Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression

Taler, Michal; Gil-Ad, Irit; Lomnitski, Liat; Korov, Inna; Baharav, Ehud; Bar, Meytal; Zolokov, Amichay; Weizman, Abraham

doi:10.1016/j.euroneuro.2007.03.010

Cited by 99 publications

(93 citation statements)

References 35 publications

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“…SSRIs appear to decrease the production of INFγ and stimulate the release of IL-10, by modulating the corresponding mRNA in immune cells [24] . Consistent with this, SSRIs also appear to upregulate the expression of genes involved in apoptotic pathways in T cells [25] . In addition, blockade of serotonin reuptake results in increased circulating serotonin levels, which have been reported to be able to suppress cytokine synthesis by T cells, B cells, natural killer cells and monocytes/macrophages [26][27][28][29] , resembling what occurs in sepsis after massive platelet degranulation [30] .…”

Section: Ssri-associated Cardiometabolic Risk: Molecular Pathwayssupporting

confidence: 60%

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

Chávez-Castillo¹,

Ortega²,

Nava³

et al. 2018

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Depression is one of the most common psychiatric disorders, and has become an epidemic in modern medical practice; notorious for frequently co-occurring with multiple comorbidities, especially cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and its various risk factors comprised in the metabolic syndrome (MS). Selective serotonin reuptake inhibitors (SSRIs) are the most widely used class of psychotropic drugs in this and many other clinical scenarios; yet their impact on cardiometabolic health has not been elucidated. The objective of this review was to summarize current views on the pharmacology of SSRIs and cardiometabolic risk, as well as available epidemiological evidence regarding its clinical significance. SSRIs appear to intervene in cardiometabolic physiology fundamentally by modulating chronic inflammation, a key pathophysiologic phenomenon in MS, DM2 and CVD. However, the dosing necessary to achieve a beneficial impact in this regard, as well as their clinical correlations, remain controversial. Each SSRI displays a particular profile regarding each of the components of the MS: weight gain seems to be the most common effect of SSRIs, more frequent with paroxetine, followed by citalopram and escitalopram. As a drug class, SSRIs also appear to promote hypercholesterolemia rather uniformly, while fluoxetine and citalopram appear to particularly increase triacylglyceride levels. In contrast, fluvoxamine and paroxetine seem to have the greatest impact on dysglycemia. Lastly, most SSRIs appear to be innocuous or even beneficial regarding blood pressure and high-density lipoprotein cholesterol. Nevertheless, many of these effects may vary significantly upon specific clinical circumstances, especially timing. This topic remains rather unexplored in clinical psychopharmacology, and further, larger-scale epidemiological studies are needed in order to offer improved care in this field.

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Section: Ssri-associated Cardiometabolic Risk: Molecular Pathwayssupporting

confidence: 60%

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

Chávez-Castillo¹,

Ortega²,

Nava³

et al. 2018

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“…However, sufficient evidence has suggested changes in the circulating levels of cytokines in depressed patients, which can be reversed by antidepressant treatments [11,12] .…”

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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“…Mice susceptible to stress-induced anhedonia show elevated expression of TNF-a and SERT in the prefrontal area (Couch et al 2013) and SSRIs inhibit the secretion of TNF-a in human T lymphocytes (Taler et al 2007). …”

Section: Tumor Necrosis Factor Alphamentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

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Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

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Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression

Cited by 99 publications

References 35 publications

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

Inflammation: a mechanism of depression?

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

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