Cognitive, Clinical and Neural Markers of Late Life Depression

晚年抑郁症的认知、临床和神经标志物

• 批准号: 8204078
• 负责人: Sara L. Weisenbach
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204078
• 关键词: Acetylcholinesterase Inhibitors; Adult; Age; Anterior; Antidepressive Agents; Area; Attention; Award; Behavior Therapy; Behavior assessment; Behavioral; Brain region; Caregivers; Caring; Clinic; Clinical; Cognition; Cognitive; Comorbidity; Complex; Control Groups; Corpus striatum structure; Data; Development; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Etiology; Evaluation; Evolution; Family; Family Caregiver; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Gender; Goals; Impaired cognition; Impairment; Individual; Investigation; Knowledge; Laboratories; Lead; Leadership; Life; Link; Maps; Measures; Mediating; Medical Education; Mental Depression; Monitor; Neurobiology; Nucleus Accumbens; Outcome; Participant; Pathology; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Phenotype; Physicians; Prevalence; Prevention strategy; Productivity; Psychotherapy; Reading; Recommendation; Regimen; Relative (related person); Research; Research Personnel; Research Project Grants; Resistance; Rest; Sampling; Scanning; Seeds; Signal Transduction; Site; Symptoms; Techniques; Time; Training; Translating; Treatment Protocols; Veterans; Visit; Work; behavior measurement; behavior rating scale; career; clinical care; clinically significant; cognitive neuroscience; cost; design; efficacy testing; endophenotype; executive function; follow-up; functional decline; geriatric depression; improved; instrument; interest; knowledge base; meetings; neural circuit; neuroimaging; neuropsychological; outcome forecast; problem solving therapy; prophylactic; relating to nervous system; selective attention; skills; standard of care; tool; translational neuroscience; treatment response; treatment strategy

DESCRIPTION (provided by applicant) The applicant is a clinical neuropsychologist whose long-term career goal is to become an independent researcher conducting work in the translational neuroscience of late life depression (LLD) using neuropsychological and neuroimaging tools. Individuals with LLD are thought to encompass a neurobiologically heterogeneous group. Previous studies with small samples and mixed etiologies of LLD subjects have been limited in their development of knowledge of the basis of the disorder and of sub-phenotypes, but have been important in taking first steps toward difficult goals. For example, individuals with LLD present with high rates of treatment resistance to typical antidepressant regimens, increased vulnerability to decline in cognition and function, and high rates of treatment non-adherence. Some initial efforts have been made to identify more accurate intermediate endophenotypes (IE) of individuals with LLD, which might improve prediction of who is most likely to display cognitive and functional decline and identify individuals most likely to respond to specific treatment regimens. To date, research on LLD has focused primary on executive functioning deficits, related to disruption of dorsolateral-striatal circuitry using small samples. Observations of executive functioning deficits and associated disruption to dorsolateral-striatal pathways among patients with LLD have been predictive of poor psychiatric outcomes, such as treatment resistance. In addition, there has been less investigation into the ability of baseline neuropsychological and neuroimaging measures to predict the course of broad cognitive and functional decline, despite the fact that prediction is precisely what clinicians and families might find most useful in planning and care. Furthermore, clinical measures such as apathy and the potential predictive validity of such measures in related neural circuitry, is as yet unknown. Establishing which neuropsychological and clinical measures are related to the neural circuitry underlying LLD can be of signal value toward developing treatment to protect and enhance the respective underlying neural circuits. Furthermore, if these measures and circuits are predictive of course and change in broad cognitive areas, clinical features, and everyday functioning, this knowledge could more readily be transferred to clinical care practices. Thus, the primary objective of this study is to probe two neural circuits implicated in the etiology of LLD. To achieve this objective, the candidate proposes to distinguish neural circuitry related to executive dysfunction (as defined by comprehensive baseline neuropsychological assessment) from circuitry related to symptoms of apathy using resting state functioning connectivity (rRSfC, a functional MRI technique that examines neural connectivity of brain regions during a resting state), as well as diffusion tensor imaging as a microstructural compliment. Furthermore, the project is designed as a longitudinal, predictive study. It uses neuropsychological, clinical, and neural circuitry measures to map and predict course of LLD, including changes in cognitive areas, clinical features, and everyday functioning. It is designed so that cognitive and behavioral features of LLD that predict decline can be effectively evaluated and easily translated into clinic settings. Participants will include 40 individuals with LLD, antidepressant-free at baseline, relative to 20 controls. The two groups will be matched for age, gender, education, and medical comorbidities. They will be re-assessed at one- and two-year follow-up visits with a neuropsychological battery, including symptom and behavioral measures, to better understand the extent to which baseline neuropsychological alterations can predict the course of cognition and function among individuals with LLD. Linking neurobiological circuitry with neuropsychological and behavioral measures will allow for the mechanistic definition of simplified, non-imaging measures, anchored on a background of neurobiological correlates that may predict the course of cognition and function of LLD, leading to more accurate assessments, the specification of more valid phenotypes in this complex illness, and a better targeting of preventive and treatment strategies.

描述（由申请人提供） 申请人是一名临床神经心理学家，其长期职业目标是成为一名独立的研究人员，使用神经心理学和神经影像学工具从事后期生活抑郁症（LLD）转化神经科学的工作。患有LLD的个体被认为包括神经生物学上异质的群体。 先前针对LLD主题的小样本和混合病因的研究在开发有关该疾病基础和子表型的知识方面受到限制，但对于朝着艰难目标迈出的第一步非常重要。 例如，患有LLD的个体具有较高的治疗率对典型抗抑郁方案的耐药性，认知和功能下降的脆弱性增加，并且不遵守治疗率很高。已经采取了一些初步的努力来确定LLD患者更准确的中间型内表型（IE），这可能会改善对谁最有可能表现出认知和功能下降的预测，并确定最有可能对特定治疗方案做出反应的人。迄今为止，对LLD的研究主要集中在执行功能缺陷上，这与使用小样本的背外侧 - 纹状体电路中断有关。 LLD患者对执行功能缺陷的观察以及与背外侧纹状体途径相关的破坏已经预测了精神病性不佳，例如治疗耐药性。 此外，尽管预测恰恰是临床医生和家庭可能在计划和护理中最有用的，但对基线神经心理学和神经影像措施的能力进行了更少的研究。 此外，相关神经回路中这种措施等临床指标（例如冷漠和此类措施的潜在预测有效性）尚不清楚。确定哪些神经心理学和临床措施与LLD的神经回路有关，可以具有信号价值，以开发治疗以保护和增强各自的潜在神经回路。此外，如果这些措施和电路在广泛的认知领域，临床特征和日常功能方面具有预测性，并且这些知识可以更容易地转移到临床护理实践中。 因此，这项研究的主要目的是探测与LLD病因有关的两个神经回路。 为了实现这一目标，候选人提议区分与执行功能障碍（由全面的基线神经心理评估定义）与使用静息状态功能连接（RRSFC，功能性MRI技术）相关的电路相关的神经回路（由全面的基线神经心理评估定义），该电路是一种功能性MRI技术，可在静息状态下检查脑部元素的神经连接性。此外，该项目被设计为一项纵向，预测性研究。 它使用神经心理学，临床和神经回路测量来绘制和预测LLD的过程，包括认知领域的变化，临床特征和日常功能。它的设计使得可以有效评估并容易转化为临床环境的LLD的认知和行为特征。 相对于20个对照组，参与者将包括40名LLD，基线时无抗抑郁药的人。 这两个小组将与年龄，性别，教育和医学合并症相匹配。 他们将通过神经心理学电池（包括症状和行为措施）进行一年和两年的随访，以更好地了解基线神经心理学改变可以预测LLD患者认知和功能的进程。将神经生物学电路与神经心理学和行为措施联系起来，将允许对简化，非成像措施的机械定义，锚定在神经生物学相关的背景下，这些相关性可能预测了LLD的认知和功能过程，从而导致更准确的评估，对这种复杂的疾病的规格进行了更为有效的疾病的规范，并具有更好的治疗方法，并具有更好的治疗策略和一种更好的目标策略。