Arie Kaffman, MD, PhD
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About
Titles
Associate Professor of Psychiatry
Biography
Dr. Kaffman is a physician-scientist who works as a psychiatrist at the Newington VA, where he treats a large number of veterans with PTSD. He also has a basic neuroscience lab at Yale, where he studies the impact of early life adversity (ELA) on neurodevelopment and complex behavior in mice. Dr. Kaffman is a Principal Investigator on several NIH-funded grants that integrate molecular/cellular, genomic, pharmacological, and behavioral approaches with imaging techniques such as resting state fMRI and high-resolution dMRI conducted in rodents. This translational approach allows for a direct comparison between findings in rodents and human studies. The objective of this translational research is to elucidate the impact of early adversity on the neurodevelopment of circuits that regulate psychiatrically relevant behaviors, and to utilize this knowledge in the development of novel diagnostic and treatment modalities.
Appointments
Psychiatry
Associate Professor on TermPrimary
Other Departments & Organizations
Education & Training
- Residency
- Yale University School of Medicine (2005)
- MD
- University of California/San Francisco (2001)
- PhD
- University of California San Francisco, Biochemistry and Cell Biology (1999)
Research
Publications
2024
Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity
Ahmed S, Polis B, Jamwal S, Sanganahalli B, MacDowell Kaswan Z, Islam R, Kim D, Bowers C, Giuliano L, Biederer T, Hyder F, Kaffman A. Transient impairment in microglial function causes sex-specific deficits in synaptic maturity and hippocampal function in mice exposed to early adversity. Brain Behavior And Immunity 2024, 122: 95-109. PMID: 39134183, PMCID: PMC11402597, DOI: 10.1016/j.bbi.2024.08.010.Peer-Reviewed Original ResearchEarly-life adversityModel of early-life adversityContextual fear conditioningLimited beddingFear conditioningSynaptic engulfmentLB miceSynaptic pruningSex-specific deficitsHippocampus of maleSex-specific effectsHippocampal deficitsAdolescent miceHippocampal functionEarly adversityChemogenetic activationSynaptic connectionsBehavioral aberrationsPotential compensatory mechanismsSynaptic abnormalitiesHippocampusAblation of microgliaRodent hippocampusDeficitsWeeks of lifeMicroglia: The Drunken Gardeners of Early Adversity
Ahmed S, Polis B, Kaffman A. Microglia: The Drunken Gardeners of Early Adversity. Biomolecules 2024, 14: 964. PMID: 39199352, PMCID: PMC11353196, DOI: 10.3390/biom14080964.Peer-Reviewed Original ResearchEarly life adversityAbnormal immune responseImpact of early life adversityHistory of early life adversityRodent studiesImmune responseNegative childhood experiencesConditions in adulthoodLevels of inflammatory cytokinesLong-term alterationsRefractory responses to treatmentAbnormal brain developmentMicroglial functionResponse to treatmentTraumatic brain injuryResident immune cellsStress reactivityEarly adversityLife adversitySubstance useChildhood experiencesMicroglial inflammatory responseImmune cellsIn adulthoodPeriod of developmentEarly 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 CAUSES SEX-SPECIFIC DEFICITS IN ENTORHINAL-DORSAL HIPPOCAMPUS CONNECTIVITY AND CONTEXTUAL FEAR CONDITIONING IN ADOLESCENT MICE
Islam R, Arefin T, White J, Polis B, Ahmed S, Liu X, Zhang J, Kaffman A. EARLY ADVERSITY CAUSES SEX-SPECIFIC DEFICITS IN ENTORHINAL-DORSAL HIPPOCAMPUS CONNECTIVITY AND CONTEXTUAL FEAR CONDITIONING IN ADOLESCENT MICE. IBRO Neuroscience Reports 2023, 15: s103-s104. DOI: 10.1016/j.ibneur.2023.08.089.Peer-Reviewed Original ResearchEarly 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
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 mazeWhite-Matter Repair as a Novel Therapeutic Target for Early Adversity
Islam R, Kaffman A. White-Matter Repair as a Novel Therapeutic Target for Early Adversity. Frontiers In Neuroscience 2021, 15: 657693. PMID: 33897364, PMCID: PMC8062784, DOI: 10.3389/fnins.2021.657693.Peer-Reviewed Original ResearchMyelin developmentWhite matter repairNovel therapeutic targetPre-clinical workNovel therapeutic interventionsNon-human primatesNew agentsTherapeutic targetAnimal modelsTherapeutic interventionsTranslational researchEarly adversityRecent mechanistic studiesMolecular mechanismsRodentsDiverse mammalian species
News & Links
Media
Microglia from normally developing mouse brain are large highly ramified cells containing large number of synaptic puncta (red dots), Indicating efficient removal of non-functional synapses in the developing hippocampus. In contrast, mice exposed to early life adversity are smaller and contain fewer synaptic puncta. For more details, see Dayanada et.al. 2023, DOI: 10.1016/j.bbi.2022.09.014.
(A) The number of microglia and their size increases from P12-21 in the hippocampus. During this critical period, expression of TREM2 on microglia increases allowing for efficient removal of non-functional synapses labeled with “eat me signals”. This process ensures the formation of more efficient network characterized by high maturity index and is necessary for normal hippocampal function. (B) Exposure to LB reduces TREM2 expression and impairs synaptic pruning during the 2nd and third weeks of life. (C) As a result, adolescent LB mice have reduced maturity index calculated as the ratio between mature mushroom spines (green) and immature spines such as stubby, thin and filopodia (purple, blue, red). For more details, see Dayanada et.al. 2023, DOI: 10.1016/j.bbi.2022.09.014.
- In this study we show that exposure to unpredictable complex stress early in life (UPS) causes more significant anxiety-like behavior compared to the predictable and less severe stress limited bedding or LB. Further, the anxiety behavior is more pronounced in males compared to females. For more details see Johnson et al 2018 doi: 10.1038/s41398-018-0092-z.
- Unpredictable postnatal stress (UPS) causes volumetric and fractional anisotropy changes that resemble those reported in humans and were seen in both males and females. Interestingly, UPS causes sex specific in fronto-limbic connectivity and microglial function in males and females. For more details see White et al. 2020, doi: 10.7554/eLife.58301
Reelin-positive cells project from the lateral entorhinal cortex (LEC) to the dorsal hippocampus via the perforant pathway. These connections are essential for normal hippocampal dependent memory and development. We recently found that these projections fail to form in adolescent male, but not female mice exposed to limited bedding (LB). For additional details see https://www.biorxiv.org/content/10.1101/2023.08.08.552517v1.
News
- October 03, 2011
Sociability may depend upon brain cells generated in adolescence
- October 01, 2006
Grants and contracts awarded to Yale School of Medicine
- July 20, 2004
NARSAD Funds 11 Yale University and Affiliated Researchers