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

Francesco Benedetti; Sara Dallaspezia; Elisa Maria Teresa Melloni; Cristina Lorenzi; Raffaella Zanardi; Barbara Barbini; Cristina Colombo

doi:10.3389/fphys.2021.740686

journal article Open Access Sep 01, 2021

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

Francesco Benedetti

Sara Dallaspezia Elisa Maria Teresa Melloni Cristina Lorenzi Raffaella Zanardi Barbara Barbini Cristina Colombo

Frontiers in Physiology Vol. 12 · Frontiers Media SA

View at Publisher Save 10.3389/fphys.2021.740686

Abstract

BackgroundMood disorders associate with peripheral markers of low-grade inflammation, among which circulating levels of interleukin-1β (IL-1β) 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-1β signaling.MethodsWe studied the ratio between IL-1β and its receptor antagonist (IL-1β: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-1β:IL1ra were analyzed in the context of the Generalized Linear Model (GLM).ResultsAt baseline, patients had higher IL-1β, IL1ra, and IL-1β:IL1ra than controls. Treatment significantly decreased IL-1β:IL1ra, by decreasing IL-1β and increasing IL1ra, the effect being proportional to baseline levels and normalizing values. Patients with higher baseline levels showed the highest decrease in IL-1β: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-1β:IL-1ra, unrelated to treatment response.ConclusionWe 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.

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Published: Sep 01, 2021
Vol/Issue: 12
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Authors

Elisa Maria Teresa Melloni

Cite This Article

Francesco Benedetti, Sara Dallaspezia, Elisa Maria Teresa Melloni, et al. (2021). Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.740686

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

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