Neurobehavioral Targets of Mindfulness in Youth At Risk for Mood Disorders

心境不稳是一种重要的转诊症状， 导致严重损伤并增加自杀风险。这种症状是情绪的常见前兆 疾病发作，特别是在有家族风险的青年中。由于青春期是心境障碍发病的高峰期 也是神经可塑性的一个重要窗口，这可能是干预降低情绪的最佳时机 不稳定。青年荟萃分析发现，基于正念的干预（MBIs）会降低情绪 症状和改善情绪/行为失调，与情绪不稳定密切相关的结构;然而， 这些影响的神经/行为机制是未知的。必须了解如何以及为谁 MBIs的工作，设计干预措施，更有效地参与适当的目标和提供治疗， 最有可能受益。在成人中，MBI已被证明可以增加静息状态功能连接（rsFC） 在后扣带回（PCC）和额顶控制网络（FPCN）之间，神经回路可能 有助于意识到走神。无意走神的行为指标， 持续注意反应任务（SART）也被发现在MBI之后减少。以来 无意的走神会放大负面影响，意识到走神可能会促进适应性 使用情绪调节策略，从而改善压力反应和降低情绪不稳定性。的确， 先前的研究已经将PCC-FPCN rsFC增加与焦虑减少的下游效应联系起来， 抑郁症;我们最近在青年中进行的初步研究发现，MBI相关的PCC-FPCN rsFC增加预测了 后来情绪不稳定的减少。鉴于这些有希望的试点数据，下一步是进行随机 对照试验，以评估MBI对走神相关目标和情绪不稳定性的特定影响。样品中 在100名情绪不稳定的青少年（11-13岁）中，我们建议 测试是否：（1）8周MBI（与对照组相比）改变了与走神相关的目标（PCC-FPCN rsFC，SART （2）在走神措施的变化导致情绪不稳定性减少;（3）摄入量的心- 游荡措施预测差异MBI效益。受试者将随机分组-根据非情绪分层 DSM-5诊断和青春期状态的性别-至8周MBI或对照。我们将在4周前扫描青年 干预后即刻和干预后3个月，以评估 PCC-FPCN rsFC和行为/临床测量。行为/临床结局也将在9时进行评估 干预后几个月。我们将通过自我报告和生态瞬时评估来评估情绪不稳定性， 关注负面情绪的变化和保持积极情绪的能力。这个设计可以让我们评估， 随着时间的精确性和跨层次的分析，减少无意的走神对 随后的情绪不稳定，重点放在一个关键的发展时期，在高危青年，也将使我们能够 评估谁将从MBIs中受益最多，走向个性化医疗方法。

Mood lability, defined as frequent and exaggerated changes in mood, is an important transdiagnostic symptom that causes significant impairment and increases suicide risk. This symptom is a common precursor to mood disorder onset, particularly in youth at familial risk. Since adolescence is a peak period for mood disorder onset and an important window of neural plasticity, it may be an optimal time for an intervention to decrease mood lability. Meta-analyses in youth have found that mindfulness-based interventions (MBIs) decrease mood symptoms and improve emotion/behavioral dysregulation, constructs closely related to mood lability; however, neural/behavioral mechanisms of these effects are unknown. It is essential to understand how and for whom MBIs work, to design interventions that more efficiently engage appropriate targets and deliver treatment to those most likely to benefit. In adults, MBIs have been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate (PCC) and the frontoparietal control network (FPCN), neural circuitry which may subserve awareness of mind-wandering. A behavioral indicator of unintentional mind-wandering, errors on the Sustained Attention to Response Task (SART), has also been found to decrease following MBIs. Since unintentional mind-wandering amplifies negative affect, awareness of mind-wandering may facilitate the adaptive use of emotion regulation strategies, leading to improved stress response and decreased mood lability. Indeed, previous studies have linked increased PCC-FPCN rsFC to downstream effects of decreased anxiety and depression; and our recent pilot study in youth found that MBI-related increases in PCC-FPCN rsFC predicted later decreases in mood lability. Given these promising pilot data, the next step is to conduct a randomized controlled trial to assess MBI-specific effects on mind-wandering related targets and mood lability. In a sample of 100 adolescents (11-13 years old) with mood lability and a parent with a major mood disorder, we propose to test whether: (1) an 8-week MBI (vs. control) modifies mind-wandering-related targets (PCC-FPCN rsFC, SART performance); (2) changes in mind-wandering measures lead to less mood lability; and (3) intake mind- wandering measures predict differential MBI benefit. Participants will be randomized – stratified on non-mood DSM-5 diagnosis and sex-by-pubertal status – to an 8-week MBI or control. We will scan youth before, 4 weeks into, immediately after, and 3 months after intervention to assess longitudinal relationships amongst changes in PCC-FPCN rsFC and behavioral/clinical measures. Behavioral/clinical outcomes will also be assessed at 9 months post-intervention. We will assess mood lability via self-report and ecological momentary assessment, focusing on variability in negative affect and ability to sustain positive mood. This design will allow us to assess, with temporal precision and across levels of analysis, the impact of decreasing unintentional mind-wandering on subsequent mood lability, focusing on a crucial developmental period in at-risk youth; and will also allow us to assess who will benefit most from MBIs, moving toward a personalized medicine approach.