Decreased sensitivity of the circadian system to light in current, but not remitted depression.

BACKGROUND: Misalignment of circadian timing in patients with depression has commonly been reported, but the underlying mechanisms are not known. Individual differences in the sensitivity of the circadian system to light affect how the biological clock synchronizes with the external environment and can lead to misalignment of rhythms. We investigated the sensitivity of the circadian system to light in unmedicated (for >3 months) women with a current or previous diagnosis of major depression, and healthy controls. METHODS: Baseline melatonin levels in dim light (<1 lux) were assessed, followed by melatonin levels in normal indoor lighting of 100 lux in order to determine melatonin suppression. RESULTS: Patients currently experiencing a depressive episode showed significantly lower levels of melatonin suppression to light compared to remitted patients and controls, with large effect sizes. Remitted patients and controls showed similar suppression. LIMITATIONS: The relatively small sample, and lack of long-term, within subject assessments, make it difficult to determine the potential causal role of reduced light sensitivity in the development of circadian disruption. CONCLUSIONS: We conclude that hyposensitivity of the circadian system to light may contribute to circadian misalignment in patients with depression. Interventions that increase sensitivity to light or provide stronger light cues may assist in normalizing circadian clock function.

The SSRI citalopram increases the sensitivity of the human circadian system to light in an acute dose.

RATIONALE: Disturbances of the circadian system are common in depression. Though they typically subside when depression is treated with antidepressants, the mechanism by which this occurs is unknown. Despite being the most commonly prescribed class of antidepressants, the effect of selective serotonin reuptake inhibitors (SSRIs) on the human circadian clock is not well understood. OBJECTIVE: To examine the effect of the SSRI citalopram (30 mg) on the sensitivity of the human circadian system to light. METHODS: This study used a double-blind, placebo-controlled, within-subjects, crossover design. Participants completed two melatonin suppression assessments in room level light (~ 100 lx), taking either a single dose of citalopram 30 mg or a placebo at the beginning of each light exposure. Melatonin suppression was calculated by comparing placebo and citalopram light exposure conditions to a dim light baseline. RESULTS: A 47% increase in melatonin suppression was observed after administration of an acute dose of citalopram, with all participants showing more suppression after citalopram administration (large effect, d = 1.54). Further, melatonin onset occurred later under normal room light with citalopram compared to placebo. CONCLUSIONS: Increased sensitivity of the circadian system to light could assist in explaining some of the inter-individual variability in antidepressant treatment responses, as it is likely to assist in recovery in some patients, while causing further disruption for others.