Examining Lithium's Mechanism in Bipolar Disorder

NCT07750925 | Not Yet Recruiting DMC

• 2 other identifiers: 333056226787/Z/22/Z
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the current study is to examine the acute effect of lithium on the visual and non-visual responses to light in a sample of healthy participants. Our experiments will investigate the effects of lithium on light sensitivity at the level of the retina as well as central visual and non-visual pathways. Our primary hypothesis is that the administration of lithium to healthy volunteers will reduce the magnitude of a range of non-visual responses to light including melatonin suppression, alertness, performance, mood and electrophysiology in a manner that is dependent of the amount of lithium in the brain. To better understand the postulated effects of lithium on light sensitivity and to examine its relationship at the level of the retina, we will assess the visual and non-visual responses to light, as well as the distribution of lithium in the brain using a non-invasive imaging technique. In addition to that, we also aim to examine the impact of both lithium and light on a molecular level through whole blood transcriptome sequencing.

Conditions

Healthy; Bipolar

Keywords

Circadian Rhythms; Performance; Mood; Lithium; Light sensitivity

Outcome Measures

Primary Outcomes (2)

• Plasma melatonin change in response to light stimulation

  Difference in plasma melatonin suppression following light exposure between the no-lithium and lithium conditions.

  Measured during the 90-minute light exposure session after 7 days of lithium treatment and after 7 days in the no-lithium condition (days 9-11 and 19-21).

• Brain lithium signal intensity measured by 7Li-MRI

  Quantification of brain lithium signal intensity using 7Li magnetic resonance imaging following 9 days of lithium carbonate administration in healthy participants.

  Measured once following 9 days of lithium carbonate administration (Day 21)

Secondary Outcomes (10)

• Difference in colour vision post-light exposure between lithium and no-lithium conditions

  Measured immediately following the 90-minute light exposure session after 7 days in the lithium condition and after 7 days in the no-lithium condition (days 9-11 and 19-21)

• Waking EEG Measures

  EEG recordings will occur pre, post and throughout the 90-minute light exposure during days 9-11 and 19-21. EEG recordings will be conducted hourly when the participant is awake in the laboratory.

• Pittsburgh Sleep Quality Index

  Measured at screening and following 7 days of lithium administration (screening stage 2 and day 19)

• Munich Chronotype Questionnaire

  Measured at screening and following 7 days of lithium administration (screening Stage 2 and Day 19)

• General Health Questionnaire - 12

  Measured at screening and following 7 days of lithium administration (screening stage 2 and day 19).

Study Arms (1)

Single Group Assignment

EXPERIMENTAL

All participants will complete a no-lithium condition (control) followed by a lithium condition (intervention). During both conditions, visual and non-visual responses to controlled light exposure are assessed.

Drug: Lithium carbonate (Priadel); Other: Controlled light exposure

Interventions

Lithium carbonate (Priadel) DRUG

Oral lithium carbonate 600 mg daily for 7 days prior to the second laboratory assessment (and for both days while in the laboratory)

Single Group Assignment

Controlled light exposure OTHER

Participants undergo 90-minute dim light (\<1 lux) and light exposure (100-850 lux) conditions during laboratory assessments to evaluate visual and non-visual responses to light.

Single Group Assignment

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged between 18 and 40 years old
• Fluent in English (both spoken and written)
• Sleep duration between 6.5 and 9 hours daily
• Have a regular normal sleep schedule with bedtime (weekdays) between 21:30 and 01:00.
• BMI between 18 and 28kg/m2
• Currently enrolled and registered with a general practitioner
• Female participants only: should use effective contraception or refrain from engaging in sexual activity that could result in pregnancy during participation in the study.

You may not qualify if:

• History of psychiatric or neurological disorders
• First-degree family history of psychosis or severe mood disorder
• Current or past suicidal ideation or self-harm
• Current, chronic infections or diseases.
• Life-threatening allergies, specifically a nut allergy.
• Known visual disorders e.g., colour blindness, glaucoma, cataracts, diabetic retinopathy.
• Known medical conditions that could affect the conduct of the study including
• sleep disorders
• cancer
• diabetes
• anaemia
• epilepsy
• psoriasis
• thyroid disorders
• kidney disease

Sponsors & Collaborators

• Northumbria University: lead
• Newcastle University: collaborator
• Northumberland, Tyne and Wear NHS Foundation Trust: collaborator

Study Sites (1)

Northumbria University

Newcastle upon Tyne, Tyne & Wear, NE1 8SG, United Kingdom

Location

Related Publications (13)

• Zeitzer JM, Dijk DJ, Kronauer R, Brown E, Czeisler C; New Collective Author. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J Physiol. 2000 Aug 1;526 Pt 3(Pt 3):695-702. doi: 10.1111/j.1469-7793.2000.00695.x.

  PMID: 10922269 BACKGROUND

• Merikangas KR, Swendsen J, Hickie IB, Cui L, Shou H, Merikangas AK, Zhang J, Lamers F, Crainiceanu C, Volkow ND, Zipunnikov V. Real-time Mobile Monitoring of the Dynamic Associations Among Motor Activity, Energy, Mood, and Sleep in Adults With Bipolar Disorder. JAMA Psychiatry. 2019 Feb 1;76(2):190-198. doi: 10.1001/jamapsychiatry.2018.3546.

  PMID: 30540352 BACKGROUND

• Zisapel N. Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting. Cell Mol Neurobiol. 2001 Dec;21(6):605-16. doi: 10.1023/a:1015187601628.

  PMID: 12043836 BACKGROUND

• Freedman MS, Lucas RJ, Soni B, von Schantz M, Munoz M, David-Gray Z, Foster R. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science. 1999 Apr 16;284(5413):502-4. doi: 10.1126/science.284.5413.502.

  PMID: 10205061 BACKGROUND

• Czeisler CA, Shanahan TL, Klerman EB, Martens H, Brotman DJ, Emens JS, Klein T, Rizzo JF 3rd. Suppression of melatonin secretion in some blind patients by exposure to bright light. N Engl J Med. 1995 Jan 5;332(1):6-11. doi: 10.1056/NEJM199501053320102.

  PMID: 7990870 BACKGROUND

• Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Rosenthal NE. Manic-depressive patients may be supersensitive to light. Lancet. 1981 Feb 14;1(8216):383-4. doi: 10.1016/s0140-6736(81)91697-4. No abstract available.

  PMID: 6110011 BACKGROUND

• Ritter P, Soltmann B, Sauer C, Yakac A, Boekstaegers L, Reichard M, Koenitz K, Bauer M, Guldner H, Neumann S, Wieland F, Skene DJ. Supersensitivity of Patients With Bipolar I Disorder to Light-Induced Phase Delay by Narrow Bandwidth Blue Light. Biol Psychiatry Glob Open Sci. 2021 Jun 19;2(1):28-35. doi: 10.1016/j.bpsgos.2021.06.004. eCollection 2022 Jan.

  PMID: 36324599 BACKGROUND

• Malhi GS, Tanious M, Das P, Coulston CM, Berk M. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs. 2013 Feb;27(2):135-53. doi: 10.1007/s40263-013-0039-0.

  PMID: 23371914 BACKGROUND

• Alda M. Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry. 2015 Jun;20(6):661-70. doi: 10.1038/mp.2015.4. Epub 2015 Feb 17.

  PMID: 25687772 BACKGROUND

• Fountoulakis KN, Tohen M, Zarate CA Jr. Lithium treatment of Bipolar disorder in adults: A systematic review of randomized trials and meta-analyses. Eur Neuropsychopharmacol. 2022 Jan;54:100-115. doi: 10.1016/j.euroneuro.2021.10.003.

  PMID: 34980362 BACKGROUND

• Severus E, Taylor MJ, Sauer C, Pfennig A, Ritter P, Bauer M, Geddes JR. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord. 2014 Dec 20;2:15. doi: 10.1186/s40345-014-0015-8. eCollection 2014.

  PMID: 25530932 BACKGROUND

• McCarthy MJ, Gottlieb JF, Gonzalez R, McClung CA, Alloy LB, Cain S, Dulcis D, Etain B, Frey BN, Garbazza C, Ketchesin KD, Landgraf D, Lee HJ, Marie-Claire C, Nusslock R, Porcu A, Porter R, Ritter P, Scott J, Smith D, Swartz HA, Murray G. Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology. Bipolar Disord. 2022 May;24(3):232-263. doi: 10.1111/bdi.13165. Epub 2021 Dec 10.

  PMID: 34850507 BACKGROUND

• Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011 Mar;68(3):241-51. doi: 10.1001/archgenpsychiatry.2011.12.

  PMID: 21383262 BACKGROUND

Related Links

• Project Website

MeSH Terms

Conditions

Photophobia

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Central Study Contacts

Nayantara Santhi

CONTACT

0191 227 4055; nayantara.santhi@northumbria.ac.uk

Saranea Ganesan

CONTACT

+447587590262; saranea.g@northumbria.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Block design experiment with no lithium condition followed by lithium condition.

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: August 6, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: August 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)