2024
Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice
Islam R, White J, Arefin T, Mehta S, Liu X, Polis B, Giuliano L, Ahmed S, Bowers C, Zhang J, Kaffman A. Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice. Biology Of Sex Differences 2024, 15: 39. PMID: 38715106, PMCID: PMC11075329, DOI: 10.1186/s13293-024-00616-0.Peer-Reviewed Original ResearchConceptsLateral entorhinal cortexContextual fear conditioningDorsal hippocampusHippocampal developmentSex differencesFear conditioningEarly adversityLimited beddingSevere deficitsModel of early adversitySex-specific deficitsReelin-positive neuronsPerforant pathwayReelin-positive cellsDiffusion magnetic resonance imagingEx vivo diffusion magnetic resonance imagingContextual freezingContextual memoryAdolescent miceHippocampal functionLife adversityEntorhinal cortexHippocampusDeficitsAdolescent males
2023
Early adversity changes the economic conditions of mouse structural brain network organization
Carozza S, Holmes J, Vértes P, Bullmore E, Arefin T, Pugliese A, Zhang J, Kaffman A, Akarca D, Astle D. Early adversity changes the economic conditions of mouse structural brain network organization. Developmental Psychobiology 2023, 65: e22405. PMID: 37607894, PMCID: PMC10505050, DOI: 10.1002/dev.22405.Peer-Reviewed Original ResearchConceptsEarly adversityStructural brain network organizationPostnatal stressBrain network organizationMental health outcomesEarly life adversityCognitive abilitiesNeural processesLife adversityConnectome organizationAdversityStructural connectomeConnectomeNetwork organizationGenerative processMouse connectomeHealth outcomesLong-distance connectionsOrganizationEffective responseAdaptive mechanismsAbilityStressWiring cost
2022
Early life stress impairs synaptic pruning in the developing hippocampus
Dayananda KK, Ahmed S, Wang D, Polis B, Islam R, Kaffman A. Early life stress impairs synaptic pruning in the developing hippocampus. Brain Behavior And Immunity 2022, 107: 16-31. PMID: 36174883, PMCID: PMC10497209, DOI: 10.1016/j.bbi.2022.09.014.Peer-Reviewed Original ResearchConceptsSynaptic pruningMicroglial ramificationHippocampal functionAbnormal hippocampal functionCA1 pyramidal neuronsExpression of TREM2Increased spine densityRamification of microgliaEarly life adversityNormal hippocampal functionSynaptic engulfmentClinical outcomesPyramidal neuronsSpine densityFemale miceHippocampal stimulationSevere formHippocampal developmentPhagocytic activitySevere impairmentEx vivoLife adversityThird weekEarly adversityMice
2021
Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis
Rocha M, Wang D, Avila-Quintero V, Bloch MH, Kaffman A. Deficits in hippocampal-dependent memory across different rodent models of early life stress: systematic review and meta-analysis. Translational Psychiatry 2021, 11: 231. PMID: 33879774, PMCID: PMC8058062, DOI: 10.1038/s41398-021-01352-4.Peer-Reviewed Original ResearchConceptsEarly life stressNovel object recognitionMorris water mazeDifferent rodent modelsContextual fear conditioningMaternal separationHippocampal-dependent memoryVentral hippocampusDorsal hippocampusRodent modelsLife stressAbnormal hippocampal developmentStandardized mean differenceSimilar cognitive deficitsWeb of ScienceModerate effect sizeCFC taskFunctional deficitsFear conditioningInclusion criteriaPreclinical studiesReduced freezingHippocampal developmentLimited beddingWater maze
2020
Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning
White JD, Arefin TM, Pugliese A, Lee CH, Gassen J, Zhang J, Kaffman A. Early life stress causes sex-specific changes in adult fronto-limbic connectivity that differentially drive learning. ELife 2020, 9: e58301. PMID: 33259286, PMCID: PMC7725504, DOI: 10.7554/elife.58301.Peer-Reviewed Original ResearchConceptsEarly life stressSex-specific changesContextual freezing behaviorFronto-limbic connectivityLife stressHigh-resolution diffusion magnetic resonance imagingSex-specific mechanismsMagnetic resonance imagingNeuroanatomical alterationsPostnatal stressDiffusion magnetic resonance imagingMouse modelFronto-limbicResonance imagingModerate responseMalesTranslational workFemalesRodentsFreezing behaviorHuman imagingImagingHypoconnectivityInjurySystematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents
Wang D, Levine JLS, Avila-Quintero V, Bloch M, Kaffman A. Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents. Translational Psychiatry 2020, 10: 174. PMID: 32483128, PMCID: PMC7264128, DOI: 10.1038/s41398-020-0856-0.Peer-Reviewed Original ResearchConceptsOpen field testEarly life stressSystematic reviewEffects of MSEffects of ELSAnxiety-like behaviorDefensive behaviorAnxiogenic effectsMaternal separationRodent modelsRatsEarly adversityMiceAbility of MSLife stressLack of standardizationChildhood maltreatmentRodentsExploratory behaviorEffect sizeInconsistent resultsELS modelImportant differencesReviewMS protocol
2019
Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development
Kaffman A, White JD, Wei L, Johnson FK, Krystal JH. Enhancing the Utility of Preclinical Research in Neuropsychiatry Drug Development. Methods In Molecular Biology 2019, 2011: 3-22. PMID: 31273690, PMCID: PMC6895673, DOI: 10.1007/978-1-4939-9554-7_1.Peer-Reviewed Original ResearchConceptsPreclinical researchAnimal modelsPsychiatric conditionsLower clinical success ratesClinical success rateCommon psychiatric conditionsPsychiatric clinical trialsClinical trialsNew pharmacotherapiesMore effective interventionsPreclinical workPsychiatric disordersPsychiatric pathophysiologyMental illnessSystematic reviewEffective interventionsAnimal experimentsDrug development processSuccess rateDrug developmentHuman psychopathologyPharmaceutical companiesPredictive validityLarge pharmaceutical companiesAnimals
2018
Amygdala hyper-connectivity in a mouse model of unpredictable early life stress
Johnson FK, Delpech JC, Thompson GJ, Wei L, Hao J, Herman P, Hyder F, Kaffman A. Amygdala hyper-connectivity in a mouse model of unpredictable early life stress. Translational Psychiatry 2018, 8: 49. PMID: 29463821, PMCID: PMC5820270, DOI: 10.1038/s41398-018-0092-z.Peer-Reviewed Original ResearchConceptsEarly life stressAdult male miceAnxiety-like behaviorLimited beddingMale miceMouse modelUnpredictable early life stressAmygdala-prefrontal cortex connectivityChildhood maltreatmentOpen field testFrontolimbic brain regionsResting-state fMRIFrontolimbic connectivityPostnatal stressCortex connectivityAbnormal connectivityAmygdala connectivityAdult miceAnimal modelsFrontolimbic circuitsBrain regionsStress paradigmPrefrontal cortexRobust increaseMice
2017
Early life stress perturbs the function of microglia in the developing rodent brain: New insights and future challenges
Johnson FK, Kaffman A. Early life stress perturbs the function of microglia in the developing rodent brain: New insights and future challenges. Brain Behavior And Immunity 2017, 69: 18-27. PMID: 28625767, PMCID: PMC5732099, DOI: 10.1016/j.bbi.2017.06.008.Peer-Reviewed Original ResearchConceptsEarly life stressMicroglial functionLife stressAnimal modelsBehavioral abnormalitiesStress-induced neuroinflammationMicroglial cell numberFunction of microgliaMicroglial gene expressionChildhood maltreatmentInnate immune systemMedical complicationsLong-term adultAbnormal maturationMouse modelSynaptic pruningRodent brainImmune systemPhagocytic activityAxonal growthBrain developmentDaily separationFirst weekGene expressionAbnormalities
2016
Early life stress perturbs the maturation of microglia in the developing hippocampus
Delpech JC, Wei L, Hao J, Yu X, Madore C, Butovsky O, Kaffman A. Early life stress perturbs the maturation of microglia in the developing hippocampus. Brain Behavior And Immunity 2016, 57: 79-93. PMID: 27301858, PMCID: PMC5010940, DOI: 10.1016/j.bbi.2016.06.006.Peer-Reviewed Original ResearchConceptsEarly life stressHippocampal developmentLife stressPhagocytic activityAbnormal hippocampal developmentNormal hippocampal developmentMorphology of microgliaPostnatal day 28Vivo phagocytic activityImpairs hippocampal functionMaturation of microgliaImmune panelHippocampal microgliaMicroglial activityMicroglial functionNormal cell numbersSynaptic maturationOld miceMicrogliaMouse modelRodent modelsSynaptic pruningDay 28Old pupsHippocampus
2015
Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus
Wei L, Hao J, Lacher RK, Abbott T, Chung L, Colangelo CM, Kaffman A. Early-Life Stress Perturbs Key Cellular Programs in the Developing Mouse Hippocampus. Developmental Neuroscience 2015, 37: 476-488. PMID: 26068561, PMCID: PMC4644446, DOI: 10.1159/000430861.Peer-Reviewed Original ResearchConceptsEarly life stressEffects of ELSHippocampal developmentSynaptic maturationAxonal growthExpression of proteinsJuvenile hippocampusJuvenile miceHippocampal functionAbnormal hippocampal developmentNormal axonal growthHippocampal-dependent memoryNormal synaptic developmentHuman imaging studiesTotal protein contentCA1 neuronsSynaptic markersFemale miceMouse modelMouse hippocampusSynaptic pruningAnimal modeMature spinesHippocampusSynaptic proteinsEarly-Life Stress Restricts the Capacity of Adult Progenitor Cells to Differentiate into Neurons
Kaffman A. Early-Life Stress Restricts the Capacity of Adult Progenitor Cells to Differentiate into Neurons. Biological Psychiatry 2015, 77: 307-309. PMID: 25592267, PMCID: PMC4435555, DOI: 10.1016/j.biopsych.2014.11.008.Peer-Reviewed Original Research
2014
Early Life Stress Inhibits Expression of Ribosomal RNA in the Developing Hippocampus
Wei L, Hao J, Kaffman A. Early Life Stress Inhibits Expression of Ribosomal RNA in the Developing Hippocampus. PLOS ONE 2014, 9: e115283. PMID: 25517398, PMCID: PMC4269428, DOI: 10.1371/journal.pone.0115283.Peer-Reviewed Original ResearchConceptsEarly life stressSecond weekHippocampal growthAbnormal hippocampal functionNormal hippocampal developmentNormal mouse hippocampusLife stressMaternal separationMouse hippocampusMouse modelHippocampal developmentHippocampal functionHippocampus developmentNovel molecular mechanismDaily separationHippocampusWeeksDNA methylationInhibits expressionAdulthoodExposureMolecular mechanismsRNA contentGradual declineNormal growth
2011
New Frontiers in Animal Research of Psychiatric Illness
Kaffman A, Krystal J. New Frontiers in Animal Research of Psychiatric Illness. Methods In Molecular Biology 2011, 829: 3-30. PMID: 22231804, PMCID: PMC3337084, DOI: 10.1007/978-1-61779-458-2_1.Peer-Reviewed Original ResearchConceptsPsychiatric illnessAnimal modelsMental illnessHuman psychopathologyValid animal modelCurrent animal modelsNumerous psychiatric disordersMore effective interventionsResearch Domain Criteria projectInternational ClassificationPsychiatric disordersMeasurable endophenotypesIllnessNeurodevelopmental changesSubstance abuseEffective interventionsAnxiety disordersStatistical ManualMolecular changesDevelopmental originsMental disorders diagnostic systemsCircuit developmentTranslational workAnimal researchBehavioral outcomesEarly Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus
Wei L, Simen A, Mane S, Kaffman A. Early Life Stress Inhibits Expression of a Novel Innate Immune Pathway in the Developing Hippocampus. Neuropsychopharmacology 2011, 37: 567-580. PMID: 21993208, PMCID: PMC3242319, DOI: 10.1038/npp.2011.239.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsAnimals, NewbornAnxietyBehavior, AnimalCarrier ProteinsCorticosteroneCritical Period, PsychologicalDisease Models, AnimalDown-RegulationFemaleGenomicsHippocampusHumansImmunity, InnateMaleMaternal DeprivationMembrane GlycoproteinsMemory DisordersMiceMice, Inbred BALB CMice, KnockoutNeurogenesisStress, PsychologicalConceptsLipopolysaccharide binding proteinEarly life stressAnxiety-like behaviorLife stressSynaptic pruningNovel innate immune pathwayLBP knockout miceNormal hippocampal developmentNormal synaptic pruningSynaptic marker PSD95Hippocampus of pupsMajor risk factorChronic mental illnessImpairs cognitive functionInnate immune pathwaysPostnatal day 30Hippocampal-dependent memoryAbnormal spine morphologyInnate immune systemNon-human primatesLBP levelsSpine densityMicroglia cellsRisk factorsHippocampal developmentAffiliative Behavior Requires Juvenile, But Not Adult Neurogenesis
Wei L, Meaney MJ, Duman RS, Kaffman A. Affiliative Behavior Requires Juvenile, But Not Adult Neurogenesis. Journal Of Neuroscience 2011, 31: 14335-14345. PMID: 21976519, PMCID: PMC3204413, DOI: 10.1523/jneurosci.1333-11.2011.Peer-Reviewed Original ResearchConceptsAdult female miceAdult neurogenesisFemale miceSubventricular zoneAblation of neurogenesisLevels of neurogenesisTransgenic mouse approachSubgranular zoneOlfactory deficitsNew neuronsGlobal eliminationBrain circuitsNeurogenesisProfound impairmentMiceJuvenile periodNovel roleAdult femalesSocial explorationMouse approachSocial abnormalitiesMolecular mechanismsAblationFemalesPeriodEarly-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates
Jackowski A, Perera TD, Abdallah CG, Garrido G, Tang CY, Martinez J, Mathew SJ, Gorman JM, Rosenblum LA, Smith EL, Dwork AJ, Shungu DC, Kaffman A, Gelernter J, Coplan JD, Kaufman J. Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates. Psychiatry Research 2011, 192: 37-44. PMID: 21377844, PMCID: PMC4090111, DOI: 10.1016/j.pscychresns.2010.11.006.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAnxietyBehavior, AnimalBrain MappingCorpus CallosumCross-Sectional StudiesFearGene FrequencyGenotypeHippocampusImage Processing, Computer-AssistedLinear ModelsMacaca radiataMagnetic Resonance ImagingMaleSerotonin Plasma Membrane Transport ProteinsStress, PsychologicalConceptsBrain developmentNonhuman primatesCorpus callosum measurementsMale bonnet monkeysMiddle temporal gyrus volumeCorpus callosum developmentMale nonhuman primatesEarly life stressReduced hippocampusCorpus callosumMRI measuresBonnet monkeysPsychiatric disordersMRI scansHippocampal volumetricsSerotonin transporter genotypeCC sizeStress paradigmHippocampusStress reactivityMorphometry assessmentBehavioral assessmentTransporter genotypeAnxious behaviorEarly stress
2010
Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study
Coplan JD, Abdallah CG, Kaufman J, Gelernter J, Smith EL, Perera TD, Dwork AJ, Kaffman A, Gorman JM, Rosenblum LA, Owens MJ, Nemeroff CB. Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: A pilot study. Psychoneuroendocrinology 2010, 36: 289-293. PMID: 20692103, PMCID: PMC3017732, DOI: 10.1016/j.psyneuen.2010.07.011.Peer-Reviewed Original ResearchConceptsEarly life stressCSF CRF concentrationsCRF concentrationsCerebrospinal fluid corticotropin-releasing factor concentrationsCorticotropin-releasing factor concentrationsPilot studyNonhuman primate modelCorticotropin-releasing factorYears of ageEarly life adversitySerotonin transporter gene polymorphismPersistent elevationTransporter gene polymorphismPrimate modelMajor depressionCSF samplesDepressive symptomsGene polymorphismsAllele groupFactor concentrationsLFD conditionsMale bonnet macaquesChildhood abuseSubsequent developmentBonnet macaquesThe role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates
Coplan JD, Abdallah CG, Tang CY, Mathew SJ, Martinez J, Hof PR, Smith EL, Dwork AJ, Perera TD, Pantol G, Carpenter D, Rosenblum LA, Shungu DC, Gelernter J, Kaffman A, Jackowski A, Kaufman J, Gorman JM. The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates. Neuroscience Letters 2010, 480: 93-96. PMID: 20541590, PMCID: PMC2951885, DOI: 10.1016/j.neulet.2010.06.012.Peer-Reviewed Original ResearchConceptsDeep brain stimulationInternal capsuleDiffusion tensor imagingWhite matterFractional anisotropyAnterior limbNonhuman primate modelWhite matter impairmentAdult male bonnet macaquesOccipital white matterEarly life stressWhite matter tract integrityWhite matter integrityParental verbal abuseMother-infant attachmentPrimate modelPosterior limbBrain stimulationTract integrityTensor imagingAnxiety disordersAnxiety scoresMale bonnet macaquesLife stressSignificant reductionEarly life stress increases anxiety-like behavior in Balbc mice despite a compensatory increase in levels of postnatal maternal care
Wei L, David A, Duman RS, Anisman H, Kaffman A. Early life stress increases anxiety-like behavior in Balbc mice despite a compensatory increase in levels of postnatal maternal care. Hormones And Behavior 2010, 57: 396-404. PMID: 20096699, PMCID: PMC2849915, DOI: 10.1016/j.yhbeh.2010.01.007.Peer-Reviewed Original Research