Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
重度抑郁症的性别差异:产前压力免疫和自主神经失调的影响
基本信息
- 批准号:10089485
- 负责人:
- 金额:$ 162.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:Adrenal GlandsAdult ChildrenAmygdaloid structureAnteriorAnxietyAreaAttenuatedAutonomic DysfunctionAutonomic nervous systemBasic ScienceBiological MarkersBrainBrain DiseasesBrain imagingCRH geneCardiacCardiovascular DiseasesCenters of Research ExcellenceClinicalClinical InvestigatorClinical ResearchCollaborationsCommunitiesCorticotropin-Releasing HormoneCoupledCytokine ReceptorsData AnalyticsDevelopmentDevicesDiseaseEarly InterventionElderlyFacultyFetal DevelopmentFunctional disorderGenesGlucocorticoid ReceptorGlucocorticoidsGonadal Steroid HormonesHealthHeartHeart DiseasesHippocampus (Brain)Hormone secretionHormonesHydrocortisoneHypothalamic structureImmuneImmune responseInterleukin-1Interleukin-6KnowledgeLeadershipLifeLongevityMajor Depressive DisorderMapsMedicalMedicineMental DepressionMissionMoodsMyocardial IschemiaNerveNeuronsNeurosciencesOutcomePathway interactionsPeripheralPhysiologicalPhysiologyPituitary GlandPolicy MakerPopulationPrefrontal CortexPublic HealthReceptor ActivationRecurrenceResourcesRiskRodent ModelScientistSeriesSex DifferencesSexual DysfunctionSpecialized CenterSteroid ReceptorsStressStudy modelsTNF geneTechnical ExpertiseTechnologyTestingTherapeuticTrainingTranslatingTranslationsWomanbiological adaptation to stressbrain circuitrycareercingulate cortexclinical effectcomorbid depressioncytokinedepressive symptomsdisabilityearly detection biomarkerseffective therapyheart functionhigh riskimmune functionin uteromenmiddle agemortality riskneuroregulationneurovascularnext generationnovel therapeuticsparaventricular nucleuspedagogyprenatalprenatal stressrespiratoryresponsesexsexual dimorphismstress reactivitysuccesstherapeutic developmenttranslational studyvagus nerve stimulation
项目摘要
OVERALL SUMMARY. Major depressive disorder (MDD) topped heart disease as the number one cause of
disability worldwide, and women have twice the risk of men. MDD is associated with abnormalities in the stress
response circuitry, areas that are among the most sexually dimorphic in the brain. These areas are dense in
sex steroid and glucocorticoid receptors coupled with cytokine receptors. Further, activity in these areas has
been associated with cortisol response, autonomic dysfunction, and immune responses, which we showed
differed by sex. This is important since autonomic dysregulation is significantly associated with cardiovascular
disease. In fact, women are at twice the risk for the co-occurrence of MDD, autonomic dysregulation and heart
disease, leading to a 3-5-fold risk of death in women from heart disease, often with unrecognized and
untreated MDD. Thus, understanding early biomarkers for sex differences in MDD and autonomic
dysregulation will provide knowledge for early intervention, attenuating later life disability, in particular for
women who are at higher risk. The scientific mission of this SCORE is to identify stress-immune pathway
abnormalities, beginning in fetal development, that have shared consequences for sex differences in brain
circuitry regulating mood and lifelong recurrent MDD and dysregulation of hormone and immune responses to
stress, and autonomic and neurovascular dysfunction in early midlife. We aim to facilitate transdisciplinary,
translational collaboration among basic and clinical investigators to enhance our understanding of the impact of
sex on MDD and central and peripheral autonomic function and provide the groundwork for translating this
knowledge into sex-selective therapeutics. Further, we aim to serve as an interdisciplinary resource to train
and disseminate findings about sex differences in MDD and autonomic dysregulation to the scientific and
medical communities, policy makers, and the public. To accomplish this, three integrated studies are proposed:
1) a clinical population neuroscience study relating prenatal risk biomarkers to sex differences in brain circuitry
and physiologic deficits in response to stress in MDD in early midlife; 2) clinical study using direct
transcutaneous neuromodulatory stimulation of the vagus nerve, auricular branch (or taVNS) to target the
circuitry associated with stress-immune function and map its neuroanatomic, physiologic and clinical effects in
MDD by sex, in the same subjects as in project 1; and 3) rodent model studies that will map out the central
mechanistic pathways involved in projects 1 and 2. In addition, three cores will contribute to the success of this
SCORE: 1) Leadership Administration Core to administer and oversee the administrative integration of the
studies and cores; 2) Resources Core to provide shared technical expertise across studies; and 3) Career
Enhancement Core, to supplement the training of junior faculty and others on the topic of our SCORE, and
become pedagogical ambassadors to the scientific, medical and public communities about sex differences in
depression and comorbidities with general medicine, a topic with global public health implications.
整体总结。重度抑郁症(MDD)超过心脏病,成为导致死亡的头号原因
项目成果
期刊论文数量(0)
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JILL M GOLDSTEIN其他文献
JILL M GOLDSTEIN的其他文献
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{{ truncateString('JILL M GOLDSTEIN', 18)}}的其他基金
Impact of sex differences in immune function on shared risk for cardiometabolic disorder & Alzheimer's disease
免疫功能性别差异对心脏代谢疾病共同风险的影响
- 批准号:
10300822 - 财政年份:2021
- 资助金额:
$ 162.33万 - 项目类别:
Impact of Sex on Prenatal Stress-Immune Programming of Depression and Autonomic Dysregulation
性别对抑郁症和自主神经失调的产前应激免疫编程的影响
- 批准号:
10349463 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
重度抑郁症的性别差异:产前压力免疫和自主神经失调的影响
- 批准号:
10747460 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
重度抑郁症的性别差异:产前压力免疫和自主神经失调的影响
- 批准号:
10349458 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
Impact of Sex on Prenatal Stress-Immune Programming of Depression and Autonomic Dysregulation
性别对抑郁症和自主神经失调的产前应激免疫编程的影响
- 批准号:
10089493 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
Building a Translational Workforce Innovation Network (TWIN)
建立转化型劳动力创新网络(TWIN)
- 批准号:
10864217 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
重度抑郁症的性别差异:产前压力免疫和自主神经失调的影响
- 批准号:
10527864 - 财政年份:2020
- 资助金额:
$ 162.33万 - 项目类别:
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