Primary Reward Mechanism Dysfunction if Depression

抑郁时主要奖励机制功能障碍

• 批准号: 7665321
• 负责人: JOSE MATHEWS
• 金额: $ 17.02万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7665321
• 关键词: Address; Amygdaloid structure; Anhedonia; Anterior; Aversive Stimulus; Award; Biology; Brain region; Corpus striatum structure; DSM-IV; Desire for food; Diagnosis; Diagnostic; Eating; Education; Emotional; Epidemiologic Studies; Event; Fruit; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Heterogeneity; Human; Image; Juice; K-Series Research Career Programs; Lateral; Light; Major Depressive Disorder; Medial; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Metric; Modality; Motivation; Participant; Patients; Prefrontal Cortex; Prevalence; Process; Public Health; Quinine; Recruitment Activity; Research; Research Personnel; Research Project Grants; Rewards; Role; Scientist; Severities; Stimulus; Structure; Symptoms; System; Taste Perception; Testing; Time; Training Support; Translational Research; Ventral Striatum; Visual; abstracting; cingulate cortex; depressed; depression; effective intervention; expectation; interest; neural circuit; neuroimaging; pleasure; programs; relating to nervous system; research study; response; reward circuitry; reward processing; skills; therapeutic target

DESCRIPTION (provided by applicant): This proposed Mentored Patient-Oriented Research Career Development Award (K-23) research project will provide me the support and training to become a successful independent researcher. The research plan studies participants with Major Depressive Disorder (MOD), a common and devastating mental illness. Specifically, the research probes the functioning of the primary reward system in depression as it can shed light on the core symptom of anhedonia that can provide important future therapeutic target for more effective interventions. Taste stimuli in the form of fruit juice (pleasant) and quinine (aversive) will be delivered during event-related fMRI to characterize the reward circuitry and it's functioning in un-medicated depressed patients by contrasting it with normal controls. Also, possible differential response to taste reward versus monetary reward will be investigated in the exploratory aim. We will recruit 40 participants with MOD and 40 matched controls to test our hypothesis. We hypothesize that compared to controls, during the anticipation of the pleasant taste; depressed patients will have decreased activation in the ventral striatum with relatively preserved or minimal dysfunction in the activation in the orbitofrontal cortex (OFC) to the receipt of the pleasant taste (specific aim 1). Furthermore, depressed patients will have greater activation to the anticipation of the aversive stimuli (quinine) in the amygdala with minimally increased or preserved representaion of receipt in the anterior cingulate cortex and the OFC (more lateral to the reward activations) [specific aim 2]. We will then use a dual reward paradigm with both taste and monitory reward in the same experiment simultaneously. We hypothesize that the anticipation of monetary reward will elicit a larger activation in the ventral striatum and the representation of the receipt of monetary reward will be more anteriorly situated in the OFC when compared to primary taste reward. (Exploratory aim) In patients with depression, the anticipatory component of primary reward will be more compromised than the anticipation of money whereas in the receipt component, the response to juice will be preserved while the receipt of money will be compromised. This mentored career development award will provide me the essential time; education and mentoring to develop my research skills by conducting the translational research detailed in the award thus accomplish my goal of becoming an independent scientist.

描述（由申请人提供）：这项拟议的指导的面向患者的研究职业发展奖（K-23）研究项目将为我提供支持和培训，以成为成功的独立研究人员。研究计划研究参与者患有严重抑郁症（MOD），这是一种常见且毁灭性的精神疾病。具体而言，该研究探究了抑郁症中主要奖励系统的功能，因为它可以阐明Anhedonia的核心症状，这些核心症状可以为更有效的干预提供重要的未来治疗靶标。在与事件相关的fMRI期间，将以果汁（宜人）和奎宁（厌恶）形式的口味刺激，以表征奖励电路，并通过将其与正常对照组对比，在未经药物的抑郁症患者中起作用。同样，将在探索目标中研究对品味奖励与货币奖励的可能差异反应。我们将招募40名具有MOD和40个匹配对照的参与者来检验我们的假设。我们假设与对照组相比，期待宜人的味道。抑郁症患者将在腹侧纹状体中降低活化，而轨道额皮层（OFC）的激活相对保留或最小功能障碍，以收到愉悦的味道（特定的AIM 1）。此外，抑郁症患者将在杏仁核中对厌恶刺激（奎宁）的预期更大，而在前扣带回皮层和OFC中的收据表示最小或保留的代表（奖励激活的侧面更侧面）[特定目标2]。然后，我们将同时在同一实验中使用双重奖励范式，并同时具有口味和Montority奖励。我们假设对货币奖励的预期将引起腹侧纹状体的更大激活，并且与主要的口味奖励相比，OFC的收到货币奖励的代表将更加前方位于OFC中。 （探索目的）在抑郁症患者中，主要奖励的预期成分将比预期货币的预期更加妥协，而在收据部分中，将保留对果汁的反应，而收到货币的收据将被妥协。这个指导的职业发展奖将为我提供必要的时间。教育和指导通过进行奖项中详细介绍的翻译研究来发展我的研究技能，从而实现了我成为独立科学家的目标。