<p dir="ltr">Cone- and melanopsin-mediated pupil responses in bipolar disorder and lithium treatment</p>

Lithium is an effective mood stabiliser with known influence on circadian rhythms, but its precise therapeutic mechanism remains poorly understood.</p><p dir="ltr"><b>Aims/Objectives: </b>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.</p><p dir="ltr"><b>Methods: </b>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 <i>n</i> = 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.</p><p dir="ltr"><b>Results:</b> 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.