty-Seven YSM Faculty Members Recognized for Highly Cited Research
- October 09, 2025Source: CBS Village
Could ketamine help first responders with depression, PTSD? The largely unregulated treatment faces hurdles.
- September 30, 2025Source: Everyday Health
What Is Treatment-Resistant Depression?
- September 18, 2025
Yale Scientists Seek to Uncover Neural and Genomic Mechanisms that Drive Anxiety