2/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
晚年抑郁症中的 2/2-多巴胺能障碍(D3 研究)
基本信息
- 批准号:10426325
- 负责人:
- 金额:$ 88.19万
- 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:2020-09-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:Academic Medical CentersAddressAgeAgingBehaviorBehavior assessmentBehavioralBehavioral SymptomsBindingBrainClinicalClinical assessmentsCognitionCognitiveCognitive deficitsCorpus striatum structureCrossover DesignDataData SetDecision MakingDepressed moodDepressive SyndromesDevelopmentDopamineDopamine D2 ReceptorDopamine ReceptorElderlyEnrollmentEvaluationExecutive DysfunctionExhibitsExpenditureFunctional Magnetic Resonance ImagingFunctional disorderFutureGaitGait speedGenderGoalsImpairmentInflammatoryInstitutesInterventionLeadLevodopaMagnetic Resonance ImagingMeasurementMeasuresMental DepressionMidbrain structureModelingMolecularMoodsMotivationMotorMovementNeurocognitiveNeuropsychologyNew YorkOutcomeOutpatientsParticipantPathway interactionsPatient Self-ReportPerformancePharmacologyPhasePhenotypePhysical FunctionPhysical PerformancePlacebosPositive ValencePositron-Emission TomographyPrefrontal CortexProcessPublishingRandomizedResearchResearch Domain CriteriaRewardsSignal TransductionSiteStructureSubstantia nigra structureSystemTestingTimeUniversitiesWorkage effectage relatedbasebehavior measurementcerebral atrophycognitive systemcognitive testingcostdopamine systemdopamine transportergeriatric depressionhedonicimprovedinflammatory markerinnovationmiddle agemultimodalityneurochemistryneuromelaninnew therapeutic targetnormal agingnovelpars compactapersonalized medicineprocessing speedreceptor densityrelating to nervous systemresponsereward processingsensorimotor systemtherapy developmenttransmission processwillingnessyoung adult
项目摘要
PROJECT SUMMARY: Growing evidence suggests that dopamine contributes to key functions in multiple
RDoC domains, specifically Positive Valence Systems, Cognitive Systems, and Sensorimotor Systems. In
Late-Life Depression (LLD), dysfunction in all these systems is common, portends poor outcomes, and
manifests as deficits in motivation and effort, executive dysfunction, and gait impairment. While studies of
dopamine function in early and midlife depression primarily focus on reward processing, they often exclude the
cognitive and sensorimotor domains relevant for older adults despite a recognized decline in dopamine
function with normal aging. The objectives of this collaborative R01 proposal between Columbia
University/New York State Psychiatric Institute and Vanderbilt University Medical Center are to: 1) characterize
dopaminergic dysfunction in LLD across multiple RDoC domains (Positive Valence Systems, Cognitive
Systems, and Sensorimotor Systems) at several levels of analysis (cellular [PET], circuit [MRI], and behavioral
/ self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to stimulation with
levodopa (L-DOPA). Supported by pilot data, this project builds on our past work demonstrating that
dopamine function declines with aging, that dopaminergic dysfunction contributes to deficits in behavioral
measures of the Positive Valence Systems, Cognitive Systems, and Sensorimotor Systems, and that L-DOPA
administration improves performance in these systems. The long-term goal of this line of research is to
determine how dopaminergic dysfunction contributes to clinical presentations of LLD, how responsive
behavioral symptoms are to modulation of dopamine function, and to identify novel targets for future
interventions. Our approach is to enroll 60 psychiatrically healthy elders (30 per site) and 120 depressed
elders (60 per site) exhibiting likely dopaminergic dysfunction, characterized as either slowed processing
speed or slowed gait speed. Participants will undergo thorough clinical characterization and complete PET
imaging measuring dopamine synthesis and dopamine receptor availability, neuromelanin-sensitive MRI
measurement of long-term nigrostriatal dopamine transmission, task positive MRI focused on effort-based
decision making and reward processing, a comprehensive neurocognitive evaluation, a physical performance
evaluation, and measurement of inflammatory markers. To assess responsivity of the dopamine system to
modulation, depressed subjects then will be randomized to L-DOPA or placebo for 3 weeks, followed by repeat
multimodal MRI and cognitive/behavioral assessments. Using a cross-over design, participants will receive the
opposite intervention for an additional 3 weeks followed by clinical and cognitive assessments only. This
proposal is significant and innovative, as no prior published study has comprehensively examined
dopamine-dependent behaviors in LLD. This will inform treatment approaches focusing on facilitating cognition
and movement, reducing the effort cost of voluntary behavior, and promoting behavioral activation.
项目总结:越来越多的证据表明,多巴胺在多个方面发挥着关键作用
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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Warren D Taylor其他文献
A Systematic Review of Antidepressant Placebo-Controlled Trials for Geriatric Depression: Limitations of Current Data and Directions for the Future
老年抑郁症抗抑郁药安慰剂对照试验的系统评价:当前数据的局限性和未来的方向
- DOI:
10.1038/sj.npp.1300550 - 发表时间:
2004-09-01 - 期刊:
- 影响因子:7.100
- 作者:
Warren D Taylor;P Murali Doraiswamy - 通讯作者:
P Murali Doraiswamy
Translational Research in Late-Life Mood Disorders: Implications for Future Intervention and Prevention Research
晚年情绪障碍的转化研究:对未来干预和预防研究的启示
- DOI:
10.1038/sj.npp.1301333 - 发表时间:
2007-02-28 - 期刊:
- 影响因子:7.100
- 作者:
Gwenn S Smith;Faith M Gunning-Dixon;Francis E Lotrich;Warren D Taylor;Jovier D Evans - 通讯作者:
Jovier D Evans
MECHANISMS INFORMING INTERVENTIONS: NEW APPROACHES TO TREATING LATE-LIFE DEPRESSION: Session 107
- DOI:
10.1016/j.jagp.2019.01.144 - 发表时间:
2019-03-01 - 期刊:
- 影响因子:
- 作者:
Eric Lenze;Faith Gunning;Jordan F Karp;Warren D Taylor - 通讯作者:
Warren D Taylor
Warren D Taylor的其他文献
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{{ truncateString('Warren D Taylor', 18)}}的其他基金
2/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
晚年抑郁症中的 2/2-多巴胺能障碍(D3 研究)
- 批准号:
10249325 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
Nicotinic Modulation of the Cognitive Control System in Late-Life Depression
晚年抑郁症认知控制系统的烟碱调节
- 批准号:
10495486 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
Expansion of the Dopaminergic Dysfunction in Late-Life Depression Study (The D3 Study)
晚年抑郁症中多巴胺能障碍研究的扩展(D3 研究)
- 批准号:
10793937 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
Nicotinic Modulation of the Cognitive Control System in Late-Life Depression
晚年抑郁症认知控制系统的烟碱调节
- 批准号:
10225310 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
1/3-Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-life Depression (Rembrandt)
晚年抑郁症的 1/3 复发标记、认知负担和神经生物学稳态(伦勃朗)
- 批准号:
10304154 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
2/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
晚年抑郁症中的 2/2-多巴胺能障碍(D3 研究)
- 批准号:
10640269 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
2/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)
晚年抑郁症中的 2/2-多巴胺能障碍(D3 研究)
- 批准号:
10029130 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
1/3-Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-life Depression (Rembrandt)
晚年抑郁症的 1/3 复发标记、认知负担和神经生物学稳态(伦勃朗)
- 批准号:
10523127 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
1/3-Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-life Depression (Rembrandt)
晚年抑郁症的 1/3 复发标记、认知负担和神经生物学稳态(伦勃朗)
- 批准号:
10118837 - 财政年份:2020
- 资助金额:
$ 88.19万 - 项目类别:
Mentoring and Research on Neurobiological Markers of Clinical Outcomes in Depression
抑郁症临床结果神经生物学标志物的指导和研究
- 批准号:
9343063 - 财政年份:2016
- 资助金额:
$ 88.19万 - 项目类别:
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