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

摘要

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.