Gains and Losses: Reward Processing in Pediatric Major Depressive Disorder

描述(由申请人提供)：这项建议探索了在青春期前发作的严重抑郁障碍(MDD)中，涉及奖惩处理的神经和行为机制可能会受到怎样的影响。问题体验快感、快感缺失是MDD的核心组成部分之一。据认为，这种症状与奖赏回路内处理过程的变化有关。也就是说，患有MDD的成年人和青少年在大脑的背侧和腹侧纹状体、眼眶前额叶(OFC)和背外侧前额叶(PFC)等脑区对奖赏的反应减弱，所有这些都是已知参与奖赏加工的区域。较少的证据表明惩罚处理在神经层面上发生了变化，但患MDD风险增加的女孩在接受惩罚时表现出脑岛活动增加，这与患有MDD的个体对惩罚敏感的行为证据相一致。虽然似乎很明显，患有MDD的青少年和成人，甚至是有MDD风险的青少年，都会经历奖励加工的变化，但尚不确定青春期前的MDD病例是否具有类似的奖励/惩罚加工缺陷的特征。参与奖赏处理的区域，如OFC和纹状体，在青春期过程中经历了显着的发展，一些研究人员假设，这种发展过程可能导致青春期MDD发病率的迅速上升。目前的提案测试了一种假设，即与健康的同龄人相比，患有MDD的青春期前儿童(7-10岁)在青春期奖励系统发育之前，对惩罚反应强烈，对奖励反应迟钝。我们将在一个为期两个阶段的实验(使用最先进的功能磁共振成像方法和分析技术)中从行为和神经层面检验这一假设，该实验检查这些儿童是否能够根据奖惩反馈调整他们的行为，以及在接受糖果奖惩期间，与奖惩处理相关的大脑区域的活动是否在不同组之间有所不同。这项工作的成功将提供有关MDD在发育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这一与MDD作斗争的人群的特定发展和临床需求而定制的未来治疗方案的发展。

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.