2021
Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging
Arefin TM, Lee CH, White JD, Zhang J, Kaffman A. Macroscopic Structural and Connectome Mapping of the Mouse Brain Using Diffusion Magnetic Resonance Imaging. Bio-protocol 2021, 11: e4221. PMID: 34909442, PMCID: PMC8635841, DOI: 10.21769/bioprotoc.4221.Peer-Reviewed Original ResearchEarly life stressMagnetic resonance imagingMouse brainDiffusion magnetic resonance imagingMouse modelResonance imagingWhole-brain voxel-based analysisVoxel-based analysisClinical trialsPostnatal stressPreclinical studiesNeurological conditionsAdult miceEntire mouse brainStructural abnormalitiesBrain regionsMouse strainsBrain connectivityBrainLife stressTranslational utilityStructural connectivityRodentsMiceTranslational workEditorial: Effects of Early Life Stress on Neurodevelopment and Health: Bridging the Gap Between Human Clinical Studies and Animal Models
Kaffman A, Herringa RJ, Sanchez MM. Editorial: Effects of Early Life Stress on Neurodevelopment and Health: Bridging the Gap Between Human Clinical Studies and Animal Models. Frontiers In Human Neuroscience 2021, 15: 751102. PMID: 34675791, PMCID: PMC8523778, DOI: 10.3389/fnhum.2021.751102.Peer-Reviewed Original ResearchDeficits 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
The Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models
White JD, Kaffman A. The Moderating Effects of Sex on Consequences of Childhood Maltreatment: From Clinical Studies to Animal Models. Frontiers In Neuroscience 2019, 13: 1082. PMID: 31680821, PMCID: PMC6797834, DOI: 10.3389/fnins.2019.01082.Peer-Reviewed Original ResearchEarly life stress
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 proteins
2014
Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function in mood and anxiety disorders
Coplan JD, Fulton SL, Reiner W, Jackowski A, Panthangi V, Perera TD, Gorman JM, Huang YY, Tang CY, Hof PR, Kaffman A, Dwork AJ, Mathew SJ, Kaufman J, Mann JJ. Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function in mood and anxiety disorders. Frontiers In Behavioral Neuroscience 2014, 8: 440. PMID: 25566007, PMCID: PMC4274982, DOI: 10.3389/fnbeh.2014.00440.Peer-Reviewed Original ResearchEarly life stressRight hippocampal volumeHippocampal volumeCerebrospinal fluidFractional anisotropySerotonin neurotransmissionMonoamine metabolitesNeurotrophic activitySmaller right hippocampal volumeAnxiety disordersHigh cerebrospinal fluidElevated cerebrospinal fluidWhite matter fractional anisotropyEffects of ELSLife stressMonths of ageReduced fractional anisotropyWM fractional anisotropySerotonin deficitVFD subjectsDorsal rapheMacaque modelCSF tapsInternal capsuleNeurotrophic effectsEarly 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 growthEarly life stress and macaque amygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene
Coplan JD, Fathy HM, Jackowski AP, Tang CY, Perera TD, Mathew SJ, Martinez J, Abdallah CG, Dwork AJ, Pantol G, Carpenter D, Gorman JM, Nemeroff CB, Owens MJ, Kaffman A, Kaufman J. Early life stress and macaque amygdala hypertrophy: preliminary evidence for a role for the serotonin transporter gene. Frontiers In Behavioral Neuroscience 2014, 8: 342. PMID: 25339875, PMCID: PMC4186477, DOI: 10.3389/fnbeh.2014.00342.Peer-Reviewed Original ResearchLarger amygdala volumesAmygdala volumeSerotonin transporter geneFractional anisotropyCerebrospinal fluid concentrationsEarly life stressRight amygdala volumeAnxiety-like responsesHippocampal neurogenesisInternal capsuleAnterior limbMRI scansLeft amygdalaSecondary analysisFluid concentrationsYoung adulthoodTransporter geneLife stressNeurobiological parametersPersistent changesHypertrophyPreliminary evidenceShort alleleAdulthoodStress-related variables
2011
Early 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 developmentEarly-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 ResearchConceptsAnxiety-like behaviorEarly life stressPostnatal maternal careMaternal carePostnatal periodLife stress