Comparing reward learning among adolescents and adults with MDD and using reward-related neurobiology to predict future reward-related learning

项目摘要 青少年中的精神健康问题和疑似自杀企图的紧急就诊次数 2021年期间，美国儿童和青少年学会宣布全国进入紧急状态。 精神病学。在青春期发作的重性抑郁症（MDD）的后果是巨大的。 患有MDD的青少年有较高的自杀风险，这是该年龄组的第二大死亡原因， 在成年期发展出额外的精神疾病尽管付出了巨大的努力，黄金的功效- MDD的标准治疗仍然很低。由于这些原因，研究的目的是确定早期神经生物学 与抑郁症发作和严重程度相关的标志物。神经影像学领域的进展已经确定了异常的 奖励电路（即，在预期或接收奖励时抑制奖励系统中的激活）作为潜在的 抑郁症的内在表型然而，奖励处理并不局限于享乐主义，抑郁可能 更好地描述了减少的快乐如何影响奖励系统的其他方面，例如奖励 学习先前的文献支持MDD与抑制奖励学习行为相关的观点 然而，关于青少年奖励学习行为如何受到MDD的影响，我们知之甚少。的 注意，研究青少年时期的奖励功能障碍和奖励学习是至关重要的，因为奖励的提高 敏感性和持续的神经可塑性发生在这段时间。本提案的目的是研究如何 奖励学习在青少年时期受到MDD的影响，以及奖励的神经生物学机制 反应性和奖励回路预测成年后的奖励学习行为。第一个目标是成为 第一项研究比较青少年和成年人与非MDD的奖励学习行为。然后， 利用现有的数据集，第二个目标是评估青少年之间的联系， 神经生物学奖励反应性，奖励系统的静息状态功能连接（rsFC），以及任务- 基于功能连接和未来奖励学习。填补了我们对奖励如何 学习受到青少年MDD的影响，以及奖励回路的神经生物学机制如何与 未来的奖励驱动行为可能会进一步加深我们对抑郁症风险的理解，并有助于早期告知 预防工作。对这些机制的更好理解也可能有助于告知个体化 基于个体神经生物学和行为的青少年治疗策略。

PROJECT SUMMARY The number of mental health concerns and emergency visits for suspected suicide attempts in youth during 2021 has led to a declared national emergency by the American Academy of Child and Adolescent Psychiatry. The consequences of major depressive disorder (MDD) onset during adolescence are substantial. Adolescents with MDD are at higher risk for suicidality, the second leading cause of death in this age group, and for developing additional mental health disorders in adulthood. Despite considerable efforts, efficacy of gold- standard treatment for MDD remains low. For these reasons, research has aimed to identify early neurobiological markers related to depression onset and severity. Progress in the field of neuroimaging has identified aberrant reward circuitry (i.e., dampened activation in the reward system in anticipation or receipt of reward) as a potential endophenotype for depression. However, reward processing is not limited to hedonics, and depression may be better characterized by how diminished hedonics impact other aspects of the reward system, such as reward learning. Previous literature supports the notion that MDD is associated with dampened reward-learning behavior in adults; however, less is known about how adolescent reward-learning behavior may be impacted by MDD. Of note, studying reward dysfunction and reward learning during adolescence is critical due to heightened reward sensitivity and ongoing neuroplasticity occurring during this time. The goal of this proposal is to examine how reward learning is impacted by MDD in adolescence, as well as how neurobiological mechanisms of reward responsivity and reward circuitry predict future reward-learning behavior in adulthood. The first aim is to be the first study to compare reward-learning behavior among adolescents and adults with and without MDD. Then, capitalizing on an existing dataset, the second aim is to assess the associations between adolescent neurobiological reward responsivity, resting-state functional connectivity (rsFC) of the reward system, and task- based functional connectivity and future reward learning. Filling the gap in our understanding of how reward learning is impacted by MDD in adolescents and how neurobiological mechanisms of reward circuitry relate to future reward-driven behavior may further our understanding of risk for depression and help to inform early prevention efforts. Improved understanding of these mechanisms also may help to inform individualized treatment strategies for youth based on individual neurobiology and behavior.