An RDoC Approach to Perinatal Affective Disorders: The Role of Neuroactive Steroids and Potential Threat
RDoC 治疗围产期情感障碍的方法:神经活性类固醇的作用和潜在威胁
基本信息
- 批准号:10595551
- 负责人:
- 金额:$ 4.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcousticsAcuteAddressAdverse effectsAffectAllopregnanoloneAnti-Anxiety AgentsAnxietyAnxiety DisordersBehavioralBiologicalBiological FactorsBiological MarkersComplexDataDevelopmentDiagnosisDiagnosticDisease remissionEtiologyFDA approvedFemaleFirst Pregnancy TrimesterGoalsHeterogeneityHormonalHormonesIndividualInfantInfant HealthKnowledgeLinkLongitudinal StudiesLow Birth Weight InfantLow incomeMaternal HealthMeasuresMediatingMental HealthMetabolismModelingMood DisordersMoodsMothersPathogenesisPatient Self-ReportPatientsPerinatalPeripheralPhenotypePhysiologicalPopulations at RiskPostmenopausePostpartum DepressionPostpartum PeriodPostpartum WomenPregnancyPregnancy TrimestersPregnanolonePregnant WomenPremature BirthProbabilityProgesteroneQuestionnairesRecording of previous eventsReportingReproductive EndocrinologyReproductive PhysiologyResearchResearch Domain CriteriaResearch PersonnelRiskRoleSecond Pregnancy TrimesterSerumSiteStartle ReactionStructure of terminal stria nuclei of preoptic regionSymptomsSystemThird Pregnancy TrimesterTrainingVariantWomanWorkanxiety symptomsassociated symptombiological adaptation to stresscomorbiditydepressive symptomsearly pregnancyexperienceimprovedindexingintravenous injectionminority patientmood symptomnegative moodneuralneural circuitneurosteroidspatient populationperinatal mental healthperinatal womenperipartum depressionpositive allosteric modulatorpremenstrual dysphoric disorderpreventprofiles in patientsreceptorreceptor sensitivityresponsetooltransmission processtrauma exposurewomen of color
项目摘要
PROJECT SUMMARY / ABSTRACT
Perinatal depression (PND) affects 6.5%-12.9% of mothers, with comorbid perinatal anxiety (PNA) occurring in
as many as 50% of cases. In low-income women of color, rates of these perinatal affective disorders (PNAD)
are even higher. PNAD are associated with adverse effects on both maternal and infant health and can contribute
to pre-term birth and low birth weight. It is important to further our understanding of PNAD to more efficaciously
identify and treat women, especially in at-risk populations. We must also address the considerable heterogeneity
of mental health symptoms and recognize the potential variations in pathogenesis and symptom profiles from
patient to patient. To our knowledge, despite this heterogeneity, studies to date have investigated biomarkers of
PNAD almost exclusively in relation to diagnoses rather than symptom phenotypes. The Research Domain
Criteria (RDoC) framework is a tool for applying new, multi-level mechanistic investigational approaches to
mental health, integrating self-report, behavioral, physiological and biological measures. RDoC tools have not
yet been applied to identify transdiagnostic phenotypes of PNAD and their neural basis. Neuroactive steroid
metabolites of progesterone fluctuate drastically during pregnancy and have been implicated in the pathogenesis
of PNAD. These neuroactive steroids alter the neural circuitry (i.e., inhibitory GABAA receptor) modulating certain
RDoC phenotypes, particularly potential threat, or responses to potentially aversive situations. Preliminary data
show potential threat to be an RDoC phenotype common in PNAD, and neuroactive steroids to relate to PNAD.
The next step is to link potential threat directly to neuroactive steroids, and to extend research to other
metabolites of progesterone, particularly early in pregnancy when rates of PNAD are highest in women of color.
The research goal of this proposal is to examine neuroactive steroid synthesis in relation to self-report and
physiological measures of potential threat as well as PNAD symptoms in early pregnancy in low-income women
of color. The specific aims are to (1) investigate acute increases in NAS synthesis as a mechanism of potential
threat in early pregnancy; (2) investigate the association of NAS synthesis with depression and anxiety
symptoms in early pregnancy, and whether potential threat mediates these associations; and (3) investigate the
acoustic startle response as a physiological index of potential threat and GABAA receptor sensitivity to NAS
during pregnancy. The training goals are to (1) develop a theoretical understanding of the RDoC framework
and apply the framework to the study of perinatal mental health phenotypes; (2) acquire training in processing
and analysis of neuroactive steroids, and gain knowledge of their association with PNAD; and (3) develop a
detailed understanding of female reproductive physiology and endocrinology, and relate this to perinatal affective
disorders. Ultimately, this training will allow the applicant to advance towards a goal of becoming an independent
academic researcher studying the pathogenesis and heterogeneity of perinatal mental health in low income,
minority patient populations.
项目摘要/摘要
围产期抑郁(PND)影响6.5%-12.9%的母亲,并伴有围产期焦虑(PNA)
多达50%的案例。在低收入有色人种妇女中,这些围产期情感障碍的发生率(PNAD)
甚至更高。PNAD与对孕产妇和婴儿健康的不利影响有关,并可能有助于
早产和低出生体重。重要的是要加深我们对PNAD的理解,以便更有效地
识别和治疗妇女,特别是在高危人群中。我们还必须解决相当大的异质性
并认识到在发病机制和症状特征方面的潜在差异
病人对病人。据我们所知,尽管存在这种异质性,但到目前为止,研究已经调查了
PNAD几乎完全与诊断有关,而不是症状表型。研究领域
标准(RDoC)框架是一种工具,用于将新的、多层次的机械性调查方法应用于
心理健康,综合自我报告、行为、生理和生物措施。RDoC工具尚未
目前已被应用于PNAD的跨诊断表型及其神经基础的鉴定。神经活性类固醇
孕酮代谢产物在妊娠期间波动剧烈,并与其发病机制有关。
Pnad的。这些神经活性类固醇改变神经回路(即抑制性GABAA受体),调节某些
RDoC表型,特别是潜在威胁,或对潜在厌恶情况的反应。初步数据
显示潜在的威胁是PNAD中常见的RDoC表型,以及与PNAD相关的神经活性类固醇。
下一步是将潜在威胁直接与神经活性类固醇联系起来,并将研究扩展到其他
孕酮的代谢物,特别是在怀孕早期,有色人种妇女的PNAD发生率最高。
这项建议的研究目标是检查神经活性类固醇合成与自我报告和
低收入妇女妊娠早期潜在威胁和PNAD症状的生理指标
一种颜色。其具体目的是(1)研究NAS合成的急剧增加作为潜在的
妊娠早期的威胁;(2)NAS合成与抑郁和焦虑的关系
怀孕早期的症状,以及潜在的威胁是否中介了这些联系;以及(3)调查
声惊厥反应作为潜在威胁和GABA受体对NAS敏感性的生理指标
在怀孕期间。培训目标是(1)从理论上理解RDoC框架
并将该框架应用于围产期心理健康表型的研究;(2)获得加工训练
和分析神经活性类固醇,并了解它们与PNAD的关联;以及(3)开发一种
详细了解女性生殖生理学和内分泌学,并将其与围产期情感联系起来
精神错乱。最终,这种培训将使申请者朝着成为独立人士的目标前进。
研究低收入人群围产期心理健康发病机制及异质性的学者,
少数族裔患者群体。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Elizabeth Wenzel其他文献
Elizabeth Wenzel的其他文献
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{{ truncateString('Elizabeth Wenzel', 18)}}的其他基金
An RDoC Approach to Perinatal Affective Disorders: The Role of Neuroactive Steroids and Potential Threat
RDoC 治疗围产期情感障碍的方法:神经活性类固醇的作用和潜在威胁
- 批准号:
10464233 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
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