1096 Associations Between Pupillary Light Response and Circadian Rhythm Alterations in Patients with Depressive Disorder

Abstract Introduction Circadian rhythm disruption in depression is associated with neuroendocrine alterations, such as cortisol dysregulation, which increase a vulnerability to affective instability. Yet, how these rhythm abnormalities contribute to the autonomic dysregulation underlying affective symptoms remains unclear. Light-driven pupillary responses reflect both autonomic function and the photic sensitivity of circadian system, offering a window into rhythm–autonomic coupling. This study compared pupillary light responses between depressed patients and non-depressed individuals, and investigated how these responses relate to sleep and circadian rhythm patterns. Methods Participants were recruited from Chosun University Hospital. Depression was diagnosed by a psychiatrist according to DSM-5 criteria, and the Montgomery–Åsberg Depression Rating Scale (MADRS) was used to quantify symptom severity. Thirty-four eligible participants were enrolled and classified into either the depression group (DG; n = 20) or the non-depression group (NDG; n = 14). Actigraphy (CamNtech Ltd., UK; MotionWare 1.3) was worn for ≥7 days, from which sleep parameters and nonparametric rest–activity rhythm indices were derived. Pupillometry was performed using an infrared computerized pupillometer (PLR-3000, NeurOptics Inc., USA) under a standardized light-stimulus paradigm, yielding constriction velocity, redilation velocity, and 75% recovery time. Generalized linear models examined the effects of each sleep/rhythm variable, and their interaction (Group × Variable) on pupillary indices. Results The DG showed lower sleep efficiency (p = .03) and higher fragmentation index (p = .02) compared with the NDG. Pupillometry revealed reduced constriction velocity (p ≈ .04), reduced 75% recovery (p ≈ .04), and relatively higher redilation velocity (p ≈ .03) in the DG. Significant Group × least-active period (L5) interactions were observed across all pupillary metrics (p ≈ .02–.04). Within the DG, a delayed L5 was associated with reduced constriction velocity and 75% recovery, but increased redilation velocity. Conclusion Patients with depression exhibited altered pupillary reactivity to light, characterized by reduced constriction, accelerated redilation, and aberrant recovery, indicating autonomic instability. These patterns were significantly associated with a delayed inactive-rhythm phase (L5), suggesting that circadian phase delay may contribute to altered autonomic control of pupillary responses. Support (if any) This research was supported by the IITP (RS-2025-02219190) grant funded by the Ministry of Science and ICT.