Biomarkers in the HPA axis and inflammatory pathways for maladaptive stress response in children
HPA 轴的生物标志物和儿童适应不良应激反应的炎症通路
基本信息
- 批准号:9475313
- 负责人:
- 金额:$ 65.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-04-21 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAgeAttenuatedBehavioralBiologicalBiological MarkersC-reactive proteinCessation of lifeChildChildhoodChronicChronic DiseaseChronic stressClinical DataComorbidityDevelopmentDiagnosisDiseaseFamilyFeasibility StudiesFeeling suicidalGene ExpressionGenesGlucocorticoid ReceptorGoalsHairHydrocortisoneHyperactive behaviorImmune responseIncidenceInflammationInflammatoryIntakeInterleukin-1 betaLongitudinal StudiesMalignant NeoplasmsMeasuresMental DepressionMental disordersNeurobiologyNeurosecretory SystemsNewly DiagnosedParent-Child RelationsParentsPathway interactionsPatternPopulationPost-Traumatic Stress DisordersPreventive InterventionPsychopathologyPubertyQuality of lifeRecording of previous eventsResearch InfrastructureRiskSalivarySiblingsSignal TransductionStressSuicideTNF geneTarget PopulationsTimeagedbiological adaptation to stressbiological systemscancer diagnosiscytokinehigh riskhypothalamic-pituitary-adrenal axisinflammatory markernovelprotective factorsreceptor sensitivityrecruitresponseresponse biomarkersexstressorsuicidal patientsuicidal risksymptomatology
项目摘要
Activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress. However, when
repeatedly activated, HPA axis dysregulation can result. Stress in childhood alters biological systems and the
expression of genes regulating HPA axis and immune responses in a manner that persists across decades.
Stress is also associated with increased risk for depression and PTSD, a risk that continues into adulthood,
and both are associated with increased risk for suicidality. However different neuroendocrine profiles are
described with increased cortisol and reduced glucocorticoid receptor (GR) responsiveness in depression; and
attenuated cortisol and enhanced GR responsiveness in PTSD. Inflammation, also associated with stress, is
believed to result from reduced GR sensitivity, possibly as a result of chronically elevated cortisol. Yet
inflammation is associated with both depression and PTSD, which is difficult to rectify with their apparently
differential pattern of GR responsiveness. The discrepant HPA axis profiles also do not conform with the high
comorbidity rate between these disorders. Our overarching goal is to examine the trajectories of the HPA axis
and inflammatory pathways in response to stress in children; and identify biological trajectories that predict
maladaptive stress responses. We propose to recruit 200 children, aged 12-17 years, of parents newly
diagnosed with advanced stage cancer (stress) within 3 months of diagnosis (intake) and follow them at 6 and
18 months following intake. This population will allow us to study the unfolding of stress responses, which is
almost impossible to capture for other stressors. We will also recruit and follow 100 children from families
where a parent or siblings do not have cancer or chronic illness or death (controls). We propose to measure
gene expression in the HPA axis and inflammatory pathways; hair cortisol concentrations (HCC) to measure
chronic HPA axis activity; salivary cortisol to measure cortisol awakening response (CAR); GR sensitivity; C-
Reactive Protein and inflammatory cytokines; and collect clinical data. We hypothesize that within 3 months of
parental diagnosis, stress children will show increased expression of HPA axis and inflammatory genes and
increased HCC, CAR, and inflammatory markers compared to controls; but no differences in GR sensitivity. In
response to chronic stress, stress children will show decreased expression of HPA axis genes, enhanced GR
sensitivity, and decreased HCC and CAR over time compared to controls. They will also continue to show
increased expression of inflammatory genes and inflammation. Biological responses early on and their
trajectories will predict symptomatology (depression, PTSD, and suicidal ideation) and onset of depression and
PTSD; and these relationships will be influenced by pre-existing and ongoing vulnerability and protective
factors. This study will advance our understanding of the neurobiological, environmental, and behavioral
pathways of stress responses in children and its impact on liability to psychiatric illness. It will also result in
biomarkers that signal risk in children early on and can be targeted by early preventions and interventions.
下丘脑-垂体-肾上腺(HPA)轴的激活是对压力的适应性反应。然而,当
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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Nadine M. Melhem其他文献
11.2 PLACENTAL INFLAMMATION AND ITS ASSOCIATION WITH CHILDHOOD MENTAL DISEASE
- DOI:
10.1016/j.jaac.2020.08.166 - 发表时间:
2020-10-01 - 期刊:
- 影响因子:
- 作者:
Blake A. Gibson;Nadine M. Melhem - 通讯作者:
Nadine M. Melhem
Nadine M. Melhem的其他文献
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{{ truncateString('Nadine M. Melhem', 18)}}的其他基金
COVID-19, Inflammation and HPA axis activity, and Risk for Psychopathology in Youth
COVID-19、炎症和 HPA 轴活动以及青少年精神病理学风险
- 批准号:
10753189 - 财政年份:2023
- 资助金额:
$ 65.13万 - 项目类别:
Biological Substrates of Maladaptive Stress Response in Early Childhood
幼儿期适应不良应激反应的生物基础
- 批准号:
10406368 - 财政年份:2020
- 资助金额:
$ 65.13万 - 项目类别:
Biological Substrates of Maladaptive Stress Response in Early Childhood
幼儿期适应不良应激反应的生物基础
- 批准号:
10250530 - 财政年份:2020
- 资助金额:
$ 65.13万 - 项目类别:
Biological Substrates of Maladaptive Stress Response in Early Childhood
幼儿期适应不良应激反应的生物基础
- 批准号:
10885448 - 财政年份:2020
- 资助金额:
$ 65.13万 - 项目类别:
Biological Substrates of Maladaptive Stress Response in Early Childhood
幼儿期适应不良应激反应的生物基础
- 批准号:
10661926 - 财政年份:2020
- 资助金额:
$ 65.13万 - 项目类别:
Biological Substrates of Maladaptive Stress Response in Early Childhood
幼儿期适应不良应激反应的生物基础
- 批准号:
10626021 - 财政年份:2020
- 资助金额:
$ 65.13万 - 项目类别:
Prevention and Assessment of Risk in Teens (PART) Longitudinal Study
青少年风险预防和评估(PART)纵向研究
- 批准号:
10631226 - 财政年份:2018
- 资助金额:
$ 65.13万 - 项目类别:
Prevention and Assessment of Risk in Teens (PART) Longitudinal Study
青少年风险预防和评估(PART)纵向研究
- 批准号:
10435006 - 财政年份:2018
- 资助金额:
$ 65.13万 - 项目类别:
Biomarkers in the HPA axis and inflammatory pathways for maladaptive stress response in children
HPA 轴的生物标志物和儿童适应不良应激反应的炎症通路
- 批准号:
9896866 - 财政年份:2017
- 资助金额:
$ 65.13万 - 项目类别:
Identifying Predictors in the HPA Axis and Inflammatory Pathways for Suicidal Behavior in Youth
确定 HPA 轴和炎症通路中青少年自杀行为的预测因素
- 批准号:
9234320 - 财政年份:2017
- 资助金额:
$ 65.13万 - 项目类别:
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