ABSTRACT Adolescent depression is associated with devastating clinical and psychosocial outcomes, and many pediatric depression patients do not respond to existing treatments. With its low cost, minimal side effect profile and efficacy in adult depression, morning bright light therapy (LT) holds promise as a non-medication treatment for adolescent depression. However, maturational differences in the body and brain can alter adolescents’ response to therapeutic doses of adult treatments.Thus, essential first step is to establish whether therapeutic mechanisms underlying antidepressant response to LT in adults translate to adolescents and/or vary with age.Light modulates mood through melanopsin-expressing retinal ganglion cells, which convey light signals from the retina to sub- cortical limbic structures supporting threat (amygdala) and reward (striatum) processing. Antidepressant effects of LT in adults is enhanced by using melanopsin-engaging blue light. Blue-enhanced LT reduces threat-related amygdala activity and increases reward-related striatal activity in healthy adults, and melanopsin-limbic circuits underlie antidepressant effects of light in murine models. Thus, akin to other effective depression treatments, modulation of negative (threat) and positive (reward) neuro-affective mechanisms likely drive clinical benefits of light. Adolescents show higher melanopsin sensitivity to blue light than adults and thus may experience more pronounced effects of blue light on affective brain function. If this notion is supported, it could inform optimized therapeutic dosing of LT for adolescent depression. Light exposures delivered within an MRI scanner engage neuro-affective depression targets in adults, offering an efficient way to probe this therapeutic pathway in adolescence. Using this approach, we propose to test the hypothesis that acute exposure to melanopsin- engaging blue light (vs red light) will stabilize neuro-affective deficits in depressed individuals, and these effects will be stronger for blue light in adolescents than young adults. We will enroll 40 adolescents (12-17yr) and 40 young adults (18-30yr) with depression. As a therapeutic probe, we will examine the direct impact of within- scanner bright light exposures on affective brain function (cerebral blood flow, fMRI). Melanopsin sensitivity will be assessed with pupillometry, and indices of participant developmental, ocular, behavioral and clinical characteristics collected. Our primary aims will test the hypothesis that blue light will stabilize negative (Aim 1: threat) and positive (Aim 2: reward) neuro-affective deficits in depressed participants to a greater extent than red light, and that these effects will vary by developmental stage (adolescent vs adult). Exploratory analyses will 1) examine the extent which melanopic sensitivity explains age differences light-modulated brain function and 2) apply a high-dimensional modeling approach to identify developmental, ocular, beha...