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HELIOS-BD

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

As featured on STV: watch here

VISION

Investigating Lithium and Light in Bipolar Disorder

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.

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AIMS

We will test whether people with bipolar disorder are hypersensitive to evening light stimuli and whether Lithium may act to counter this.

CIRCADIAN RHYTHM

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.

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LIGHT SENSITIVITY

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.

WORKSTREAM 1

Retinal Organoids

Hypothesis: Retinal organoids (mini organs produced in vitro) derived from patients with bipolar disorder exhibit hypersensitivity to light (relative to retinal organoids from controls) and this hypersensitivity is attenuated by lithium exposure.

Image by Umesh Soni
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WORKSTREAM 2

Melatonin Supression and Lithium

Hypothesis: The administration of lithium to people with no history of mental illness reduces the magnitude of non-visual responses to light at night stimuli, assessed by the light-induced suppression of melatonin

Workstream 2 In Numbers

45

PARTICIPANTS

400mg

LITHIUM

600 LUX

MELANOPIC EDI

5

DAYS

WORKSTREAM 3

Bipolar Disorder, Melatonin Supression and Lithium

Hypothesis: People with bipolar disorder (relative to controls) exhibit greater non-visual responses to light at night stimuli (assessed by the light-induced suppression of melatonin) and these responses are attenuated for those on lithium therapy.

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WORKSTREAM 4

Retinal Sensitivity in People with Bipolar Disorder

Retinal Sensitivity and Lithium Therapy

Hypothesis: people with bipolar disorder (relative to controls) exhibit greater retinal sensitivity to evening light stimuli and this sensitivity is attenuated for those on lithium

therapy.

WORKSTREAM 5

RETINA MICROSTRUCTURE

Hypothesis: there are microstructural changes in the retina in people with bipolar disorder and these differences are modified by lithium therapy.

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Image by Surface

WORKSTREAM 6

LIVED EXPERIENCE CO-PRODUCTION

A cross-cutting Workstream 6 will focus on the co-production of project design

and assessments, knowledge exchange and dissemination activities at each stage.

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