2024
Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression
Swanberg K, Prinsen H, Averill C, Campos L, Kurada A, Krystal J, Petrakis I, Averill L, Rothman D, Abdallah C, Juchem C. Medial prefrontal cortex neurotransmitter abnormalities in posttraumatic stress disorder with and without comorbidity to major depression. NMR In Biomedicine 2024, 37: e5220. PMID: 39054694, DOI: 10.1002/nbm.5220.Peer-Reviewed Original ResearchPosttraumatic stress disorderMedial prefrontal cortexStress disorderPosttraumatic stress disorder patientsPosttraumatic stress disorder diagnosisChronic psychiatric conditionImpact of psychiatric comorbiditiesComorbid MDDPrefrontal cortexDepressive disorderTraumatic stressorsPsychiatric conditionsMDDPsychiatric comorbiditiesNeurotransmitter abnormalitiesConcentrations of glutamateMetabolite abnormalitiesHealthy controlsDisordersPattern of abnormalitiesParticipantsGlutamateIn vivo protonMetabolic abnormalitiesDepression
2023
Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods
Yang J, Huggins A, Sun D, Baird C, Haswell C, Frijling J, Olff M, van Zuiden M, Koch S, Nawijn L, Veltman D, Suarez-Jimenez B, Zhu X, Neria Y, Hudson A, Mueller S, Baker J, Lebois L, Kaufman M, Qi R, Lu G, Říha P, Rektor I, Dennis E, Ching C, Thomopoulos S, Salminen L, Jahanshad N, Thompson P, Stein D, Koopowitz S, Ipser J, Seedat S, du Plessis S, van den Heuvel L, Wang L, Zhu Y, Li G, Sierk A, Manthey A, Walter H, Daniels J, Schmahl C, Herzog J, Liberzon I, King A, Angstadt M, Davenport N, Sponheim S, Disner S, Straube T, Hofmann D, Grupe D, Nitschke J, Davidson R, Larson C, deRoon-Cassini T, Blackford J, Olatunji B, Gordon E, May G, Nelson S, Abdallah C, Levy I, Harpaz-Rotem I, Krystal J, Morey R, Sotiras A. Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods. Neuropsychopharmacology 2023, 49: 609-619. PMID: 38017161, PMCID: PMC10789873, DOI: 10.1038/s41386-023-01763-5.Peer-Reviewed Original ResearchPosttraumatic stress disorderStructural covariance networksCortical thicknessPTSD diagnosisInsular cortexPTSD patientsCingulate cortexSymptom severityBilateral superior frontal cortexStress disorderGreater cortical thicknessLower cortical thicknessChildhood trauma severitySuperior frontal cortexRegression analysisAnterior cingulate cortexTrauma-exposed controlsPosterior cingulate cortexPrefrontal regulatory regionsPTSD symptom severityComorbid depressionMotor cortexHealthy controlsFrontal cortexAlcohol abuse
2022
Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder
Smart K, Worhunsky PD, Scheinost D, Angarita GA, Esterlis I, Carson RE, Krystal JH, O'Malley SS, Cosgrove KP, Hillmer AT. Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder. Alcohol Clinical And Experimental Research 2022, 46: 770-782. PMID: 35342968, PMCID: PMC9117461, DOI: 10.1111/acer.14816.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsDefault mode networkFunctional magnetic resonance imagingReceptor availabilityPositron emission tomographyAUD groupFunctional connectivityReceptor positron emission tomographyResting-state functional magnetic resonance imagingNetwork-level functional connectivityBrain connectivityWeeks of abstinenceGlobal functional connectivityAlcohol use disorderMagnetic resonance imagingFMRI outcomesHealthy controlsSupervised abstinencePET resultsUse disordersSynaptic plasticityResonance imagingBrain regionsEmission tomographyOrbitofrontal cortexValidation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia
Abram SV, Roach BJ, Fryer SL, Calhoun VD, Preda A, van Erp TGM, Bustillo JR, Lim KO, Loewy RL, Stuart BK, Krystal JH, Ford JM, Mathalon DH. Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia. Molecular Psychiatry 2022, 27: 2448-2456. PMID: 35422467, PMCID: PMC9135621, DOI: 10.1038/s41380-022-01502-0.Peer-Reviewed Original ResearchConceptsThalamic dysconnectivityHealthy controlsDysconnectivity patternsIllness courseHealthy volunteersN-methyl-D-aspartate (NMDA) receptor hypofunctionResting-state functional magnetic resonance imaging studyHallucination severityEarly illness schizophreniaExcess glutamate releaseGlutamate release inhibitorNMDAR antagonist ketaminePlacebo-controlled studyMagnetic resonance imaging studySub-anesthetic dosesSchizophrenia-like symptomsResonance imaging studyFunctional magnetic resonance imaging studyKetamine infusionGlutamate releaseNMDAR hypofunctionReceptor hypofunctionKetamine effectsThalamic connectivityRelease inhibitorImaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptomsPrefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans
Averill LA, Jiang L, Purohit P, Coppoli A, Averill CL, Roscoe J, Kelmendi B, De Feyter HM, de Graaf RA, Gueorguieva R, Sanacora G, Krystal JH, Rothman DL, Mason GF, Abdallah CG. Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans. Chronic Stress 2022, 6: 24705470221092734. PMID: 35434443, PMCID: PMC9008809, DOI: 10.1177/24705470221092734.Peer-Reviewed Original ResearchGlutamatergic synaptic strengthSynaptic strengthPathophysiology of PTSDNovel putative biomarkersTrauma-related psychopathologyMagnetic resonance spectroscopyGlutamate neurotransmissionHealthy controlsNew treatmentsChronic stressPatientsPutative biomarkersEffects of sexPTSDNeurotransmissionPosttraumatic stressAgePsychopathologyEPCPathophysiologyStudy resultsTraumaBiomarkers
2020
Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia
Hamilton HK, Roach BJ, Cavus I, Teyler TJ, Clapp WC, Ford JM, Tarakci E, Krystal JH, Mathalon DH. Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia. Frontiers In Psychiatry 2020, 11: 590567. PMID: 33391054, PMCID: PMC7772351, DOI: 10.3389/fpsyt.2020.590567.Peer-Reviewed Original ResearchLong-term potentiationN-methyl-D-aspartate receptorsHealthy controlsNeuroplastic changesPlasticity paradigmsHigh-frequency electrical stimulationExperience-dependent synaptic plasticityVisual cortical plasticityPathophysiology of schizophreniaHigh-frequency stimulationNMDA receptor dysfunctionFrequency electrical stimulationTheta oscillationsVisual stimuliImpaired potentiationGlutamatergic transmissionReceptor dysfunctionImpaired neuroplasticityEvent-related EEG oscillationsNMDAR hypofunctionCortical plasticityVEP amplitudeAnimal modelsElectrical stimulationWhite checkerboard stimuliLongitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence
Hillmer AT, Angarita GA, Esterlis I, Anderson JM, Nabulsi N, Lim K, Ropchan J, Carson RE, Krystal JH, Malley S, Cosgrove KP. Longitudinal imaging of metabotropic glutamate 5 receptors during early and extended alcohol abstinence. Neuropsychopharmacology 2020, 46: 380-385. PMID: 32919411, PMCID: PMC7852514, DOI: 10.1038/s41386-020-00856-9.Peer-Reviewed Original ResearchConceptsMetabotropic glutamate 5 receptorsSmoking statusAlcohol abstinenceEarly abstinenceMGlu5 receptor negative allosteric modulatorReceptor negative allosteric modulatorChronic alcohol useCortical brain regionsAlcohol use disorderEmission Tomography ImagingPositron emission tomography (PET) imagingNegative allosteric modulatorsDSM-5 criteriaCue-induced reinstatementHealthy controlsPreclinical literatureGlutamate systemPreclinical modelsHuman evidenceReceptor drugsPET scansUse disordersHuman studiesReceptor availabilityStudy duration
2019
Lower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2017
Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment
Abdallah CG, Averill CL, Salas R, Averill LA, Baldwin PR, Krystal JH, Mathew SJ, Mathalon DH. Prefrontal Connectivity and Glutamate Transmission: Relevance to Depression Pathophysiology and Ketamine Treatment. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2017, 2: 566-574. PMID: 29034354, PMCID: PMC5635826, DOI: 10.1016/j.bpsc.2017.04.006.Peer-Reviewed Original ResearchTreatment-resistant depressionTRD patientsHealthy subjectsHealthy controlsStudy AStudy BEffects of lamotrigineAbility of ketamineGlobal brain connectivityEffects of ketamineFunctional magnetic resonance imagingMagnetic resonance imagingSignificant reductionOral lamotrigineKetamine treatmentKetamine infusionKetamine's mechanismGlutamate transmissionGlutamate neurotransmissionDepression pathophysiologyPharmacological challengeKetamine interactionKetaminePrefrontal connectivityResonance imagingKetamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression
Esterlis I, DellaGioia N, Pietrzak RH, Matuskey D, Nabulsi N, Abdallah CG, Yang J, Pittenger C, Sanacora G, Krystal JH, Parsey RV, Carson RE, DeLorenzo C. Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression. Molecular Psychiatry 2017, 23: 824-832. PMID: 28397841, PMCID: PMC5636649, DOI: 10.1038/mp.2017.58.Peer-Reviewed Original ResearchConceptsMajor depressive disorderMGluR5 availabilityPositron emission tomographyKetamine administrationControl groupAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced reductionMetabotropic glutamatergic receptorsRapid antidepressant effectsGlutamate receptor antagonistsKetamine-induced changesEffects of ketaminePET imaging studiesMechanism of actionGlutamate surgeAntidepressant effectsAntidepressant efficacyAntidepressant responseGlutamatergic receptorsControl subjectsReceptor antagonistHealthy controlsDepressive disorderSustained decrease
2012
A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference
Anticevic A, Repovs G, Krystal JH, Barch DM. A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference. Schizophrenia Research 2012, 141: 8-14. PMID: 22863548, PMCID: PMC3879404, DOI: 10.1016/j.schres.2012.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceBrain MappingFemaleFunctional LateralityHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory DisordersMemory, Short-TermMiddle AgedNerve NetNeural PathwaysNeuropsychological TestsOxygenPrefrontal CortexSchizophreniaSchizophrenic PsychologyConceptsFunctional connectivity abnormalitiesConnectivity abnormalitiesMedio-dorsal thalamusTask-based functional connectivityFinal common pathwayMaintenance phasePrefrontal cortical regionsDorsolateral prefrontal cortex activationPrefrontal cortex activationFunctional deficitsHealthy controlsSub-cortical regionsExtended amygdalaPatientsCortex activationCognitive deficitsCortical regionsFunctional connectivityLife outcomesAbnormalitiesDLPFC networkCommon pathwaySchizophrenia researchSchizophreniaMemory abnormalities
2009
Population admixture modulates risk for alcohol dependence
Zuo L, Luo X, Listman JB, Kranzler HR, Wang S, Anton RF, Blumberg HP, Stein MB, Pearlson GD, Covault J, Charney DS, van Kammen DP, Price LH, Lappalainen J, Cramer J, Krystal JH, Gelernter J. Population admixture modulates risk for alcohol dependence. Human Genetics 2009, 125: 605-613. PMID: 19306106, PMCID: PMC2777998, DOI: 10.1007/s00439-009-0647-4.Peer-Reviewed Original Research
2008
The effects of cannabinoids on serum cortisol and prolactin in humans
Ranganathan M, Braley G, Pittman B, Cooper T, Perry E, Krystal J, D’Souza D. The effects of cannabinoids on serum cortisol and prolactin in humans. Psychopharmacology 2008, 203: 737. PMID: 19083209, PMCID: PMC2863108, DOI: 10.1007/s00213-008-1422-2.Peer-Reviewed Original ResearchConceptsPlasma prolactin levelsPlasma cortisol levelsProlactin levelsNeuroendocrine effectsCannabis exposureHealthy controlsNeuroendocrine functionHormonal levelsCortisol levelsFrequent usersChronic cannabis exposureHealthy control subjectsDose-related increaseEffects of cannabinoidsBaseline hormonal levelsDose-related effectsDevelopment of toleranceLimited dose-response dataDose-dependent mannerBlunted increaseMultiple dosesControl subjectsSerum cortisolHormone levelsPlasma cortisolβ 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder
Czermak C, Staley JK, Kasserman S, Bois F, Young T, Henry S, Tamagnan GD, Seibyl JP, Krystal JH, Neumeister A. β 2 Nicotinic acetylcholine receptor availability in post-traumatic stress disorder. The International Journal Of Neuropsychopharmacology 2008, 11: 419-424. PMID: 18190729, DOI: 10.1017/s1461145707008152.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderClinician-Administered PTSD ScaleMesiotemporal cortexPTSD patientsPathophysiology of PTSDStress disorderBeta2 nAChRsNicotinic acetylcholine receptor availabilityHistory of smokingHealthy control subjectsNicotinic acetylcholine receptorsIA bindingNovel molecular targetsSingle photon emissionSubgroup of participantsRe-experiencing symptom clusterIA-85380Symptomatic patientsControl subjectsHealthy controlsReceptor availabilityPTSD ScaleAcetylcholine receptorsSymptom clustersPrefrontal cortexBlunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis
D'Souza DC, Ranganathan M, Braley G, Gueorguieva R, Zimolo Z, Cooper T, Perry E, Krystal J. Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis. Neuropsychopharmacology 2008, 33: 2505-2516. PMID: 18185500, PMCID: PMC3799954, DOI: 10.1038/sj.npp.1301643.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmnesiaAttentionBrainDose-Response Relationship, DrugDouble-Blind MethodDronabinolDrug Administration ScheduleDrug ToleranceFemaleHallucinationsHallucinogensHumansHydrocortisoneMaleMarijuana AbuseMiddle AgedPerceptual DisordersProlactinPsychoses, Substance-InducedTachycardiaYoung AdultConceptsAmnestic effectsPerceptual alterationsDelta-9-TetrahydrocannabinolCannabis useSubjective effectsFrequent usersCannabisEffects of cannabinoidsIllicit substancesPsychotomimetic effectsEuphoric effectsHealthy controlsHealthy individualsMemoryImpairingPsychosisDose-related effectsIndividualsCortisolPsychotomimeticsAttentionPeopleUsersPlacebo-controlled studyEffectRelationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study
Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, Bressan RA, Krystal JH, Ell PJ, Pilowsky LS. Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy—a [123I]CNS-1261 SPET study. Psychopharmacology 2008, 197: 401-408. PMID: 18176855, DOI: 10.1007/s00213-007-1047-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrief Psychiatric Rating ScaleDose-Response Relationship, DrugGuanidinesHumansInfusions, IntravenousIodine RadioisotopesKetamineMalePrefrontal CortexPsychoses, Substance-InducedReceptors, N-Methyl-D-AspartateSchizophreniaSingle-Blind MethodTomography, Emission-Computed, Single-PhotonConceptsBrief Psychiatric Rating ScaleVolume of distributionNMDA receptorsPsychotic symptomsN-methyl-D-aspartate receptorsKetamine-induced psychotic symptomsSingle photon emission tomographyNMDA receptor bindingEffects of ketamineNegative subscaleHealthy human controlsPsychiatric Rating ScaleNegative psychotic symptomsInferior frontal cortexKetamine administrationBolus infusionHealthy controls
2006
Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study
Epperson CN, Gueorguieva R, Czarkowski KA, Stiklus S, Sellers E, Krystal JH, Rothman DL, Mason GF. Preliminary evidence of reduced occipital GABA concentrations in puerperal women: a 1H-MRS study. Psychopharmacology 2006, 186: 425. PMID: 16724188, DOI: 10.1007/s00213-006-0313-7.Peer-Reviewed Original ResearchConceptsPostpartum major depressionCortical GABA concentrationsGABA concentrationPostpartum womenOccipital cortex GABA concentrationsOccipital cortex GABA levelsProton magnetic resonance spectroscopy studyFollicular phase femalesGamma-aminobutyric acid concentrationResumption of menstruationFollicular phase womenMonths of deliveryMid-follicular phaseOvarian hormone levelsSubgroup of womenMagnetic resonance spectroscopy studyAllopregnanolone concentrationsPuerperal womenALLO levelsBlood levelsPostpartum periodHealthy controlsMajor depressionGABA levelsHormone levels
2004
Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-Specific Alterations of γ-Aminobutyric Acid and Glutamatein Patients With Major Depression. JAMA Psychiatry 2004, 61: 705-713. PMID: 15237082, DOI: 10.1001/archpsyc.61.7.705.Peer-Reviewed Original ResearchConceptsMajor depressive disorderGamma-aminobutyric acidOccipital cortex GABA concentrationsProton magnetic resonance spectroscopyDepressed subjectsGABA concentrationHealthy controlsSubtypes of MDDCortical gamma-aminobutyric acidHealthy control subjectsMetabolite levelsCholine-containing compoundsHealthy comparison subjectsClinical research programSubtype-specific alterationsΓ-aminobutyric acidClinical correlatesMDD patientsControl subjectsDepressive disorderNeurotransmitter levelsGlutamate levelsMajor depressionMDD subtypesOccipital cortex
1999
CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls
Petrakis I, Trevisan L, D'Souza C, Gil R, Krasnicki S, Webb E, Heninger G, Cooney N, Krystal J. CSF Monoamine Metabolite and Beta Endorphin Levels in Recently Detoxified Alcoholics and Healthy Controls. Alcohol Clinical And Experimental Research 1999, 23: 1336. DOI: 10.1097/00000374-199908000-00007.Peer-Reviewed Original ResearchAlcohol-dependent patientsHealthy controlsEndorphin levelsCSF levelsMonoamine metabolitesCSF measuresHealthy subjectsNorepinephrine metabolite MHPGLower CSF levelsBeta-endorphin levelsEarly-onset patientsCerebrospinal fluid levelsLate-onset patientsCentral neurotransmitter systemsCSF monoamine metabolitesDopamine metabolite HVAAlcohol cue exposureAlcohol-dependent individualsAlcohol cue reactivityLumbar punctureBackground abnormalitiesMetabolite HVANeurotransmitter systemsMonoaminergic dysregulationMetabolite MHPG