The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression

炎症和谷氨酸能过程在青少年抑郁症神经发育机制中的作用

基本信息

项目摘要

PROJECT SUMMARY First episodes of major depressive disorder (MDD) typically begin during adolescence. Despite the fact that adolescent-onset MDD is associated with more severe and recurrent episodes of MDD, little work has been done to identify mechanisms underlying depressive relapse or recurrence. Prior work by the candidate has documented differences in functional and structural connectivity involving the anterior cingulate cortex (ACC) between adolescents with MDD and psychiatrically healthy controls; these phenotypes are posited to reflect altered neurodevelopment in key emotion regulation circuitry. We do not yet know, however, whether and how MDD impacts adolescent development of ACC connectivity in a manner that contributes to an increased risk of depressive relapse or recurrence. One mechanism may be the immune system, which activates in response to psychosocial stressors and influences neurotransmitter systems including glutamate, the primary excitatory neurotransmitter in the brain. Basic research indicates that higher levels of pro-inflammatory cytokines leads to overexcitation of glutamatergic neurons to the point of neurotoxicity and, consequently, to reduced neuroplasticity. Further, neuroimaging studies of adult MDD have reported heightened levels of inflammation and altered levels of glutamate in the ACC. These data, combined with growing evidence that ACC connectivity undergoes extensive maturation during adolescence, suggest that heightened inflammation and excessive glutamate may lead to atypical development of this circuitry in adolescents with MDD. The candidate therefore seeks to test the central hypothesis that heightened inflammation acts through glutamate transmission to disrupt typical neurodevelopment of ACC connectivity in adolescents with MDD to increase risk of depressive relapse or recurrence. This K01 will test this model in 60 adolescents with first episodes of MDD assessed longitudinally over 3 time points using an innovative multimodal approach. The candidate will assay peripheral levels of pro-inflammatory cytokines using dried blood spot technology, noninvasively image glutamate and antioxidants in ACC using proton magnetic resonance spectroscopy, and assess neurodevelopmental changes of ACC connectivity using functional (resting-state fMRI) and structural (diffusion MRI) methods. This K01 fills key gaps in our understanding of whether adolescent MDD impacts development of ACC connectivity, how inflammatory and glutamatergic mechanisms underlying MDD-related changes in ACC connectivity contribute to subsequent relapse or recurrence in adolescents with MDD, and whether antioxidants protect against depression recurrence by buffering the effects of inflammation on adolescent development of ACC circuitry. Importantly, the candidate will execute this research in the context of receiving advanced training in stress-related immune biology, causal inference modeling, and developmental psychopathology. Results from this project will culminate in an R01 that aims to identify subtypes/biotypes of adolescent MDD based on clinical course and multimodal characterizations of brain trajectories.
项目总结

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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TIFFANY CHEING HO其他文献

TIFFANY CHEING HO的其他文献

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{{ truncateString('TIFFANY CHEING HO', 18)}}的其他基金

Integrating 1H MRS with 2H-Labeled Glucose to Characterize Dynamic Glutamate Metabolism in Major Depressive Disorder
将 1H MRS 与 2H 标记的葡萄糖相结合来表征重度抑郁症的动态谷氨酸代谢
  • 批准号:
    10668075
  • 财政年份:
    2023
  • 资助金额:
    $ 5.66万
  • 项目类别:
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents with Depression: Toward Predictors of Treatment Response and Clinical Course
抑郁症青少年持续威胁的炎症和谷氨酸机制:治疗反应和临床过程的预测因子
  • 批准号:
    10755122
  • 财政年份:
    2022
  • 资助金额:
    $ 5.66万
  • 项目类别:
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents with Depression: Toward Predictors of Treatment Response and Clinical Course
抑郁症青少年持续威胁的炎症和谷氨酸机制:治疗反应和临床过程的预测因子
  • 批准号:
    10622580
  • 财政年份:
    2022
  • 资助金额:
    $ 5.66万
  • 项目类别:
Inflammatory and Glutamatergic Mechanisms of Sustained Threat in Adolescents with Depression: Toward Predictors of Treatment Response and Clinical Course
抑郁症青少年持续威胁的炎症和谷氨酸机制:治疗反应和临床过程的预测因素
  • 批准号:
    10445166
  • 财政年份:
    2022
  • 资助金额:
    $ 5.66万
  • 项目类别:
The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression
炎症和谷氨酸能过程在青少年抑郁症神经发育机制中的作用
  • 批准号:
    10756332
  • 财政年份:
    2018
  • 资助金额:
    $ 5.66万
  • 项目类别:
The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression
炎症和谷氨酸能过程在青少年抑郁症神经发育机制中的作用
  • 批准号:
    10551423
  • 财政年份:
    2018
  • 资助金额:
    $ 5.66万
  • 项目类别:
The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression
炎症和谷氨酸能过程在青少年抑郁症神经发育机制中的作用
  • 批准号:
    9933235
  • 财政年份:
    2018
  • 资助金额:
    $ 5.66万
  • 项目类别:
The Roles of Inflammatory and Glutamatergic Processes in the Neurodevelopmental Mechanisms Underlying Adolescent Depression
炎症和谷氨酸能过程在青少年抑郁症神经发育机制中的作用
  • 批准号:
    10165829
  • 财政年份:
    2018
  • 资助金额:
    $ 5.66万
  • 项目类别:

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REU Site: Equitable Data Science in Adolescent Development
REU 网站:青少年发展中的公平数据科学
  • 批准号:
    2243973
  • 财政年份:
    2023
  • 资助金额:
    $ 5.66万
  • 项目类别:
    Continuing Grant
Collaborative Research: Adolescent Development, Legal Comprehension, and Decision-Making Among Justice-Involved Youth
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    2146965
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    2022
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    $ 5.66万
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Characterising the nature of mental health trajectories across adolescent development through the integration of genomic, biomarker, neuroimaging and
通过整合基因组、生物标志物、神经影像学和
  • 批准号:
    2744399
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    2022
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    $ 5.66万
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Collaborative Research: Adolescent Development, Legal Comprehension, and Decision-Making Among Justice-Involved Youth
合作研究:青少年发展、法律理解和参​​与司法的青少年的决策
  • 批准号:
    2146686
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Behavioral and neural mechanisms of reward responsivity across normative and at-risk adolescent development
规范和高危青少年发展中奖励反应的行为和神经机制
  • 批准号:
    10705724
  • 财政年份:
    2021
  • 资助金额:
    $ 5.66万
  • 项目类别:
Behavioral and neural mechanisms of reward responsivity across normative and at-risk adolescent development
规范和高危青少年发展中奖励反应的行为和神经机制
  • 批准号:
    10387432
  • 财政年份:
    2021
  • 资助金额:
    $ 5.66万
  • 项目类别:
Behavioral and neural mechanisms of reward responsivity across normative and at-risk adolescent development
规范和高危青少年发展中奖励反应的行为和神经机制
  • 批准号:
    10526284
  • 财政年份:
    2021
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    $ 5.66万
  • 项目类别:
Parental behavior, human-animal interaction, and adolescent development
父母行为、人与动物互动和青少年发展
  • 批准号:
    10213794
  • 财政年份:
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    $ 5.66万
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  • 批准号:
    9759338
  • 财政年份:
    2019
  • 资助金额:
    $ 5.66万
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Emergence of Implicit Bias during Adolescent Development
青少年发展过程中隐性偏见的出现
  • 批准号:
    10541760
  • 财政年份:
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  • 资助金额:
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