Gains and Losses: Reward Processing in Pediatric Major Depressive Disorder

描述（由申请人提供）：该提案探讨了如何在奖励/惩罚处理涉及的神经和行为机制可能会受到青春期前发病的严重抑郁症（MDD）的影响。体验快乐的问题，即快感缺乏，是MDD的核心组成部分之一。据认为，这种症状与奖励回路中的处理变化有关。也就是说，患有MDD的成年人和青少年在诸如背侧和腹侧纹状体、眶额皮质（OFC）和背外侧前额叶皮质（PFC）等脑区域中显示出对奖励的减弱反应，这些脑区域都已知参与奖励处理。在神经水平上，惩罚处理的改变证据较少，但患有MDD风险增加的女孩在接受惩罚时表现出更强的神经活动，这与行为证据一致，即患有MDD的人对惩罚过敏。虽然青少年和成年MDD患者，甚至有MDD风险的青少年，在奖励处理方面都经历了变化，但尚未确定青春期前MDD病例是否具有类似的奖励/惩罚处理缺陷。参与奖赏处理的区域，如OFC和纹状体在青春期经历了显着的发展，一些研究人员假设，这一发展过程可能有助于通过青春期MDD发病率的快速上升。目前的建议测试的假设，即青春期前的儿童（7-10岁）与MDD，青少年发育的奖励系统之前，是过度反应的惩罚和低反应的奖励相比，健康的同龄人。我们将在一个两阶段的实验中（使用最先进的功能磁共振成像方法和分析技术）从行为和神经水平来检验这一假设，该实验考察这些儿童是否能够根据奖励/惩罚反馈来调整他们的行为，以及在接受糖果奖励和惩罚期间，与奖励/惩罚处理相关的大脑区域内的活动是否在各组之间存在差异。这项工作的成功将提供重要的信息，在发展过程中的神经生物学和行为症状的MDD的连续性。这些信息可能会影响未来治疗方案的开发，这些治疗方案是针对这一患有MDD的人群的特定发育和临床需求而定制的。

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.