Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1 beta:IL-1ra Ratio in Bipolar Depression

Background: Mood disorders associate with peripheral markers of low-grade inflammation, among which circulating levels of interleukin-1 beta (IL-1 beta) consistently predict diagnosis and poor outcomes. Antidepressant chronotherapeutics (total sleep deprivation and light therapy, TSD+LT) prompts response in drug-resistant bipolar depression, but its effect on peripheral inflammation were never assessed. Here we explored the effects of TSD+LT on IL-1 beta signaling. Methods: We studied the ratio between IL-1 beta and its receptor antagonist (IL-1 beta:IL1ra) in 33 healthy participants, and in 26 inpatients with a major depressive episode in course of Bipolar Disorder, before and after treatment with three cycles of repeated TSD+LT, interspersed with sleep recovery nights, administered during 1 week. Treatment effects of mood and on IL-1 beta:IL1ra were analyzed in the context of the Generalized Linear Model (GLM). Results: At baseline, patients had higher IL-1 beta, IL1ra, and IL-1 beta:IL1ra than controls. Treatment significantly decreased IL-1 beta:IL1ra, by decreasing IL-1 beta and increasing IL1ra, the effect being proportional to baseline levels and normalizing values. Patients with higher baseline levels showed the highest decrease in IL-1 beta:IL-1ra, which associated with the immediate antidepressant response at the first cycle; while patients with lower baseline values showed negligible changes in the IL-1 beta:IL-1ra, unrelated to treatment response. Conclusion: We observed a parallel change of inflammatory biomarkers and severity of depression after chronotherapeutics, suggesting that a reduction in inflammation associated with depression could contribute to the mechanism of action of TSD+LT, and warranting interest for controlled studies addressing the role of inflammation in the recovery from bipolar depression.

Automated summary

The study found that the TSD+LT treatment could decrease peripheral inflammation levels in patients with Bipolar Disorder, leading to antidepressant effects. The reduction in inflammatory biomarkers correlated with the severity of depression, suggesting a potential mechanism for the therapeutic action of TSD+LT.