Associated organisationsFlinders University · Massachusetts General Hospital · Monash University · The University of Melbourne · The University of SydneyEurope PMC affiliations are not treated as award recipients or mapped locations.
Funding£1.8M
PeriodNov 2023 — Sept 2029
In plain English
AI plain-English summary
Common antidepressants like SSRIs alter how the brain responds to light, and this effect on the body’s circadian clock may be the key to why they work—or why they sometimes fail. The problem is that despite decades of use, no one knows exactly how SSRIs lift mood. This project tests a specific, testable idea: that SSRIs work by making the brain more sensitive to light’s mood-boosting effects during the day, but that this same sensitivity leaves patients vulnerable to sleep disruption from light at night. The balance between these positive and negative effects may determine whether a given patient improves. If the hypothesis holds, it would transform how depression is treated. Clinicians could measure a patient’s baseline circadian traits—such as their melatonin suppression response to light or their sleep regularity—to predict whether an SSRI will help them. It could also lead to simple, practical changes: advising patients to get more morning light, avoid bright screens at night, or time their medication differently. This is fundamental science with a direct path to everyday clinical practice.
View original technical description
Despite being among the most commonly prescribed medications, the mechanism of action for antidepressants remains unknown. Our hypothesis is that selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed class of antidepressants, are effective due to effects on circadian function. We have shown that SSRIs amplify the non-visual effects of light. This potentially results in increased mood-elevating effect of light, but also an increased vulnerability to sleep and circadian disruption by light at night. We propose to investigate how SSRI efficacy may be due to an individual's balance of these positive and negative effects. Our comprehensive sleep and circadian phenotyping study will address the following aims: - What is the effect of chronic SSRI use on multiple measures of non-visual light sensitivity (including melatonin suppression, phase shifting, fMRI-measured responses to light, pupillary light responses), and common markers of circadian function (circadian phase, amplitude)? - Test the hypothesis that increased light sensitivity is predictive of better SSRI treatment efficacy for depression. - Test the hypothesis that sleep regularity and light-dark patterns interact with changes in light sensitivity to predict SSRI treatment efficacy for depression. - Are there baseline circadian characteristics (circadian phase, amplitude, markers of light sensitivity, genetics) that can predict better SSRI treatment efficacy?
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