Melanopsin-mediated pupillary responses in bipolar disorder-a cross-sectional pupillometric investigation

​Madsen HØ, Ba-Ali S, Heegaard S, Hageman I, Knorr U, Lund-Andersen H, Martiny K, Kessing LV. Melanopsin-mediated pupillary responses in bipolar disorder-a cross-sectional pupillometric investigation. Int J Bipolar Disord. 2021 Mar 1;9(1):7. doi: 10.1186/s40345-020-00211-3. PMID: 33644827; PMCID: PMC7917036.


Background: Visible light, predominantly in the blue range, affects mood and circadian rhythm partly by activation of the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs). The light-induced responses of these ganglion cells can be evaluated by pupillometry. The study aimed to assess the blue light induced pupil constriction in patients with bipolar disorder (BD).

Methods: We investigated the pupillary responses to blue light by chromatic pupillometry in 31 patients with newly diagnosed bipolar disorder, 22 of their unaffected relatives and 35 healthy controls. Mood state was evaluated by interview-based ratings of depressive symptoms (Hamilton Depression Rating Scale) and (hypo-)manic symptoms (Young Mania Rating Scale).

Results: The ipRGC-mediated pupillary responses did not differ across the three groups, but subgroup analyses showed that patients in remission had reduced ipRGC-mediated responses compared with controls (9%, p = 0.04). Longer illness duration was associated with more pronounced ipRGC-responses (7% increase/10-year illness duration, p = 0.02).

Conclusions: The ipRGC-mediated pupil response to blue light was reduced in euthymic patients compared with controls and increased with longer disease duration. Longitudinal studies are needed to corroborate these potential associations with illness state and/or progression.

Keywords: Bipolar disorder; Circadian rhythm; Melanopsin; Mood disorders; Pupillary reflex; Pupillometry; Retina.

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