Circadian mechanisms for selective serotonin reuptake inhibitor treatment responses

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Depression is a mental illness which is the leading cause of disease burden in middle-income and high-income countries. It is characterised by low mood (i.e., feeling sad or down), loss of interest in or pleasure from things that were previously enjoyable, changes in appetite or weight, fatigue and sleep disturbance, difficulties with different thinking skills, and suicidal thoughts or behaviours. Most people with depression (up to 90%) experience sleep problems, which often precede the onset of mood symptoms. Problems with the circadian system, or ‘body clock,’ can contribute to sleep problems, and may play a role in the development of depression. We have previously found that a single dose of citalopram (an antidepressant) increases the effect of light on the body clock in health persons. This may contribute to variability in treatment outcomes in patient with depression. For example, increased light sensitivity may be beneficial for patients who were previously insensitive to light, or for those who exhibit healthy light exposure patterns (as the positive effects would be enhanced). However, for patients with unhealthy light patterns, or who are already hypersensitive, increased sensitivity due to antidepressant treatment may lead to the exacerbation of symptoms. Here, we aim to investigate the effect of chronic citalopram use on the response of the circadian system to light. Our main outcomes are the suppression of melatonin (a sleep-related hormone) and pupillary markers of light responses.

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