1091 Neuromodulatory Effects of Bright Light on Threat and Reward Network Metabolism in Depressed Adults

Abstract Introduction Light Therapy (LT) is a promising non-pharmacological treatment for depression, however, the mechanisms supporting its therapeutic benefits remain unclear. Preclinical models indicate that light modulates mood through melanopsin-containing of retinal ganglion cells (mRGCs). mRGCs are maximally sensitive to blue light and minimally sensitive to red light, and directly convey light signals from the retina to brain structures involved in threat and reward processing. Using within-scanner light exposures, we examined the degree to which melanopsin-engaging blue (vs. red light and darkness) light modulated regional metabolism within brain regions supporting threat and reward processing in adults with depressive symptoms. Methods A total of 33 young adults (18-30yr, 24.94±3.17yr; 20 Female) with elevated depressive symptoms (Patient Health Questionnaire-95) completed 1 week of a stable sleep schedule followed by an MRI assessment and pupillometry assessment of melanopsin-driven light responsivity (post illumination pupil response). During the MRI protocol, participants underwent pseudo-continuous arterial spin labeling to assess cerebral blood flow (CBF) during dark, blue, and red light exposures lasting approx. 5 minutes; the order of red and blue light was counterbalanced. A mixed effects model evaluated CBF differences in threat (amygdala, insula, ventromedial prefrontal cortex vmPFC) and reward (ventral striatumVS, medial prefrontal cortexmPFC) network regions of interest, adjusting for age, sex, and depression severity. Results Light condition impacted CBF in the VS (F=5.32, p=0.008), mPFC (F=4.41, p=0.017), vmPFC (F=4.63, p=0.014), and insula (F=6.02, p=0.004). Activation was greater in red light versus dark in the VS (p=0.014), mPFC (p=0.020), vmPFC (p=0.017), and insula (p=0.004). There were no significant differences between dark and blue light, or red and blue light, contrary to our predictions. Melanopsin responsivity moderated effects of blue vs red light on CBF (F=5.29, p=0.03), such that greater melanopsin responsivity was associated with greater mPFC CBF under blue but not red light conditions (b=38.7, p=0.05). Conclusion Among individuals with elevated depressive symptoms, bright light exposure may modulate metabolism threat and reward-related brain regions implication in depression pathophysiology in complex ways. Sensitivity of the melanopsin system could play a role in the degree to which blue light modulates affective brain function. Support (if any)