Gains and Losses: Reward Processing in Pediatric Major Depressive Disorder

得与失：儿科重度抑郁症的奖励处理

基本信息

批准号：
8635389
负责人：
Katherine Rose Luking
金额：
$ 2.89万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8635389
关键词：
Adolescence Adolescent Adolescent Development Adult Affect Age Anhedonia Anterior Area Attenuated Behavior Behavioral Behavioral Mechanisms Behavioral Symptoms Brain region Candy Child Childhood Clinical Corpus striatum structure Data Detection Development Developmental Process Diagnostic Dorsal Feedback Functional Magnetic Resonance Imaging Functional disorder Future Gambling Incidence Individual Individual Differences Insula of Reil Intervention Link Major Depressive Disorder Measures Mental Depression Metric Neurobiology Pathway interactions Population Prefrontal Cortex Process Puberty Punishment Research Research Personnel Reversal Learning Rewards Risk Severities Severity of illness Stimulus Symptoms System Techniques Testing Ventral Striatum Work base cingulate cortex depressive symptoms dopamine system effective intervention effective therapy experience frontal lobe girls hedonic high risk imaging modality neurodevelopment neuromechanism peer pleasure prepuberty relating to nervous system research study response reward circuitry reward processing success theories

项目摘要

DESCRIPTION (provided by applicant): This proposal explores how the neural and behavioral mechanisms involved in reward/punishment processing may be affected in pre-puberty onset Major Depressive Disorder (MDD). Problems experiencing pleasure, anhedonia, is one of the core components of MDD. It is thought that this symptom is related to changes in processing within the reward circuitry. Namely adults and adolescents with MDD show attenuated response to reward in brain regions such as the dorsal and ventral striatum, orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (PFC), all known to be involved in reward processing. There is less evidence for alterations in punishment processing at the neural level, but girls at increased risk for developing MDD show increased insula activity when receiving punishments, which aligns with behavioral evidence that individuals with MDD are hypersensitive to punishment. While it seems clear that adolescents and adults with MDD, and even adolescents at risk for MDD, experience changes in reward processing, it has yet to be determined whether pre- puberty cases of MDD are characterized by similar reward/punishment processing deficits. Regions involved in reward processing such as the OFC and striatum undergo significant development over the course of puberty and some researchers have hypothesized that this developmental process could contribute to the rapid rise in incidence of MDD through adolescence. The current proposal tests the hypothesis that pre-puberty children (7-10 years) with MDD, prior to adolescent development of reward systems, are hyper-responsive to punishments and hypo-responsive to rewards compared to healthy peers. We will test this hypothesis both behaviorally and at the neural level in a two-session experiment (using state-of-the-art functional magnetic resonance imaging methods and analytical techniques) that examines whether these children are able to adjust their behavior based on reward/punishment feedback and whether activity within brain regions associated with reward/punishment processing is different between groups during receipt of candy rewards and punishments. Success in this work would provide important information about the continuity of the neurobiological and behavioral symptoms of MDD over the course of development. This information could impact development of future treatment options tailored to the specific developmental and clinical needs of this population struggling with MDD.

描述（由申请人提供）：该提案探讨了奖励/惩罚处理所涉及的神经和行为机制如何在peberty发作前重大抑郁症（MDD）中受到影响。遇到愉悦的问题，阿内多尼亚（Anhedonia）是MDD的核心组成部分之一。据认为，这种症状与奖励电路内处理的变化有关。即具有MDD的成年人和青少年表现出对大脑区域的奖励的减弱反应，例如背侧和腹侧纹状体，轨道额叶皮层（OFC）和背侧前额叶皮层（PFC），所有这些都涉及奖励处理。有较少的证据表明在神经层面上进行惩罚处理的改变，但是在接受惩罚时，患有MDD风险增加的女孩表明，隔离活动增加了，这与行为证据表明患有MDD的人对惩罚过敏。虽然很明显，有MDD的青少年和成年人，甚至是有MDD风险的青少年，奖励处理的经验变化，但尚未确定MDD的青春期前病例是否具有类似的奖励/惩罚处理赤字的特征。在青春期和一些研究人员的过程中，参与奖励处理（例如OFC和纹状体）等奖励处理的地区经历了重大的发展。当前的提案检验了以下假设：与健康同伴相比，在青少年发展奖励系统之前，Puberty儿童（7-10岁）在青少年发展奖励系统之前，对惩罚和低响应性的奖励是非常反应的。我们将在两次课程实验（使用最先进的功能性磁共振成像方法和分析技术）中在行为和神经水平上检验该假设，该实验检查这些孩子是否能够基于奖励/惩罚反馈来调整其行为，以及在奖励/惩罚处理中与奖励/惩罚处理相关的大脑区域的活动是否有所不同。这项工作的成功将提供有关MDD在发展过程中神经生物学和行为症状的连续性的重要信息。这些信息可能会影响针对与MDD斗争的该人群的特定发展和临床需求量身定制的未来治疗方案的发展。