Gains and Losses: Reward Processing in Pediatric Major Depressive Disorder

描述（由申请人提供）：本研究旨在探讨青春期前发病的重度抑郁症（MDD）的奖罚加工的神经和行为机制。体验快乐的问题，快感缺乏，是重度抑郁症的核心组成部分之一。人们认为这种症状与奖赏回路中处理过程的变化有关。也就是说，患有重度抑郁症的成人和青少年在大脑的背侧纹状体和腹侧纹状体、眶额皮质（OFC）和背外侧前额皮质（PFC）等区域对奖励的反应减弱，这些区域都参与了奖励处理。很少有证据表明神经层面的惩罚处理发生了改变，但患重度抑郁症风险增加的女孩在接受惩罚时表现出增加的脑岛活动，这与重度抑郁症患者对惩罚极度敏感的行为证据相一致。虽然青少年和成年MDD患者，甚至是有MDD风险的青少年，在奖励处理方面都经历了变化，但青春期前的MDD患者是否也有类似的奖励/惩罚处理缺陷还有待确定。与奖励处理有关的区域，如OFC和纹状体，在青春期经历了显著的发育，一些研究人员假设，这一发育过程可能导致青春期MDD发病率的迅速上升。目前的提议验证了一个假设，即青春期前（7-10岁）患有重度抑郁症的儿童，在青春期奖励系统发育之前，与健康的同龄人相比，对惩罚的反应过度，对奖励的反应较低。我们将在两个阶段的实验中（使用最先进的功能磁共振成像方法和分析技术）在行为和神经水平上验证这一假设，以检查这些儿童是否能够根据奖罚反馈调整他们的行为，以及在收到糖果奖罚时，与奖罚处理相关的大脑区域的活动是否在各组之间有所不同。这项工作的成功将为重度抑郁症在发展过程中的神经生物学和行为症状的连续性提供重要信息。这一信息可能会影响未来治疗方案的发展，以适应这些与重度抑郁症斗争的人群的具体发展和临床需求。

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.