Prenatal Immune Programming of Sex Differences in Dysregulation of Emotion Processing in Midlife
Prenatal Immune Programming of Sex Differences in Dysregulation of Emotion Processing in Midlife
批准号:
9547030
负责人:
JILL M GOLDSTEIN
金额:
$90.17万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-20 至 2018-08-31
关键词:
Adrenal GlandsAdultAffectAgeAgingAmygdaloid structureAnteriorAreaArousalBrainBrain imagingBrain regionCardiacCoupledDataDepressed moodDiagnosisDorsalEarly InterventionEmotional StabilityEmotionsExhibitsExposure toFetal DevelopmentFunctional ImagingFunctional Magnetic Resonance ImagingFunctional disorderGene ExpressionGenotypeGlucocorticoidsGonadal Steroid HormonesHippocampus (Brain)HormonesHumanHydrocortisoneHyperactive behaviorHypothalamic structureImmuneImmune responseImmunologic TestsImmunotherapeutic agentInflammatoryInflammatory ResponseInnate Immune SystemInterleukin-1 betaInterleukin-10Interleukin-6LifeLife ExperienceLinkLongevityMajor Depressive DisorderMeasuresMental DepressionMental disordersMolecularMoodsMultimodal ImagingNational Institute of Mental HealthNatural ImmunityOutcomePathway interactionsPeripheral Blood Mononuclear CellPhenotypePhysiologicalPhysiologyPituitary GlandPrefrontal CortexPregnancyProspective cohortPublic HealthRecruitment ActivityRecurrenceResearch Domain CriteriaRestRiskSex CharacteristicsStimulusStressTNF geneThinnessTimeWomanbrain circuitrycingulate cortexcohortcytokinedisorder riskemotion dysregulationemotion regulationexpectationfetalfetal programmingfunctional declinehealthy agingimaging approachinnovationmenmiddle agemood symptomnegative affectnoveloffspringprenatalprenatal exposureprospectiveresponsesexsymptomatologytranscriptomics
中文摘要
项目总结/文摘
英文摘要
Project Summary/Abstract
Maintaining emotional stability in the face of negative life experiences is critical for healthy aging. Maladaptive
responses to negative affective stimuli (“NAffecS”) are implicated in psychiatric disorders, including major
depressive disorder (MDD). In fact, there are shared brain regions involved in responses to NAffecS and MDD
pathophysiology, including: hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), anterior cingulate
cortex (ACC), and ventromedial and orbital prefrontal cortices (vmPFC, OFC), areas that are highly sexually
dimorphic. Activity in this circuitry is physiologically associated with cortisol response, loss of parasympathetic
cardiac tone, and immune responses, including TNF-α, IL-1β, IL-6, all of which differ by sex. We will test here
that immune pathway abnormalities, beginning in fetal development, are associated with sex-dependent
impacts on HYPO, HIPP, AMYG and PFC, resulting in maladaptive negative emotion processing and
MDD/depressed mood symptomatology in early midlife, the latter of which will accelerate aging of this circuitry
and negative emotion dysregulation in later midlife. We are uniquely poised to examine this for the first time in
humans using data from our 55-year prospective prenatal cohort followed since 2nd/3rd trimesters of gestation
and assessed at ages 44-50 in a previous NIMH study. Over 4 years, we will re-recruit 160 of these offspring
who, 11 years later, will be ages 55-61, and relate maternal prenatal immune activity (TNF-α, IL-1β, IL-6, IL-10)
to sex differences in midlife NAffec circuitry decline and negative emotion processing dysregulation and the
impact of MDD/severe mood symptomatology in early midlife. We will use the same multimodal imaging
approach as previously (structural, functional imaging (sMRI/fMRI)) coupled with hormones, autonomic and
immune physiology, and emotion regulation measures. Novel transcriptomic analyses in the offspring's
peripheral blood mononuclear cells (PBMCs; measuring innate immune gene expression) will be related to
adult midlife outcomes. Our lifespan perspective is an innovative approach to identify potential
immunotherapeutic targets for maintaining healthy emotion processing that are sex-dependent and can be
applied prior to functional decline. This will contribute to RDoC Negative Affect and Arousal phenotypes,
physiology and genotypes, and impact of mood and sex.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Impact of sex differences in immune function on shared risk for cardiometabolic disorder & Alzheimer's disease
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批准号:10300822
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项目类别:
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资助金额:$378.85万
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财政年份:2021
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负责人:JILL M GOLDSTEIN
-
依托单位:
Impact of Sex on Prenatal Stress-Immune Programming of Depression and Autonomic Dysregulation
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批准号:10349463
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项目类别:
-
资助金额:$56.24万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Leadership Administrative Core
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批准号:10540780
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项目类别:
-
资助金额:$14.51万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Leadership Administrative Core
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批准号:10089490
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项目类别:
-
资助金额:$14.73万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
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批准号:10747460
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项目类别:
-
资助金额:$6.22万
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财政年份:2020
-
负责人:JILL M GOLDSTEIN
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依托单位:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
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批准号:10349458
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项目类别:
-
资助金额:$160.15万
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财政年份:2020
-
负责人:JILL M GOLDSTEIN
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依托单位:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
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批准号:10089485
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项目类别:
-
资助金额:$162.33万
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财政年份:2020
-
负责人:JILL M GOLDSTEIN
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依托单位:
Impact of Sex on Prenatal Stress-Immune Programming of Depression and Autonomic Dysregulation
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批准号:10089493
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项目类别:
-
资助金额:$56.29万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Building a Translational Workforce Innovation Network (TWIN)
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批准号:10864217
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项目类别:
-
资助金额:$49.21万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Leadership Administrative Core
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批准号:10349460
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项目类别:
-
资助金额:$14.16万
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财政年份:2020
-
负责人:JILL M GOLDSTEIN
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依托单位:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
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批准号:10527864
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项目类别:
-
资助金额:$7.92万
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财政年份:2020
-
负责人:JILL M GOLDSTEIN
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依托单位:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
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批准号:10540779
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项目类别:
-
资助金额:$159.94万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Impact of Sex on Prenatal Stress-Immune Programming of Depression and Autonomic Dysregulation
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批准号:10540798
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项目类别:
-
资助金额:$60.61万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Leadership Administrative Core
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批准号:10875766
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项目类别:
-
资助金额:$49.21万
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财政年份:2020
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负责人:JILL M GOLDSTEIN
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依托单位:
Impact of Depression on Alzheimer's disease: Prenatal Immune Origins and Shared Impact of Sex
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批准号:10408710
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项目类别:
-
资助金额:$152.93万
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财政年份:2019
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负责人:JILL M GOLDSTEIN
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依托单位:
Impact of Depression on Alzheimer's disease: Prenatal Immune Origins and Shared Impact of Sex
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批准号:10649666
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项目类别:
-
资助金额:$124.02万
-
财政年份:2019
-
负责人:JILL M GOLDSTEIN
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依托单位:
Impact of Depression on Alzheimer's disease: Prenatal Immune Origins and Shared Impact of Sex
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批准号:10020902
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项目类别:
-
资助金额:$143.98万
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财政年份:2019
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负责人:JILL M GOLDSTEIN
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依托单位:
Aging of Emotion Circuitry: Impact of Sex, Depression, and Fetal Immune Origins
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批准号:9884528
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项目类别:
-
资助金额:$70.5万
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财政年份:2018
-
负责人:JILL M GOLDSTEIN
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依托单位:
Aging of Emotion Circuitry: Impact of Sex, Depression, and Fetal Immune Origins
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批准号:10361427
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项目类别:
-
资助金额:$70.59万
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财政年份:2018
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负责人:JILL M GOLDSTEIN
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依托单位:
Aging of Emotion Circuitry: Impact of Sex, Depression, and Fetal Immune Origins
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批准号:10116240
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项目类别:
-
资助金额:$70.44万
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财政年份:2018
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负责人:JILL M GOLDSTEIN
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依托单位:
海外基金