Multimodal signature response to light therapy in major depressive disorder – SoLuRep

Major depressive disorders (MDD) are severe disorders with heterogeneous clinical presentations that affect up to 20% of the general population. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light therapy (LT). In meta-analyses, LT has comparable efficacy to antidepressants as a first line treatment of MDD with and without seasonal pattern (SP). Also, LT has the advantage of being effective in improving both sleep, alertness and circadian rhythms, which may be altered in MDD, contrary to antidepressant drugs that target mainly mood. To date, no studies directly evaluated both subjective (questionnaire, sleep diary) and objective markers (actigraphy, night EEG, polysomnography, multiple sleep latency test, melatonin, cortisol, ERG, Pupillometry, measure of corneal light exposure, 7T MRI) of sleep, wake, biological rhythms, and light signaling pathway in all patients with MDD with and without SP. Our hypothesis is that MDD is composed of more homogeneous entities with specific biomarkers on the retina-brain pathways of mood-photic regulation, and so may show differences regarding response to LT. Our objectives are thus to characterize patients suffering from MDD with and without SP, comparing markers on retina-brain pathways of mood-photic regulation at baseline, during and after LT, examining therapeutic response and evolution markers, in order to identify the signature of response to LT and subgroups of responders. We will carry out a multi-centre clinical trial of 173 patients with MDD with and without SP (ratio 1:1) treated 4 weeks with LT with these multimodal approaches and a comparison with 80 healthy controls regarding characteristics and environmental light input. In parallel, photoreceptive and neural pathways mediating the antidepressant effect of LT will be studied in mouse models of MDD exposed to light therapy.