2022
Prefrontal 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
Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers
Kantrowitz JT, Grinband J, Goff DC, Lahti AC, Marder SR, Kegeles LS, Girgis RR, Sobeih T, Wall MM, Choo TH, Green MF, Yang YS, Lee J, Horga G, Krystal JH, Potter WZ, Javitt DC, Lieberman JA. Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers. Neuropsychopharmacology 2020, 45: 1842-1850. PMID: 32403118, PMCID: PMC7608251, DOI: 10.1038/s41386-020-0706-z.Peer-Reviewed Original ResearchConceptsDorsal anterior cingulate cortexBrief Psychiatric Rating ScaleTS-134Target engagementHealthy volunteersMetabotropic glutamate receptor 2/3 agonistKetamine-induced psychotic symptomsBPRS positive symptomsDouble-blind conditionsProof of mechanismKetamine-induced changesAntipsychotic drug developmentTreatment of schizophreniaPsychiatric Rating ScaleAnterior cingulate cortexPrimary outcomeClinical symptomsGlutamatergic drugsGlutamate neurotransmissionTotal symptomsClinical assessmentLow dosePsychotic symptomsHigh dosePlacebo data
2018
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot study
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 imaging
2016
Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies
Averill LA, Purohit P, Averill CL, Boesl MA, Krystal JH, Abdallah CG. Glutamate dysregulation and glutamatergic therapeutics for PTSD: Evidence from human studies. Neuroscience Letters 2016, 649: 147-155. PMID: 27916636, PMCID: PMC5482215, DOI: 10.1016/j.neulet.2016.11.064.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPsychiatric disordersStress-related psychiatric disordersAlternative pharmacologic treatmentsPutative neurobiological underpinningsGlutamate-modulating agentsTrauma-related disordersGlutamatergic abnormalitiesGlutamate dysregulationPharmacologic treatmentPharmacologic interventionsGlutamatergic functionGlutamate neurotransmissionMillions of individualsHuman studiesCardinal featuresStress disorderDisordersNeurobiological underpinningsRelated future directionsEvidenceChronicDysfunctionNeurotransmissionSubject data
2008
Capitalizing on Extrasynaptic Glutamate Neurotransmission to Treat Antipsychotic-Resistant Symptoms in Schizophrenia
Krystal JH. Capitalizing on Extrasynaptic Glutamate Neurotransmission to Treat Antipsychotic-Resistant Symptoms in Schizophrenia. Biological Psychiatry 2008, 64: 358-360. PMID: 18694665, DOI: 10.1016/j.biopsych.2008.06.011.Peer-Reviewed Original Research
2006
Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms
Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary Evidence of Riluzole Efficacy in Antidepressant-Treated Patients with Residual Depressive Symptoms. Biological Psychiatry 2006, 61: 822-825. PMID: 17141740, PMCID: PMC2754299, DOI: 10.1016/j.biopsych.2006.08.037.Peer-Reviewed Original ResearchConceptsHamilton Depression Rating ScaleHamilton Anxiety Rating ScaleTreatment-resistant depressionMajor depressive disorderHARS scoresRating ScaleExcessive glutamatergic neurotransmissionEffects of riluzoleDepression Rating ScaleResidual depressive symptomsAnxiety Rating ScaleRiluzole efficacyMedication regimenAugmentation therapyContinuation phaseAntidepressant activityGlutamate neurotransmissionGlutamatergic neurotransmissionDepressive disorderAnxiolytic effectsDepressive symptomsRiluzolePatientsFirst weekLinear mixed models
2003
Clinical Studies Implementing Glutamate Neurotransmission in Mood Disorders
SANACORA G, ROTHMAN DL, MASON G, KRYSTAL JH. Clinical Studies Implementing Glutamate Neurotransmission in Mood Disorders. Annals Of The New York Academy Of Sciences 2003, 1003: 292-308. PMID: 14684453, DOI: 10.1196/annals.1300.018.Peer-Reviewed Original Research