Toward understanding dopamine receptor contributions to prediction error and reversal learning in anorexia nervosa
了解多巴胺受体对神经性厌食症预测误差和逆转学习的贡献
基本信息
- 批准号:9805065
- 负责人:
- 金额:$ 23.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2021-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdolescentAdultAgonistAmerican Psychiatric AssociationAmisulprideAnorexia NervosaAvoidance LearningBehavioralBiological MarkersBody Weight decreasedBrainBrain imagingBromocriptineClinical ResearchCodeControl GroupsCorpus striatum structureDataDevelopmentDiseaseDopamineDopamine D1 ReceptorDopamine D2 ReceptorDopamine ReceptorEatingEating DisordersExploratory/Developmental GrantFoodFoundationsFrightFunctional disorderFunding MechanismsFutureHumanImpairmentIndividualInsula of ReilInterventionInvestigationMagnetic ResonanceMental disordersNeurotransmitter ReceptorNeurotransmittersPathway interactionsPharmaceutical PreparationsPharmacological TreatmentPharmacologyPhasePlacebosPopulationProtocols documentationRelapseResearchResearch DesignReversal LearningRewardsRoleSerotoninSignal TransductionStimulusTaste PerceptionTestingVentral StriatumWeight GainWomanaripiprazolebehavioral responsebrain behaviordopamine systemdopaminergic neuroneffective therapyfood restrictionfrontal lobeimprovedlearned behaviormortalityneuroimagingpsychologicreceptorresponsereward circuitryreward processing
项目摘要
Project Summary/Abstract
Anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and
severe weight loss. AN has the highest mortality rate among the psychiatric disorders; however, little is known
about biomarkers, and no medication has been approved for AN. Many individuals only partially recover, and
treatment options, especially for the psychological components of the illness, are not very effective, highlighting
the need for more effective treatments.
Brain reward pathways have a direct impact on the drive to eat, and a variety of neuroimaging studies have
suggested altered reward processing in AN. The neurotransmitter dopamine has a central role in the reward
circuitry to drive food approach, and the dynamic interplay between dopamine receptor response and food
restriction could have implications for the pathophysiology of AN. Dopamine-related brain function has been
studied indirectly using functional magnetic resonance brain imaging (fMRI) and tasks that deliver reward
stimuli unexpectedly, eliciting the so-called prediction error (PE) response. Research in AN showed repeatedly
altered PE processing suggesting altered dopamine circuit function in the disorder. Dopamine and PE
response have also been associated with altered reversal learning, which has important treatment implication
for AN as reversal learning is impaired in the disorder and modulation of the dopamine system could improve
treatment. However, the dopamine receptor mechanisms that underlie altered PE response in AN have not
been studied. This could be highly important to develop medication interventions.
In this application, we will develop a study protocol and gather pilot data to identify whether specific
dopamine D2 challenge drugs can modulate PE response and reversal learning in AN. In Aim 1., we will apply
a selective dopamine D2 receptor agonist to test its effects on PE and reversal learning. In Aim 2., we will
apply a selective dopamine D2/3 receptor antagonist. We expect that those challenge drugs will lead to
opposite brain and behavior response within groups and directly support the involvement of those receptors in
PE and reversal learning processing. In Aim 3., we will contrast brain and behavior response across challenge
drugs in AN against response in healthy controls to gather pilot data for future investigation. This research will
be important to develop neurotransmitter specific pharmacological treatments for AN.
项目摘要/摘要
神经性厌食症(AN)是一种进食障碍,与体重增加、拒绝进食和
严重的体重减轻。在精神疾病中,AN的死亡率最高;然而,人们对此知之甚少
关于生物标记物,还没有药物被批准用于治疗。许多人只能部分康复,而且
治疗选择,特别是对疾病的心理部分,并不是很有效,强调
需要更有效的治疗方法。
大脑奖励通路对进食的驱动力有直接影响,各种神经成像研究已经
建议更改的奖励处理。神经递质多巴胺在奖赏中起着核心作用。
驱动食物接近的回路,以及多巴胺受体反应和食物之间的动态相互作用
限制可能会对AN的病理生理学产生影响。多巴胺相关的大脑功能已经
间接使用功能磁共振脑成像(FMRI)和提供奖励的任务进行研究
意外的刺激,引发所谓的预测误差(PE)反应。An的研究反复显示
PE过程的改变表明多巴胺回路功能在该疾病中发生了改变。多巴胺与PE
反应也与改变的反转学习有关,这具有重要的治疗意义
对于AS逆转,学习在紊乱中受损,多巴胺系统的调制可能会改善
治疗。然而,在AN中改变PE反应的多巴胺受体机制并没有
已经研究过了。这对开发药物干预措施可能非常重要。
在此应用程序中,我们将制定研究方案并收集试点数据,以确定具体的
多巴胺D2激发药可调节AN的PE反应和逆转学习。在目标1中,我们将申请
一种选择性的多巴胺D2受体激动剂,以测试其对PE和逆转学习的影响。在目标2中,我们将
应用选择性多巴胺D2/3受体拮抗剂。我们预计,这些挑战药物将导致
相反的大脑和群体内的行为反应,并直接支持这些受体参与
PE和反转学习处理。在目标3中,我们将对比大脑和行为在不同挑战中的反应
针对健康对照的药物反应收集试点数据,用于未来的研究。这项研究将
重要的是开发针对AN的神经递质特异性药物治疗。
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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Guido KW Frank其他文献
Guido KW Frank的其他文献
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{{ truncateString('Guido KW Frank', 18)}}的其他基金
Developing a computational electroencephalogram (EEG) paradigm to study prediction error in anorexia nervosa
开发计算脑电图 (EEG) 范式来研究神经性厌食症的预测误差
- 批准号:
9975594 - 财政年份:2020
- 资助金额:
$ 23.63万 - 项目类别:
Developing a computational electroencephalogram (EEG) paradigm to study prediction error in anorexia nervosa
开发计算脑电图 (EEG) 范式来研究神经性厌食症的预测误差
- 批准号:
10224812 - 财政年份:2020
- 资助金额:
$ 23.63万 - 项目类别:
Neural Effects of Negative Affect on Food Choices and Reward Processing In Individuals with Binge Eating Episodes
暴饮暴食个体的食物选择和奖励处理的负面影响的神经效应
- 批准号:
10307096 - 财政年份:2017
- 资助金额:
$ 23.63万 - 项目类别:
Neural Effects of Negative Affect on Food Choices and Reward Processing In Individuals with Binge Eating Episodes
暴饮暴食个体的食物选择和奖励处理的负面影响的神经效应
- 批准号:
10028560 - 财政年份:2017
- 资助金额:
$ 23.63万 - 项目类别:
Neural Effects of Negative Affect on Food Choices and Reward Processing In Individuals with Binge Eating Episodes
暴饮暴食个体的食物选择和奖励处理的负面影响的神经效应
- 批准号:
10053731 - 财政年份:2017
- 资助金额:
$ 23.63万 - 项目类别:
Taste reward circuits and prediction error define eating disorder psychopathology
味觉奖励回路和预测误差定义了饮食失调精神病理学
- 批准号:
8678582 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Taste reward circuits and prediction error define eating disorder psychopathology
味觉奖励回路和预测误差定义了饮食失调精神病理学
- 批准号:
8914714 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Taste reward circuits and prediction error define eating disorder psychopathology
味觉奖励回路和预测误差定义了饮食失调精神病理学
- 批准号:
8824577 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Taste reward circuits and prediction error define eating disorder psychopathology
味觉奖励回路和预测误差定义了饮食失调精神病理学
- 批准号:
9242702 - 财政年份:2014
- 资助金额:
$ 23.63万 - 项目类别:
Brain Reward Circuits and Computational Modeling in Adolescent Anorexia Nervosa
青少年神经性厌食症的大脑奖励回路和计算模型
- 批准号:
8517204 - 财政年份:2012
- 资助金额:
$ 23.63万 - 项目类别:
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