2026-10-14T06:48:11Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34023930 2026-09-29T13:34:52Z category_24538 category_30388 item_type_5 month_year_09_2026

Cone- and melanopsin-mediated pupil responses in bipolar disorder and lithium treatment Joel Martin (11864048) Psychiatry (incl. psychotherapy) Sensory processes, perception and performance Pupillometry Melanopsin Bipolar disorder Post-illumination pupil response Silent substitution Background: Circadian dysregulation and altered sensitivity to light are implicated in bipolar disorder and may reflect changes in retinal photic signalling. Lithium is an effective mood stabiliser with known influence on circadian rhythms, but its precise therapeutic mechanism remains poorly understood.Aims/Objectives: To conduct an interim analysis of HELIOS-BD data to examine whether bipolar disorder and lithium treatment are associated with altered dark- and light-adapted pupillary indices of retinal light sensitivity, relative to healthy controls.Methods: Pupil responses were recorded in 50 healthy controls, 36 individuals with bipolar disorder receiving lithium therapy, and 48 individuals with bipolar disorder not receiving lithium therapy, matched closely for age and sex (target n = 60 for each group). Under dark-adapted conditions, the post-illumination pupil response (PIPR) was elicited using narrowband pulses of long- (629 nm) and short-wavelength light (478 nm). Under light-adapted conditions around a photopic background (~173.47 cd/m2), silent substitution stimuli were used to selectively modulate cone or melanopsin excitation. Outcome metrics capturing melanopsin- and cone-mediated components were analysed using linear regression models adjusting for age and baseline pupil diameter.Results: In this interim analysis conducted in February 2026, no statistically significant group differences were observed for PIPR, the light-adapted cone-mediated response or the melanopsin-mediated response. Bipolar participants receiving lithium showed numerically smaller melanopsin-mediated responses than controls (PIPR: β = -0.277, 95% CI [-2.35, 1.79]; Mel: β = -6.65, 95% CI [-23.75, 10.46]), but effect estimates were imprecise and confidence intervals overlapped across groups. Overall, the interim findings provide no evidence of altered cone- or melanopsin-mediated pupil responses in bipolar disorder.Impact statement: When data collection is complete (est. July 2027), this will be the largest study of pupillary light responses in euthymic bipolar disorder. Whilst the general direction of effects seems unlikely to change for pre-planned analyses, emerging evidence suggests that secondary analyses incorporating age, sex and chronotype may reveal a more nuanced picture of light sensitivity in bipolar disorder. 2026-09-29T13:34:52Z Image Poster 10.6084/m9.figshare.34023930.v1 https://figshare.com/articles/poster/_p_dir_ltr_Cone-_and_melanopsin-mediated_pupil_responses_in_bipolar_disorder_and_lithium_treatment_p_/34023930 CC BY 4.0