Summary
Our primary hypothesis is that lithium is effective in bipolar disorder because it reduces hypersensitivity to evening light, making individuals less vulnerable to light-induced circadian disruption. If correct, this discovery will back-translate into more precise sub-phenotyping of early-stage bipolar disorder and new and more targeted chronotherapy approaches. We will test:

• the extent to which individuals with bipolar disorder are hypersensitive to the effects of evening light

• whether lithium works via a mechanism that decreases retinal sensitivity to light-induced circadian disruption

• whether there is a microstructural basis in the retina for this hypersensitivity and its attenuation by lithium therapy.

These questions will be addressed at multiple levels of explanation across six complementary workstreams.