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
- 966 Publications
- 88,028 Citations
- 250 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
- 966 Publications
- 88,028 Citations
- 250 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
- 966 Publications
- 88,028 Citations
- 250 Yale Co-Authors
Administrative Support
About
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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 the International College of Neuropsychopharmacology (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 New Haven Health System
- 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
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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
Ismene Petrakis, MD
Ilan Harpaz-Rotem, PhD, ABPP
Chadi Abdallah, MD
Schizophrenia
Stress Disorders, Post-Traumatic
Alcoholism
Veterans
Psychiatry
Neuroimaging
Publications
2026
Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode
Shim S, Jeong H, Bommersbach T, Nierenberg A, Zarate C, Kaster T, Correll C, McIntyre R, Krystal J, Rhee T. Ketamine Infusions and Rapid Reduction of Suicidal and Depressive Symptoms in Major Depressive Episode. JAMA Psychiatry 2026, 83 PMID: 42090166, PMCID: PMC13150733, DOI: 10.1001/jamapsychiatry.2026.0612.Peer-Reviewed Original ResearchAltmetricConceptsDepressive symptomsKetamine infusionRandomized clinical trialsSuicidal symptomsDepressive episodeIntravenous ketamineMajor depressive episodeRemission rateRates of depressive symptomsReduction of suicideAdverse eventsIntravenous ketamine infusionUS Food and Drug AdministrationHedges g standardized mean differencesSerious adverse eventsOff-label indicationsFood and Drug AdministrationMultiple subgroup analysesRandom-effects modelSuicideMDELonger-term outcomesEfficacy outcomesControl patientsKetamine35. Opposing Effects of Ketamine and Thiopental on Aperiodic EEG Activity: Implications for the Spectral Exponent as a Noninvasive Index of Cortical E/I Balance
Cortes-Briones J, Urrutia-Gandolfo J, Estevez P, Sengupta A, Basilico M, Skosnik P, D'Souza D, Limoncelli I, Krystal J. 35. Opposing Effects of Ketamine and Thiopental on Aperiodic EEG Activity: Implications for the Spectral Exponent as a Noninvasive Index of Cortical E/I Balance. Biological Psychiatry 2026, 99: s90. DOI: 10.1016/j.biopsych.2026.03.215.Peer-Reviewed Original ResearchAdditional analyses do not implicate opioid signaling in the antidepressant effects of ketamine
Yoon G, Pittman B, Krystal J. Additional analyses do not implicate opioid signaling in the antidepressant effects of ketamine. The International Journal Of Neuropsychopharmacology 2026, 29: pyag011. PMID: 41818343, PMCID: PMC13064640, DOI: 10.1093/ijnp/pyag011.Peer-Reviewed Original ResearchChildhood Maltreatment and Deviations from Normative Brain Structure: A Mega-Analysis of 3,711 Individuals from the ENIGMA MDD and ENIGMA PTSD Working Groups
Wang H, Liu Z, Pozzi E, Hussain A, Sigar P, Abdallah C, Alexander N, Baker J, Bauer J, Blackford J, Cisler J, Connolly C, Cotton A, Daniels J, Dannlowski U, Densmore M, deRoon-Cassini T, Dima D, Du Plessis S, Etkin A, Fani N, Fisch L, Fitzgerald J, Frodl T, Fu C, Gonul A, Gordon E, Gotlib I, Goya-Maldonado R, Groenewold N, Grotegerd D, Hahn T, Hamilton J, Han L, Harpaz-Rotem I, Haswell C, Herringa R, Herzog J, Ipser J, Jahanshad N, Jovanovic T, Kaufman M, Kircher T, Konowski M, Koopowitz S, Krug A, Krystal J, Lanius R, Larson C, Lazarov A, Lebois L, Leehr E, Levy I, Li M, Manthey A, Maron-Katz A, McIntosh A, McLaughlin K, Meinert S, Mwangi B, Nelson S, Nenadić I, Neria Y, Neufeld R, Ojha A, Olatunji B, Olson E, Opel N, Peverill M, Ressler K, Ross M, Rosso I, Sacchet M, Sambrook K, Schmahl C, Seedat S, Shenton M, Sicorello M, Sierk A, Soares J, Stein D, Stein F, Stein M, Suarez-Jimenez B, Théberge J, Thomopoulos S, Tomas C, Usemann P, van den Heuvel L, van Rooij S, Walter H, Walter M, Wang X, Whalley H, Winter N, Wu M, Xie H, Yang T, Zhu X, Zilcha-Mano S, Zunta-Soares G, Frangou S, Thompson P, Salminen L, Sun D, Morey R, Stevens J, Schmaal L, Ho T. Childhood Maltreatment and Deviations from Normative Brain Structure: A Mega-Analysis of 3,711 Individuals from the ENIGMA MDD and ENIGMA PTSD Working Groups. Biological Psychiatry 2026 PMID: 41791639, DOI: 10.1016/j.biopsych.2026.02.016.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMajor depressive disorderPosttraumatic stress disorderChildhood maltreatmentSubcortical volumesCortical thicknessWhole-brain MRI dataMedial orbitofrontal cortexMiddle frontal regionsAssociated with large volumesOrbitofrontal cortexDepressive disorderTransdiagnostic effectsStress disorderNeuroanatomical alterationsBrain morphometryPutamen volumeIsthmus cingulateParietal regionsBrain structuresFrontal regionsOccipital cortexMega-AnalysisEntorhinal cortexAdverse experiencesAssociated with elevated riskSocial Determinants of Health and Suicide Risk in US Military Veterans
Pietrzak R, Fischer I, Nichter B, Esterlis I, Krystal J, Moutier C, Oquendo M, Jeste D, Na P. Social Determinants of Health and Suicide Risk in US Military Veterans. JAMA Psychiatry 2026, 83: 315-318. PMID: 41432940, PMCID: PMC12728726, DOI: 10.1001/jamapsychiatry.2025.3883.Peer-Reviewed Original ResearchCitationsAltmetricModulating the endocannabinoid system in alcohol use disorder: A translational systematic review and meta-analysis of preclinical and human studies
Costa G, Cerezo-Matias M, Funaro M, Bagdas D, Kaye A, Krystal J, Petrakis I, De Aquino J. Modulating the endocannabinoid system in alcohol use disorder: A translational systematic review and meta-analysis of preclinical and human studies. Molecular Psychiatry 2026, 1-23. PMID: 41760917, DOI: 10.1038/s41380-026-03523-5.Peer-Reviewed Original ResearchThis study investigates targeting the endocannabinoid system for alcohol use disorder, finding promising preclinical results for cannabidiol and CB1 receptor modulators, but inconsistent human trial outcomes highlight the need for better-designed clinical studies.Central amygdala single-nucleus atlas reveals chromatin and gene transcription dynamics in human alcohol use disorder
Lee C, Hwang A, McRiley D, Lee J, Thibodeau G, Duman C, Zhang X, Skarica M, Coudriet J, Xu S, Terwilliger R, Sliby A, Wang J, Nguyen T, Liu Y, Li H, Dai Y, Duan Z, Lei Y, Lin Y, Glausier J, Lewis D, Gelernter J, Holtzheimer P, Xu K, Zhou H, Zhao H, Thompson S, Krystal J, Che A, Taylor J, Zhang J, Girgenti M. Central amygdala single-nucleus atlas reveals chromatin and gene transcription dynamics in human alcohol use disorder. Nature Communications 2026, 17: 1634. PMID: 41554730, PMCID: PMC12905162, DOI: 10.1038/s41467-026-68351-1.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAlcohol use disorderCandidate cis-regulatory elementsCell type-specific gene expressionGene expressionFunctional genomic elementsRegulation of gene expressionTranscription factor footprintsCis-regulatory elementsGene transcription dynamicsCell typesCell type-specificHuman alcohol use disordersUse disorderGenomic elementsChromatin loopsGWAS genesChromatin accessibilityTranscriptional dynamicsExpressed genesRisk genesCNS cell typesGenesCentral amygdalaType-specificInhibitory neurons
2025
Combining DNA methylation features and clinical characteristics predicts ketamine treatment response for PTSD
Valizadeh A, Roache J, Zhang X, Hu Y, Gueorguieva R, Averill L, Ranganathan M, Wang Z, Williamson D, Shiroma P, Girgenti M, Petrakis I, López-Roca A, Young-McCaughan S, Keane T, Peterson A, Abdallah C, Krystal J, Xu K, PTSD F. Combining DNA methylation features and clinical characteristics predicts ketamine treatment response for PTSD. IScience 2025, 29: 114445. PMID: 41561376, PMCID: PMC12814687, DOI: 10.1016/j.isci.2025.114445.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPost-traumatic stress disorderDNA methylation patternsDNA methylation featuresDNA methylation profilesStudies of ketamineBlood DNA methylation profilesBenefits of ketamineTreatment responseNear genesRisk lociMethylation sitesMethylation patternsMethylation featuresStress disorderMethylation profilesGlutamatergic signalingResponse subgroupsKetamineClinical measuresClinical variablesRandomized studyImmune regulationBiological variablesLociCpGsA translational neuroscience & computational evaluation of a D1R partial agonist for schizophrenia (TRANSCENDS): Rationale and study design of a brain-based clinical trial
Fonteneau C, Tamayo Z, Price A, Pan L, Afriyie-Agyemang Y, Agrawal S, Butler A, Cail C, Calkins M, Chakilam A, Forselius-Bielen K, Fram G, Frazier A, Gil R, Govil P, Gray D, Grinband J, Gur R, Haubold N, Heffernan Z, Heneks M, Kegeles L, Kohler C, Lin C, Lu J, Mayer M, Pham P, Perlman G, Rahmati M, Ranganathan M, Santamauro N, Schutte C, Selloni A, Van Snellenberg J, Surti T, Wolf D, Zharyy C, Group T, Abi-Dargham A, Gur R, Lieberman J, Kantrowitz J, Anticevic A, Cho Y, Krystal J. A translational neuroscience & computational evaluation of a D1R partial agonist for schizophrenia (TRANSCENDS): Rationale and study design of a brain-based clinical trial. Journal Of Psychiatric Research 2025, 194: 196-210. PMID: 41519104, PMCID: PMC13138834, DOI: 10.1016/j.jpsychires.2025.12.020.Peer-Reviewed Original ResearchConceptsPartial agonistCognitive impairmentSpatial working memoryDouble-blind doseWorking memoryD1/D5 receptorsFunctional neuroimagingNeural mechanismsSchizophreniaTranslational neuroscienceCognitive paradigmNeural circuitsUntreated symptomsD1RDecades of researchFMRIClinical trialsMicro-circuitryNeuroscienceAgonistsImpairmentStudy designD1/D5Clinical dataNeuroimagingEfficacy and safety of iclepertin for cognitive impairment associated with schizophrenia (CONNEX programme): results from three phase 3 randomised controlled trials
Keefe R, Harvey P, Correll C, Falkai P, Hashimoto N, Klein H, Krystal J, Marder S, Medalia A, Sumiyoshi T, Wang G, Zhang H, Blahova Z, Bichard-Sall I, English B, Fu E, Gruenenfelder F, Groeschl M, Kimura K, Tang W, von der Goltz C, Fowler C. Efficacy and safety of iclepertin for cognitive impairment associated with schizophrenia (CONNEX programme): results from three phase 3 randomised controlled trials. The Lancet Psychiatry 2025, 12: 906-920. PMID: 41233083, DOI: 10.1016/s2215-0366(25)00296-2.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsComposite T-scoreDose of trial medicationCognitive impairment associated with schizophreniaConsensus Cognitive BatteryGlycine transporter-1Trial medicationAntipsychotic therapyCognitive batteryT-scoreTreatment researchPsychiatric centreSchizophreniaPlacebo-controlled trialPrimary endpointSelection of outcome measuresAssociated with significant improvementsCognitive impairmentTreatment of CIAOn-treatment adverse eventsPhase 3 randomised controlled trialDouble-blindInteractive response technologyCognitionMCCBTolerability assessments
Clinical Trials
Current Trials
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IRB ID2000033404RoleSub InvestigatorPrimary Completion Date08/31/2025Recruiting ParticipantsStudying the Adult Brain
IRB ID2000025671RoleSub InvestigatorPrimary Completion Date07/31/2025Recruiting ParticipantsAMPA Receptor Components of the Anti-Depressant Ketamine Response
IRB ID2000021345RolePrincipal InvestigatorPrimary Completion Date06/30/2032Recruiting ParticipantsGenderBothAge18 years - 65 yearsEfficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study.
IRB ID2000020355RoleSub InvestigatorPrimary Completion Date07/31/2023Recruiting ParticipantsGenderBothAge21 years - 55 yearsImaging mGluR5 and synaptic density in psychiatric disorders
IRB ID2000020186RoleSub InvestigatorPrimary Completion Date01/31/2018Recruiting ParticipantsGenderBothAge18 years - 80 years
Academic Achievements & Community Involvement
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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
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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
- May 26, 2026Source: The Journal of Clinical Psychiatry
National Trends in Posttraumatic Stress Disorder Among US Military Veterans: Results From the 2025–2026 National Health and Resilience in Veterans Study
- May 20, 2026
Hyman Honored with 2026 Yale Department of Psychiatry Mental Health Advocacy Award
- May 18, 2026
Krystal Awarded 2026 Connecticut Medal of Technology
- May 08, 2026Source: Journal-Gazette (with John Krystal, MD)
What to Know About Psychedelic Retreats, a Booming Business with Few Safety Guardrails
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