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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
45
Oral lithium carbonate 600 mg daily for 7 days prior to the second laboratory assessment (and for both days while in the laboratory)
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.
Northumbria University
Newcastle upon Tyne, Tyne & Wear, United Kingdom
Plasma melatonin change in response to light stimulation
Difference in plasma melatonin suppression following light exposure between the no-lithium and lithium conditions.
Time frame: 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.
Time frame: Measured once following 9 days of lithium carbonate administration (Day 21)
Difference in colour vision post-light exposure between lithium and no-lithium conditions
To determine differences in the Cambridge Colour Test (CCT) for changes in colour vision between the lithium and placebo groups post light exposure
Time frame: 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
Hourly waking electroencephalography (EEG) data collected when the participant is awake in the lab will be compared between the lithium and no-lithium conditions. EEG data collected pre, post and during the 90-minute light exposure will be compared between the lithium and no-lithium conditions.
Time frame: 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
Difference in Pittsburgh Sleep Quality Index total score between the lithium and no-lithium conditions in healthy participants. The global score on ranges from 0 to 21, where higher scores represent poorer sleep quality.
Time frame: Measured at screening and following 7 days of lithium administration (screening stage 2 and day 19)
Munich Chronotype Questionnaire
Difference in Munich Chronotype Questionnaire(MCTQ) measures between the lithium and no-lithium conditions in healthy participants. Total score on the MCTQ ranges from 16 to 86, with 16 to 41 being the eveningness type, 42 to 58 being the intermediate type, and 59 to 86 being the morningness type.
Time frame: Measured at screening and following 7 days of lithium administration (screening Stage 2 and Day 19)
General Health Questionnaire - 12
Difference in General Health Questionnaire-12 (GHQ-12) total score between the lithium and no-lithium conditions in healthy participants. The responses to all items are summed up to a total score of 0 to 36, with higher scores indicating poorer health status.
Time frame: Measured at screening and following 7 days of lithium administration (screening stage 2 and day 19).
Karolinska Sleepiness Scale
Difference in Karolinska Sleepiness Scale scores following light exposure between the lithium and no-lithium conditions in healthy participants. The scores range from 1 (extremely alert) to 9 (very sleepy, fighting sleep), with higher scores indicating increased sleepiness.
Time frame: Measured during and immediately following the 90-minute light exposure session after 7 days in the no-lithium condition and after 7 days of lithium administration (days 9-11 and 19-21).
Psychomotor Vigilance Test
Difference in Psychomotor Vigilance Test (PVT) pre and post light exposure between the lithium and no-lithium conditions in healthy participants will be compared. Mean reaction time (RT), lapses (RT \> 500ms), and false starts (responses before stimulus or \<100 ms) will be analysed. A higher mean RT and a greater number of lapses on the task represent poorer alertness and performance.
Time frame: Measured immediately following the 90-minute light exposure session after 7 days in the no-lithium condition and after 7 days of lithium administration. (And hourly while awake in the laboratory) (Days 9-11 and 19-21)
Morningness-Eveningness Questionnaire
This task is a measure of chronotype. Difference in Morningness-Eveningness Questionnaire total score between the lithium and no-lithium conditions in healthy participants. The score on this task ranges from 16 to 86. A score of 16-41 represents an evening person. A score of 59-86 represents a morning person and a score of 42 to 58 represents an intermediate person.
Time frame: Measured at screening and following 7 days of lithium administration (screening stage 2 and day 19).
Reading the Mind in the Eyes
This task will help assess a person's ability to interpret the emotional state of others based solely on images of their eyes, essentially measuring their "Theory of Mind" (ToM) - the capacity to understand and attribute thoughts and feelings to others.
Time frame: This task will be implemented during the laboratory segment of the lithium and no-lithium condition. The task will be implemented hourly when the participant is awake in the laboratory. (Days 9-11 and Days 19-21)
Karolinska Drowsiness Test
Drowsiness will be assessed with EEG data when the Karolinska Drowsiness Test is implemented. The Alpha and Theta power density, the Alpha Attenuation Coefficient (AAC), and the Alpha-Theta power differences will be assessed and analysed.
Time frame: Days 9-11 and 19-21, hourly while awake and before/after the light exposure segments.
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