2025
Novel Approaches for Treating Anxiety and Trauma-Related Disorders
Kaye A, Jefferson S, Krystal J. Novel Approaches for Treating Anxiety and Trauma-Related Disorders. 2025, 583-598. DOI: 10.1093/med/9780197640654.003.0043.Peer-Reviewed Original ResearchNeural plasticityNeural circuitsAnxiety spectrum disordersTreatment-resistant populationModulation of neural circuitsExtinction learningFear extinctionBurden of anxietyThreat responsesTreat anxietyPsychedelic drugsSpectrum disorderImprove anxietyAnxietyPathological perceptionCurrent treatmentReceptor targetsPsychotherapyAntidepressantsAnxiolyticsExtinctionDisordersKetaminePlasticityTreatment
2024
Pharmacological stimulation of infralimbic cortex after fear conditioning facilitates subsequent fear extinction
Bayer H, Hassell J, Oleksiak C, Garcia G, Vaughan H, Juliano V, Maren S. Pharmacological stimulation of infralimbic cortex after fear conditioning facilitates subsequent fear extinction. Neuropsychopharmacology 2024, 49: 1951-1957. PMID: 39138373, PMCID: PMC11480363, DOI: 10.1038/s41386-024-01961-9.Peer-Reviewed Original ResearchMedial prefrontal cortexFear conditioningConditioned freezingConditioned stimulusExtinction of conditioned fear memoryConsolidation of fear conditioningExtinction of conditioned fearAuditory conditioned stimulusConditioned fear memoryGABAA receptor antagonistExtinction trainingExtinction learningPicrotoxin infusionConditioned fearFear extinctionInfralimbic cortexPrefrontal cortexFear suppressionInhibitory memoryFear memoryExtinction retrievalPicrotoxin injectionNeuronal plasticityFemale ratsReceptor antagonistPsilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors
Woodburn S, Levitt C, Koester A, Kwan A. Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors. ACS Chemical Neuroscience 2024, 15: 3034-3043. PMID: 39087917, PMCID: PMC12166970, DOI: 10.1021/acschemneuro.4c00279.Peer-Reviewed Original ResearchPost-traumatic stress disorderFear extinctionFear renewalExtinction retentionSerotonin receptorsPsilocybin effectsEffects of psilocybinExtinction-based therapiesProlonged exposure therapyFear conditioning paradigmAnalysis of sex differencesEnhanced fear extinctionFear learning paradigmAdministration of psilocybinConditioning paradigmExposure therapyFear learningStress disorderClassic psychedelicsPsilocybinSex differencesExtinction experimentsReceptor antagonismDrug effectsSerotoninAn investigation of the role of estradiol in fear reduction during a single session of exposure therapy
Levy H, Mullins J, Tolin D. An investigation of the role of estradiol in fear reduction during a single session of exposure therapy. Cognitive Behaviour Therapy 2024, 53: 364-376. PMID: 38299480, DOI: 10.1080/16506073.2024.2313743.Peer-Reviewed Original ResearchObsessive-compulsive disorderExposure therapyAnxiety disordersPrimary obsessive-compulsive disorderSubjective distress ratingsAnxiety specialty clinicLow estradiol groupFear extinctionSubjective distressFear reductionExposure sessionsBrief delayDistress ratingsRecall delayAnxietyTherapy researchExposure outcomesDisordersSpecialty clinicsHigher estradiolDistressPrimary diagnosisEndogenous estradiolRecallEstradiol group
2022
Mechanisms of Action in Exposure Therapy
Knowles K, Tolin D. Mechanisms of Action in Exposure Therapy. Current Psychiatry Reports 2022, 24: 861-869. PMID: 36399234, DOI: 10.1007/s11920-022-01391-8.Peer-Reviewed Original ResearchConceptsExposure-based interventionsExposure therapyReturn of fearAnxiety-related disordersExtinction learningFear extinctionNeural levelPrefrontal regionsNeurobiological mechanismsSafety behaviorSuch translational researchTherapy workPromising future directionsBehavioral mechanismsPharmacological augmentationMixed resultsBehavioral changesIncreased activationFull symptom reliefMultiple levelsFuture directionsRecent FindingsRecent studiesSymptom improvementMechanism of actionSymptom reliefPositive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale mice
2021
Escitalopram modulates learning content-specific neuroplasticity of functional brain networks
Klöbl M, Seiger R, Vanicek T, Handschuh P, Reed MB, Spurny-Dworak B, Ritter V, Godbersen GM, Gryglewski G, Kraus C, Hahn A, Lanzenberger R. Escitalopram modulates learning content-specific neuroplasticity of functional brain networks. NeuroImage 2021, 247: 118829. PMID: 34923134, DOI: 10.1016/j.neuroimage.2021.118829.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexSelective serotonin reuptake inhibitorsPrefrontal cortexBroca's areaLingual gyrusFunctional connectivityFunctional magnetic resonance imagingResting-state functional magnetic resonance imagingFunctional brain networksBrain functional connectivityFear extinctionComplexity of learningSerotonin reuptake inhibitorsHuman neuroplasticityBrain networksMagnetic resonance imagingEscitalopram intakeComparable modulationClinical improvementSSRI escitalopramDaily doseReuptake inhibitorsNeuroplastic changesHealthy subjectsNeuroplasticityLow Estradiol May Not Impede Cognitive Restructuring in Women With Anxiety Disorders.
Levy H, Jean A, Ching T, Nett A, Mullins J, Tolin D. Low Estradiol May Not Impede Cognitive Restructuring in Women With Anxiety Disorders. Journal Of Cognitive Psychotherapy 2021, 35: 212-220. PMID: 34362860, DOI: 10.1891/jcpsy-d-20-00038.Peer-Reviewed Original ResearchConceptsCognitive restructuringCognitive reappraisalAnxiety disordersCR taskExtinction-based therapiesSubjective distress ratingsPrimary anxiety disorderSkin conductance responsesLow estradiol groupFear extinctionNegative affectPsychophysiological arousalConductance responsesDistress ratingsCR outcomesCR abilityLow estradiolCR skillsExtinction processPrior researchTaskReappraisalEstradiol groupDisordersAcquisition
2019
Ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans
Meyer HC, Odriozola P, Cohodes EM, Mandell JD, Li A, Yang R, Hall BS, Haberman JT, Zacharek SJ, Liston C, Lee FS, Gee DG. Ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 26970-26979. PMID: 31822612, PMCID: PMC6936350, DOI: 10.1073/pnas.1910481116.Peer-Reviewed Original ResearchCompound cueAnxiety disordersPrelimbic cortexSafety signal learningCurrent evidence-based treatmentsVentromedial prefrontal cortexCognitive behavioral therapyAlternative neural mechanismVentral hippocampal neuronsPresence of threatNeural activity patternsEvidence-based treatmentsAnxious individualsThreat cuesEvidence-based interventionsSafety learningFear extinctionVentral hippocampusThreat responsesSignal learningNeural mechanismsBehavioral therapyInhibition paradigmPrefrontal cortexHippocampal responses
2017
Fear extinction in an obsessive-compulsive disorder animal model: Influence of sex and estrous cycle
Reimer A, de Oliveira A, Diniz J, Hoexter M, Miguel E, Milad M, Brandão M. Fear extinction in an obsessive-compulsive disorder animal model: Influence of sex and estrous cycle. Neuropharmacology 2017, 131: 104-115. PMID: 29225044, DOI: 10.1016/j.neuropharm.2017.12.015.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderFear extinctionOCD patientsTreatment of OCDFear extinction retentionExtinction retention deficitsFear extinction trainingOCD pathophysiologyOCD-like symptomsAnterior cingulate cortexFear inhibitionExtinction retentionAccount sex differencesEstrous cycleExtinction trainingRetention deficitsRepetitive behaviorsDistinct neurotransmitter systemsMedial prefrontalUntreated OCD patientsCingulate cortexAnimal modelsSelf-grooming behaviorBrain areasEstrous cycle phaseFear extinction and memory reconsolidation as critical components in behavioral treatment for posttraumatic stress disorder and potential augmentation of these processes
Smith NB, Doran JM, Sippel LM, Harpaz-Rotem I. Fear extinction and memory reconsolidation as critical components in behavioral treatment for posttraumatic stress disorder and potential augmentation of these processes. Neuroscience Letters 2017, 649: 170-175. PMID: 28065842, DOI: 10.1016/j.neulet.2017.01.006.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderReconsolidation processPTSD psychotherapyStress disorderBehavioral treatmentExposure-based treatmentsCritical brain regionsFear extinctionMemory reconsolidationTraumatic memoriesImportant future directionsPTSD populationsPTSD therapyNeurobiological mechanismsPrefrontal cortexReconsolidationBrain regionsPsychotherapyProcess of extinctionMemoryPotential avenuesFuture directionsBehavioral modificationExtinctionDisorders
2016
Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders
Lester KJ, Coleman JR, Roberts S, Keers R, Breen G, Bögels S, Creswell C, Hudson JL, McKinnon A, Nauta M, Rapee RM, Schneider S, Silverman WK, Thastum M, Waite P, Wergeland GJ, Eley TC. Genetic variation in the endocannabinoid system and response to Cognitive Behavior Therapy for child anxiety disorders. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2016, 174: 144-155. PMID: 27346075, PMCID: PMC5324578, DOI: 10.1002/ajmg.b.32467.Peer-Reviewed Original ResearchConceptsAnxiety disorder diagnosisIndividual differencesPrimary anxiety disorder diagnosisSuccessful psychological treatmentDisorder diagnosisCognitive behavior therapyAnxiety disorder severityExtinction learningFear extinctionPsychological treatmentBehavior therapyDisorder severityPoor treatment responseSymptom severityEffect sizeFull sampleEndocannabinoid systemFearTreatment responseCBTAnxietyPotential clinical utilityLimited evidenceLearningChildren
2015
Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood
Bhagat SM, Butler SS, Taylor JR, McEwen BS, Strittmatter SM. Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood. Molecular Psychiatry 2015, 21: 1281-1289. PMID: 26619810, PMCID: PMC4887429, DOI: 10.1038/mp.2015.179.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderExtinction trainingFear memorySpontaneous fear recoveryBasolateral amygdalaJuvenile rodentsFear recoveryFear renewalFear extinctionFear expressionInhibitory synapse markersNgR1 expressionStress disorderNogo receptor 1Anxiety disordersInfralimbic cortexCritical periodNeural plasticityMemoryTemporary windowsReceptor 1TrainingAdulthoodNgR1 functionNaive mice
2013
Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies
Buhle JT, Silvers JA, Wager TD, Lopez R, Onyemekwu C, Kober H, Weber J, Ochsner KN. Cognitive Reappraisal of Emotion: A Meta-Analysis of Human Neuroimaging Studies. Cerebral Cortex 2013, 24: 2981-2990. PMID: 23765157, PMCID: PMC4193464, DOI: 10.1093/cercor/bht154.Peer-Reviewed Original ResearchConceptsLateral temporal cortexCognitive reappraisalEmotional respondingTemporal cortexSemantic representationEmotion regulation strategiesCognitive control regionsParietal control regionsVentromedial prefrontal cortexHuman neuroimaging studiesEmotion-related responsesCognitive controlEmotional stimuliFear extinctionAmygdala responseNegative affectRegulation strategiesNeuroimaging studiesBilateral amygdalaPrefrontal cortexAffective impactBrain regionsAttenuate activityAmygdalaReappraisal
2012
Exposure therapy, D-cycloserine, and functional magnetic resonance imaging in patients with snake phobia: a randomized pilot study.
Nave AM, Tolin DF, Stevens MC. Exposure therapy, D-cycloserine, and functional magnetic resonance imaging in patients with snake phobia: a randomized pilot study. The Journal Of Clinical Psychiatry 2012, 73: 1179-86. PMID: 23059145, DOI: 10.4088/jcp.11m07564.Peer-Reviewed Original ResearchConceptsExposure therapyD-cycloserinePhobic stimuliSnake phobiaFunctional magnetic resonance imaging (fMRI) taskRight dorsolateral prefrontal cortexPrefrontal brain activationPrefrontal cortex responsesD-cycloserine augmentationAnterior cingulate activationFunctional magnetic resonanceDorsolateral prefrontal cortexHuman brain functionDifferent neural pathwaysFear extinctionSnake stimuliExposure hierarchyNeural substratesBrain activationCingulate activationNeural responsesEmotional learningPrefrontal cortexCortex responsesPerigenual cingulateP-786 - The neural correlates of aversive learning among PTSD patients
Harpaz-Rotem I, Levy I, Schiller D. P-786 - The neural correlates of aversive learning among PTSD patients. European Psychiatry 2012, 27: 1. DOI: 10.1016/s0924-9338(12)74953-2.Peer-Reviewed Original ResearchFear responsesPTSD patientsUnconditioned stimulusAcquisition of fearAversive unconditioned stimulusContext of PTSDExtinction learningFear acquisitionFear extinctionFear learningNeural correlatesReversal learningAversive learningReversal taskDistinct predictionsReinforcement contingenciesHealthy controlsPTSDFirst CSCombat situationsStimuliLearningGSR dataDiminished abilityContext of war
2008
Increased fear‐ and stress‐related anxiety‐like behavior in mice lacking tuberoinfundibular peptide of 39 residues
Fegley DB, Holmes A, Riordan T, Faber CA, Weiss JR, Ma S, Batkai S, Pacher P, Dobolyi A, Murphy A, Sleeman MW, Usdin TB. Increased fear‐ and stress‐related anxiety‐like behavior in mice lacking tuberoinfundibular peptide of 39 residues. Genes Brain & Behavior 2008, 7: 933-942. PMID: 18700839, PMCID: PMC2605196, DOI: 10.1111/j.1601-183x.2008.00432.x.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorAnxiety-related behaviorTuberoinfundibular peptideElevated plus-maze assayParathyroid hormone 2 receptorMedial paralemniscal nucleusGreater anxiety-like behaviorPavlovian fear conditioning paradigmShock-probe testGroups of neuronsMedial prefrontal cortexSubparafascicular areaNeurons projectAnxiety-related phenotypesLateral brainstemParalemniscal nucleusLateral septumBed nucleusStria terminalisFear conditioning paradigmEnvironmental provocationTargeted null mutationBrain regionsFear extinctionPrefrontal cortexA History of Corticosterone Exposure Regulates Fear Extinction and Cortical NR2B, GluR2/3, and BDNF
Gourley SL, Kedves AT, Olausson P, Taylor JR. A History of Corticosterone Exposure Regulates Fear Extinction and Cortical NR2B, GluR2/3, and BDNF. Neuropsychopharmacology 2008, 34: 707-716. PMID: 18719621, PMCID: PMC3679657, DOI: 10.1038/npp.2008.123.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderConditioned fearFear memory acquisitionFear extinction trainingVentromedial prefrontal cortexContextual fear conditioningMedial orbitofrontal cortexPrior chronic exposureExtinction learningFear extinctionExtinction trainingFear conditioningFear statesImpairs extinctionStress disorderBehavioral flexibilityMemory acquisitionOrbitofrontal cortexPrefrontal cortexNeural systemsAMPA receptor subunitsCortical regionsActive learning processPrior stressGlucocorticoid exposureA Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy
Norberg MM, Krystal JH, Tolin DF. A Meta-Analysis of D-Cycloserine and the Facilitation of Fear Extinction and Exposure Therapy. Biological Psychiatry 2008, 63: 1118-1126. PMID: 18313643, DOI: 10.1016/j.biopsych.2008.01.012.Peer-Reviewed Original ResearchConceptsExposure therapyFear extinctionD-cycloserineNMDA receptor functionPartial N-methyl-d-aspartate (NMDA) receptor agonistEffects of DCsExposure-based therapyExposure-based treatmentsFear memory consolidationReceptor functionN-methyl-D-aspartate receptor agonistMemory consolidationDCS doseTranslational researchExposure procedureTherapy literatureEnglish-language journal articlesReceptor agonistQuantitative reviewTrial designMeta-analysisTherapyStudy authorsTypes of subjectsEffective agent
2006
Neurobiology of anxiety disorders and implications for treatment.
Garakani A, Mathew SJ, Charney DS. Neurobiology of anxiety disorders and implications for treatment. Annals Of Global Health 2006, 73: 941-9. PMID: 17195879.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPost-traumatic stress disorderCognitive behavioral therapyFear conditioningUnconditioned stimulusAnxiety disordersPartial NMDA agonistFear inhibitionFear extinctionTraumatic memoriesFear circuitryFear responsesPavlovian conditioningBehavioral therapyStress disorderSpecific phobiaNew learningAmygdala pathwayD-cycloserineAnti-anxiety treatmentPanic disorderPreliminary evidenceStimuliMemoryN-methyl-D-aspartate antagonistsNeurobiology
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