Higher baseline interleukin-1β and TNF-α hamper antidepressant response in major depressive disorder

Benedetti, Francesco; Poletti, Sara; Vai, Benedetta; Mazza, Mario Gennaro; Lorenzi, Cristina; Brioschi, S.; Aggio, Veronica; Branchi, Igor; Colombo, Cristina; Furlan, Roberto; Zanardi, Raffaella

doi:10.1016/j.euroneuro.2020.11.009

Cited by 30 publications

(15 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the prevalence of depression is higher among patients suffering from immune-mediated inflammatory disorders ( 10 ), and immunomodulation improves their depressive symptomatology irrespective of their effects on physical illness ( 11 ). Increased inflammatory markers have also been associated with specific subgroups of depressed patients, particularly those responding poorly to conventional antidepressants ( 12 , 13 ), and those with high levels of anxiety ( 14 ), sleep disturbance ( 15 ), anhedonia ( 16 ), and psychomotor retardation ( 17 , 18 ) — a cluster of symptoms that have been referred to as “depressive-inflammatory.” Therefore, targeting inflammation in depression may be a viable treatment strategy, and recent meta-analyses have described encouraging effects of anti-inflammatory agents as adjunctive treatments in depressed patients ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

View full text Add to dashboard Cite

Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

show abstract

Section: Introductionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Considering the sample size, and given that distributions in patients before/after treatment and in HC were expected to be non-normal ( Arteaga-Henriquez et al, 2019 ; Benedetti et al, 2021 ), and to differ in variance but having at the most only a small difference in location ( Shields, 2020 ), IL-1β:IL1ra ratio values were compared between groups with simple non-parametric testing (Wald-Wolfowitz Runs Test and Wilcoxon Matched Pairs Test as appropriate). Homogeneity of variances was tested with Levene’s test.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…The immune state of patients affected by a depressive episode during major depressive disorder (MDD) or bipolar disorder (BD) is likely to play a role both, in the pathogenesis of depression, and as a determinant of therapy outcome ( Benedetti et al, 2020 ; Branchi et al, 2021 ). Raised pro-inflammatory cytokines in peripheral blood of patients with mood disorders parallel low-grade inflammation and glutamatergic dysfunction in the brain ( Haarman et al, 2016 ; Haroon et al, 2016 ; Franzen et al, 2020 ), and characterize subtypes of depression which are poor responsive to antidepressant drugs ( Arteaga-Henriquez et al, 2019 ; Benedetti et al, 2021 ), and progress toward gray and white matter pathology ( Haroon et al, 2017 ; Sugimoto et al, 2018 ; Green et al, 2021 ) and cognitive impairment ( Haroon and Miller, 2017 ; Misiak et al, 2018 ). Possibly as a result of this global deterioration of functioning and resulting hopelessness, immune dysfunction was consistently associated with suicidality independent of the underlying psychiatric diagnosis ( Steiner et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…To test the effect of TSD+LT on peripheral inflammatory markers associates with treatment resistant depression, in a proof-of-concept study here we studied Interleukin-1β (IL-1β), which has been consistently associated with non-response to drugs ( Arteaga-Henriquez et al, 2019 ; Benedetti et al, 2021 ). A key mediator of the inflammatory response, IL1β exists in balance with its receptor antagonist (IL1ra), it is widely expressed in the brain where it can decrease hippocampal neurogenesis also mediating the inhibitory effects of stress and inducing depressive-like symptoms ( Yoshimura et al, 2013 ; Yang et al, 2015 ), and associates with reduced functional connectivity within the cortico-striatal reward circuitry in unmedicated depressed patients ( Gupta et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Interaction effect between childhood abuse and interleukin-1β levels on suicidality in depressed patients

Lee

Jhon

Kim

et al. 2022

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

Higher baseline interleukin-1β and TNF-α hamper antidepressant response in major depressive disorder

Cited by 30 publications

References 50 publications

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

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

Interaction effect between childhood abuse and interleukin-1β levels on suicidality in depressed patients

Contact Info

Product

Resources

About