Lithium's mechanism in bipolar disorder: investigating the light hypersensitivity hypothesis

Lithium has been in use for 70 years and is the most effective treatment for bipolar disorder. It has many actions but the precise mechanism of action in bipolar disorder is uncertain. Recent evidence suggests that lithium may work by stabilizing aberrant circadian rhythms of mood, cognition and rest/activity, possibly via an action at the level of the retina. Specifically, individuals with bipolar disorder who are hypersensitive to the destabilizing effects of excess light in the evening may respond to lithium because it acts on the retina to make light-induced circadian disruption less likely. This is a plausible and exciting hypothesis that, if true, could herald a new era of chronotherapeutic approaches. We will test whether people with bipolar disorder are hypersensitive to evening light stimuli and whether lithium works by increasing retinal resilience to light-induced circadian disruption. In parallel, we will test the effect of light stimuli and lithium treatment on retinal organoid cells derived from individuals with bipolar disorder. People with bipolar disorder are involved in every aspect of this project, from design to dissemination, and we will also co-produce a range of knowledge exchange activities on the theme of 'Bipolar Disorder, Lithium and Light'.