Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression
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 d...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.740686/full |
| _version_ | 1819078904791433216 |
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| author | Francesco Benedetti Francesco Benedetti Sara Dallaspezia Sara Dallaspezia Elisa Maria Teresa Melloni Elisa Maria Teresa Melloni Cristina Lorenzi Raffaella Zanardi Raffaella Zanardi Barbara Barbini Barbara Barbini Cristina Colombo Cristina Colombo |
| author_facet | Francesco Benedetti Francesco Benedetti Sara Dallaspezia Sara Dallaspezia Elisa Maria Teresa Melloni Elisa Maria Teresa Melloni Cristina Lorenzi Raffaella Zanardi Raffaella Zanardi Barbara Barbini Barbara Barbini Cristina Colombo Cristina Colombo |
| author_sort | Francesco Benedetti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T19:20:30Z |
| format | Article |
| id | doaj.art-2ec9e4fb2b794c7d9f0811956c38ca31 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-21T19:20:30Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-2ec9e4fb2b794c7d9f0811956c38ca312022-12-21T18:52:58ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-09-011210.3389/fphys.2021.740686740686Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar DepressionFrancesco Benedetti0Francesco Benedetti1Sara Dallaspezia2Sara Dallaspezia3Elisa Maria Teresa Melloni4Elisa Maria Teresa Melloni5Cristina Lorenzi6Raffaella Zanardi7Raffaella Zanardi8Barbara Barbini9Barbara Barbini10Cristina Colombo11Cristina Colombo12Vita-Salute San Raffaele University, Milan, ItalyPsychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyPsychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyPsychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS Ospedale San Raffaele, Milan, ItalyPsychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyMood Disorders Unit, IRCCS Scientific Institute Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyMood Disorders Unit, IRCCS Scientific Institute Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyMood Disorders Unit, IRCCS Scientific Institute Ospedale San Raffaele, Milan, ItalyBackgroundMood 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.740686/fullchronotherapeuticssleep deprivationlight therapyinflammationinterleukin-1βantidepressant |
| spellingShingle | Francesco Benedetti Francesco Benedetti Sara Dallaspezia Sara Dallaspezia Elisa Maria Teresa Melloni Elisa Maria Teresa Melloni Cristina Lorenzi Raffaella Zanardi Raffaella Zanardi Barbara Barbini Barbara Barbini Cristina Colombo Cristina Colombo Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression Frontiers in Physiology chronotherapeutics sleep deprivation light therapy inflammation interleukin-1β antidepressant |
| title | Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression |
| title_full | Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression |
| title_fullStr | Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression |
| title_full_unstemmed | Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression |
| title_short | Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression |
| title_sort | effective antidepressant chronotherapeutics sleep deprivation and light therapy normalize the il 1β il 1ra ratio in bipolar depression |
| topic | chronotherapeutics sleep deprivation light therapy inflammation interleukin-1β antidepressant |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.740686/full |
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