LAUSR

Light therapy is a first line treatment for seasonal depression but is not effective for everyone. Understanding mechanisms of light therapy may help predict who will successfully respond to treatment. Individual differences in the retina’s responsivity to light may underlie differences in treatment response given prior work linking reduced retinal responsivity in seasonal depression. This study tested if retinal responsivity changed across a light therapy intervention and whether changes in retinal responsivity were associated with improved depression. Participants diagnosed with Major Depressive Disorder, With Seasonal Pattern were randomized to 6 weeks of light therapy or cognitive behavioral therapy for seasonal affective disorder (CBT-SAD). Participants in the light therapy group (N=52) were on average 41.9 years (SD=14.8) and predominantly women (72%). Retinal responsivity was assessed using the post-illumination pupil response (PIPR), measured mid-day in winter pre- and post-treatment. The net PIPR (red minus blue) was calculated as a percent of baseline 10-30 seconds post stimulus. Depression severity was measured using the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder version (SIGH-SAD). Using multilevel models, we tested 1) if the PIPR changed from pre- to post-treatment and 2) if changes in the PIPR predicted improvements in depression. All analyses included a random intercept of participant ID and controlled for age, gender, time of testing, and the pupillary light reflex (PLR). There was a significant main effect of time on the PIPR, such that PIPR increased from pre- to post-light treatment (b=0.29; SE=0.13; p=0.03). There was a significant negative association between changes in PIPR and changes in depression, such that increases in PIPR were associated with decreases in depression symptom severity (b= -0.18; SE=0.06; p=0.01). Retinal responsivity increased across a light therapy intervention and increases in retinal responsivity were associated with improved depression. It is possible an upregulation in retinal responsivity drives antidepressant effects of light therapy, either through direct or circadian pathways. However, changes in retinal responsivity measured throughout treatment are required to discern whether these changes are mechanistic.