Neurobehavioral Targets of Mindfulness in Youth At Risk for Mood Disorders

情绪不稳定，定义为情绪频繁且夸张的变化，是一个重要的跨诊断症状 这会导致严重的损害并增加自杀风险。这种症状是情绪低落的常见前兆 疾病发作，尤其是有家族风险的青少年。由于青春期是情绪障碍发病的高峰期 也是神经可塑性的重要窗口，可能是干预降低情绪的最佳时机 不稳定性。对青少年的荟萃分析发现，基于正念的干预措施（MBI）会降低情绪 症状并改善情绪/行为失调，与情绪不稳定密切相关的构建；然而， 这些影响的神经/行为机制尚不清楚。重要的是要了解如何以及为谁 MBI 致力于设计干预措施，更有效地吸引适当的目标并为这些目标提供治疗 最有可能受益。在成人中，MBI 已被证明可以增加静息态功能连接 (rsFC) 后扣带回（PCC）和额顶控制网络（FPCN）之间的神经回路 提高对走神现象的认识。无意识走神、思维错误的行为指标 研究还发现，MBI 后的持续注意力响应任务 (SART) 会有所下降。自从 无意识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，改善压力反应并降低情绪不稳定性。确实， 先前的研究已将 PCC-FPCN rsFC 的增加与焦虑减少和焦虑的下游影响联系起来。 抑郁症；我们最近在青少年中进行的试点研究发现，预测 PCC-FPCN rsFC 中 MBI 相关的增加 随后情绪不稳定性降低。鉴于这些有希望的试点数据，下一步是进行随机 对照试验评估 MBI 对走神相关目标和情绪不稳定性的特定影响。在样本中 针对 100 名情绪不稳定的青少年（11-13 岁）和患有严重情绪障碍的父母，我们建议 测试是否：(1) 8 周 MBI（与对照相比）改变了与走神相关的目标（PCC-FPCN rsFC、SART 性能）； （2）走神措施的改变导致情绪不稳定性减轻； (3) 摄入思想- 徘徊测量可预测不同的 MBI 效益。参与者将被随机化——按非情绪分层 DSM-5 诊断和青春期性别状态 – 8 周 MBI 或对照。我们将在 4 周前扫描青少年 干预后、干预后立即和干预后 3 个月，以评估以下变化之间的纵向关系： PCC-FPCN rsFC 和行为/临床测量。行为/临床结果也将在 9 点进行评估 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维持积极情绪的能力。这个设计将使我们能够评估， 通过时间精度和跨层次的分析，减少无意识走神对人的影响 随后的情绪不稳定，重点关注高危青少年的关键发展时期；也将使我们能够 评估谁将从 MBI 中受益最多，转向个性化医疗方法。

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.