Morning Light Treatment for Traumatic Stress: the Role of Amygdala Reactivity

晨光治疗创伤性应激：杏仁核反应性的作用

• 批准号: 9807446
• 负责人: Helen Julia Burgess
• 金额: $ 80.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9807446
• 关键词: Address; Amygdaloid structure; Anatomy; Animals; Anxiety; Arousal; Basic Science; Biological; Brain; Case Study; Clinical; Clinical Trials; Cues; DSM-V; Data; Deep Brain Stimulation; Devices; Dose; Emotional; Enrollment; Face; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Hamilton Rating Scale for Depression; Hour; Human; Individual; Intervention; Lead; Light; Link; Measures; Mental Depression; Mental Health; Moods; National Institute of Mental Health; Participant; Pathology; Patient Self-Report; Phase; Photoreceptors; Photosensitivity; Phototherapy; Physiologic pulse; Pilot Projects; Placebos; Post-Traumatic Stress Disorders; Psychotherapy; Randomized; Research; Retinal; Retinal Ganglion Cells; Retinal Photoreceptors; Rodent Model; Role; Signal Transduction; Strategic Planning; Stress; Symptoms; Testing; Therapeutic; Time; Translating; Translations; Trauma; Work; circadian; cognitive task; experience; functional MRI scan; functional outcomes; male; novel; optimal treatments; pilot trial; randomized trial; reduce symptoms; relating to nervous system; response; side effect; social stigma; stress symptom; symptomatic improvement; trauma exposure; treatment adherence; treatment duration; treatment effect; treatment risk

ABSTRACT Exposure to trauma can lead to posttraumatic stress disorder (PTSD), depression and anxiety. Although therapies exist for traumatic stress, many individuals fail to receive treatment or remain symptomatic despite treatment. New treatments are needed for traumatic stress that target underlying mechanisms of the pathology and offer a safe and acceptable alternative. Morning bright light has good potential as a novel non-invasive, low risk treatment for traumatic stress. Morning bright light treatment has been shown to reduce depression, anxiety, and PTSD symptoms (including our own pilot data). However, no studies are exploring the therapeutic mechanisms of bright light treatment for traumatic stress. Retinal circadian photoreceptors transmit light to the brain, including direct projections to the amygdala. In healthy controls, a 3-week morning bright light treatment reduced amygdala reactivity to an emotional faces fMRI task. Amygdala reactivity to negative cues is linked to traumatic stress symptoms, and reduces after successful treatment. Thus, morning bright light treatment may reduce traumatic stress by reducing amygdala reactivity. Using a transdiagnostic approach, we will enroll subjects who have experienced a criterion A trauma in the past 5 years and display significant mood and arousal symptoms. We will use the commercially available Retimer® bright light device, which optimizes the therapeutic light wavelength. Treatment adherence will be objectively assessed. In the R61 phase, 66 subjects will be randomized to 4 weeks of bright morning light at 3 different doses: 15 min or 30 min or 1 hour/day. Amygdala reactivity (probed with fMRI emotional faces task) will be assessed at 3 time points: baseline, 2 weeks, and 4 weeks. We will test for a dose-response relationship between duration of daily morning light pulse and change in amygdala reactivity from baseline to 2 and 4 weeks. R61 Aim (Target Engagement): establish a significant dose response relationship between duration of daily morning light pulse and reduction from baseline in amygdala reactivity at week 2 and/or week 4. Morning bright light must induce a meaningful reduction (d≥0.5) in amygdala reactivity to proceed to the R33 (the go/no-go criteria). In the R33 phase, 122 subjects will be randomized to bright (active) vs. dim (credible and biologically inactive placebo) morning light, with optimal treatment duration derived from the R61 phase (minimal duration of daily morning light pulse that elicits the earliest meaningful reduction of d≥0.5 in amygdala reactivity). R33 Aim 1 (Functional Outcomes): establish the effect of morning bright vs. dim (placebo) light treatment on traumatic stress symptoms using standard and transdiagnostic clinical measures. R33 Aim 2: establish change in amygdala reactivity as a predictor of traumatic stress symptom improvement. This project will be the first to establish if anatomical links between the retinal circadian photoreceptors and amygdala translate into clinically meaningful changes in amygdala reactivity using morning bright light therapy. This research will lay the foundation for developing morning bright light treatment as a novel treatment for traumatic stress.

摘要 暴露于创伤会导致创伤后应激障碍（PTSD），抑郁和焦虑。虽然 创伤性应激障碍的治疗存在，许多人未能接受治疗或保持症状， 治疗创伤性应激需要新的治疗方法，以病理学的潜在机制为目标 并提供一个安全和可接受的替代方案。晨光作为一种新型的非侵入性， 低风险的创伤性压力治疗早晨明亮的光线治疗已被证明可以减少抑郁症， 焦虑和PTSD症状（包括我们自己的试点数据）。然而，没有研究探索治疗 强光治疗创伤应激的机制。视网膜昼夜光感受器将光传输到 大脑，包括直接投射到杏仁核。在健康对照组中， 杏仁核对情绪化面部功能磁共振成像任务的反应性降低。杏仁核对负面线索的反应与 创伤应激症状，并在成功治疗后减轻。因此，早晨明亮的光线治疗可能会 通过减少杏仁核的反应来减轻创伤压力。使用跨诊断方法，我们将招募 受试者在过去5年中经历了标准A创伤，并表现出显著的情绪， 性唤起症状我们将使用市售的Retimer®亮光设备，该设备优化了 治疗光波长将客观评估治疗依从性。在R61阶段，66名受试者 将被随机分配到3种不同剂量的4周明亮的晨光中：15分钟或30分钟或1小时/天。 将在3个时间点评估杏仁核反应性（使用fMRI情绪面孔任务探测）：基线、2 周，4周。我们将测试每天早晨光照时间与 脉搏和杏仁核反应性从基线到2周和4周的变化。R61瞄准（目标交战）： 在每日早晨光脉冲持续时间和减少之间建立显著剂量反应关系 在第2周和/或第4周时，杏仁核反应性与基线相比。早晨明亮的光线必须引起一个有意义的 杏仁核反应性降低（d≥0.5），以进入R33（通过/不通过标准）。在R33阶段，122 将受试者随机分为明亮（活性）和昏暗（可信的和生物学上无活性的安慰剂）的晨光， 具有从R61阶段获得的最佳治疗持续时间（每天早晨光脉冲的最小持续时间， 在杏仁核反应性中d≥0.5的最早有意义的降低）。R33目标1（功能结局）： 使用以下方法确定早晨明亮与昏暗（安慰剂）光治疗对创伤性应激症状的影响 标准和跨诊断临床测量。R33目标2：将杏仁核反应性的变化确定为 创伤应激症状改善的预测因子这个项目将是第一个建立解剖学联系的项目， 视网膜昼夜光感受器和杏仁核之间的联系转化为临床意义的变化， 杏仁核反应性使用早晨明亮的光疗法。本研究为进一步开发 早晨明亮的光治疗作为一种新的治疗创伤性应激反应。