Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression

Yoshimura, Reiji; Hori, Hikaru; Ikenouchi-Sugita, Atsuko; Umene-Nakano, Wakako; Ueda, Nobuhisa; Nakamura, Jun

doi:10.1016/j.pnpbp.2009.03.020

Cited by 194 publications

(155 citation statements)

References 38 publications

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“…The peripheral levels of IL-6, TNF-α, and IL-1β are increased in patients with depression [13][14][15][16][17] , and antidepressant treatments reverse this effect [18][19][20] . These consistent results demonstrate that IL-6, TNF-α, and IL-1β are putative biomarkers for depression.…”

Section: Infl Ammatory Biomarkers Of Depressionmentioning

confidence: 99%

Inflammation: a mechanism of depression?

Han

2014

Neurosci. Bull.

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In recent decades, major depression has become more prevalent and research has shown that immune activation and cytokine production may be involved. This review is mainly focused on the contribution of infl ammation to depression. We fi rst briefl y introduce the infl ammatory biomarkers of depression, then discuss the sources of cytokines in the brain, and fi nally describe the neuroimmunological mechanisms underlying the association between infl ammation and depression.Keywords: depression; infl ammation; cytokines; hypothalamic-pituitary-adrenal axis; 5-HT; neuroplasticity ·Review· IntroductionThe prevalence of major depression has increased dramatically over the past few decades [1] , and women are nearly twice as likely as men to develop depressive disorder [2] . Depression is classified as a brain disorder, but its symptomatology includes some behaviors that also occur during chronic infl ammatory stress [3] . Research has shown that immune activation and the production of cytokines may be involved in depression [4] , so this relationship has received much attention. In fact, three causal pathways have been proposed: depression to inflammation, inflammation to depression, and a bidirectional relationship [5] . In this review, we focus on the impact of inflammation on depression and the underlying mechanisms. Cytokines are small cell-signaling proteins that mediate and regulate immune responses and inflammation, and can be divided into two categories:the pro-inflammatory cytokines interleukin (IL)-1 β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokines IL-1Rα, IL-4, IL-10, and transforming growth factor (TGF)-β1. Generally, t he proinfl ammatory cytokines promote systemic infl ammation and are essential for the initiation of an infl ammatory response to disease [6] , while the anti-inflammatory cytokines antagonize these actions to reduce inflammation and promote healing [6,7] . Moreover, some cytokines play dual roles [8] . In the central nervous system (CNS), the cellular source, function, and mechanisms of action of cytokines differ from those in the periphery. In the following, we briefl y introduce the current research on infl ammatory biomarkers of depression. Infl ammatory Biomarkers of DepressionSo far, there are neither universally accepted or defi nitive biomarkers of depression [9] , nor effective methods to assess the severity, endophenotypes, or response to treatment [10] .However, sufficient evidence has suggested changes in the circulating levels of cytokines in depressed patients, which can be reversed by antidepressant treatments [11,12] .So, many studies have aimed to clarify the neurobiological changes in depression and to establish inflammatory biomarkers. The peripheral levels of IL-6, TNF-α, and IL-1β are increased in patients with depression [13][14][15][16][17] , and antidepressant treatments reverse this effect [18][19][20] . These consistent results demonstrate that IL-6, TNF-α, and IL-1β are putative biomarkers for depression. However, due to the he...

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Section: Infl Ammatory Biomarkers Of Depressionmentioning

confidence: 99%

Inflammation: a mechanism of depression?

Han

2014

Neurosci. Bull.

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“…An investigation on patients with rapid-cycling bipolar disorder also showed that obesity was associated with a poorer treatment response to lithium and valproate (Kemp et al, 2010). Inflammation and increased pro-inflammatory cytokine production, commonly observed in obesity, are also associated with a poor antidepressant treatment response (Eller et al, 2008, O'Brien et al, 2007, Yoshimura et al, 2009. No studies have been identified investigating the effect of obesity on psychological and other non-drug treatments for psychiatric disorders.…”

Section: What Effect Does Obesity Have On Treatment Outcomes?mentioning

confidence: 99%

Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment

Lopresti

Drummond

2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

193

128

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Rates of obesity are higher than normal across a range of psychiatric disorders, including major depressive disorder, bipolar disorder, schizophrenia and anxiety disorders. While the problem of obesity is generally acknowledged in mental health research and treatment, an understanding of their bi-directional relationship is still developing. In this review the association between obesity and psychiatric disorders is summarised, with a specific emphasis on similarities in their disturbed biological pathways; namely neurotransmitter imbalances, hypothalamus-pituitary-adrenal axis disturbances, dysregulated inflammatory pathways, increased oxidative and nitrosative stress, mitochondrial disturbances, and neuroprogression. The applicability and effectiveness of weight-loss interventions in psychiatric populations is reviewed along with their potential efficacy in ameliorating disturbed biological pathways, particularly those mediating inflammation and oxidative stress. It is proposed that weight loss may not only be an effective intervention to enhance physical health but may also improve mental health outcomes and slow the rate of neuroprogressive disturbances in psychiatric disorders. Areas of future research to help expand our understanding of the relationship between obesity and psychiatric disorders are also outlined.

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“…Indeed, treatment with SSRIs has been shown to decrease MD associated cytokine elevations. In particular, the levels of inflammatory cytokines IL-1β, IL-6 and TNFα have been reported to be reduced following SSRI treatment (Basterzi et al, 2005;Kagaya et al, 2001;Lanquillon et al, 2000;Leo et al, 2006;Tuglu et al, 2003;Yoshimura et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

“…Indeed, though many studies showed that antidepressants have anti-inflammatory effects (Basterzi et al, 2005;Kagaya et al, 2001;Lanquillon et al, 2000;Leo et al, 2006;Tuglu et al, 2003;Yoshimura et al, 2009), an increasing number of studies are reporting a proinflammatory action (Chen et al, 2010;Haastrup et al, 2012;Hannestad et al, 2011;Jazayeri et al, 2010;Kim et al, 2013;Song et al, 2009). In addition, the bi-directional crosstalk between SSRI administration and inflammation has been described also by studies investigating the effects of antiinflammatory drugs on antidepressant efficacy.…”

mentioning

confidence: 99%

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Alboni

Poggini

Garofalo

et al. 2016

Brain, Behavior, and Immunity

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It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti-or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti-and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions. AbstractIt has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these drugs act either as anti-or proinflammatory. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21 days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti-and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that...

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Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression

Cited by 194 publications

References 38 publications

Inflammation: a mechanism of depression?

Inflammation: a mechanism of depression?

Obesity and psychiatric disorders: Commonalities in dysregulated biological pathways and their implications for treatment

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

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