IL-6 levels decrease with SSRI treatment in patients with major depression

Başterzi, Ayşe Devrim; Aydemir, Çiğdem; Kısa, Cebrail; Aksaray, Sebahat; Tüzer, Verda; Yazıcı, Kemal Utku; Göka, Erol

doi:10.1002/hup.717

Cited by 206 publications

(121 citation statements)

References 24 publications

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“…2004; Dunn et al, 2005;Castanon et al, 2002;Sluzewska et al, 1996;Basterzi et al, 2005). These results imply that depression could be a low-grade systemic inflammatory condition.…”

mentioning

confidence: 86%

Vagus Nerve Stimulation, Depression, and Inflammation

Das

2007

Neuropsychopharmacol

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“…2004; Dunn et al, 2005;Castanon et al, 2002;Sluzewska et al, 1996;Basterzi et al, 2005). These results imply that depression could be a low-grade systemic inflammatory condition.…”

mentioning

confidence: 86%

Vagus Nerve Stimulation, Depression, and Inflammation

Das

2007

Neuropsychopharmacol

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“…133 Sacre et al 134 reported that fluoxetine and citalopram reduced inflammation by inhibiting TLR function. Elevated cytokine levels in depressed patients have also been shown to normalize following SSRI treatment; 135,136 however, normalization of cytokine levels appears not to occur in patients that did not respond to SSRIs, 137 raising the possibility that immune system status could be a useful biomarker in structuring personalized depression therapies. Since T cells appear not to express SERT 47 (though note the caveat mentioned regarding T cell subtypes above), they do express 5-HT receptors 47 and thus the effects of SSRIs in vivo may also be indirect.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

Baganz

Blakely

2012

ACS Chem. Neurosci.

277

239

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Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions. Following a brief primer on the immune system, we describe our current understanding of the synthesis, release, and actions of 5-HT in modulating immune function, including the expression of 5-HT biosynthetic enzymes, receptors, and transporters that are typically studied with respect to the roles in the CNS. We then orient our presentation to recent findings that pro-inflammatory cytokines can modulate CNS 5-HT signaling, leading to a conceptualization that among the many roles of 5-HT in the body is an integrated physiological and behavioral response to inflammatory events and pathogens. From this perspective, altered 5-HT/immune conversations are likely to contribute to risk for neurobehavioral disorders historically linked to compromised 5-HT function or ameliorated by 5-HT targeted medications, including depression and anxiety disorders, obsessive-compulsive disorder (OCD), and autism. Our review raises the question as to whether genetic variation impacting 5-HT signaling genes may contribute to maladaptive behavior as much through perturbed immune system modulation as through altered brain mechanisms. Conversely, targeting the immune system for therapeutic development may provide an important opportunity to treat mental illness.

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“…195 In microglial and in mixed glial cultures, amitriptylin and nortriptylin were observed to inhibit the release of IL-1b and TNF-a. 196 Regarding the serum levels of MD patients, several researchers reported a decrease of IL-6 during treatment with serotonin re-uptake inhibitors 197,198 and other antidepressants. 101 Myint et al 85 reported an increase of the regulating, anti-inflammatory Th3-cytokine TGF-b together with a reduction of the IFN-g/IL-4 ratio after antidepressant therapy.…”

Section: Antidepressant Pharmacotherapymentioning

confidence: 99%

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

2007

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Beside the well-known deficiency in serotonergic neurotransmission as pathophysiological correlate of major depression (MD), recent evidence points to a pivotal role of increased glutamate receptor activation as well. However, cause and interaction of these neurotransmitter alterations are not understood. In this review, we present a hypothesis integrating current concepts of neurotransmission and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on immunological alterations and alterations in brain morphology in MD. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2, interferon-c, or tumor necrosis factor-a activate the tryptophan-and serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states during inflammatory somatic disorders are also associated with increased proinflammatory cytokines and increased consumption of tryptophan via activation of IDO. An enhanced consumption of serotonin and its precursor tryptophan through IDO activation could well explain the reduced availability of serotonergic neurotransmission in MD. An increased activation of IDO and its subsequent enzyme kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an enhanced production of quinolinic acid, a strong agonist of the glutamatergic N-methyl-D-aspartate receptor. In inflammatory states of the central nervous system, IDO is mainly activated in microglial cells, which preferentially metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas astrocytes -counteracting this metabolism due to the lack of an enzyme of this metabolism -have been observed to be reduced in MD. Therefore the type 1/type 2 immune response imbalance, associated with an astrocyte/microglia imbalance, leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are further strongly involved in re-uptake and metabolic conversion of glutamate. The reduced number of astrocytes could contribute to both, a diminished counterregulation of IDO activity in microglia and an altered glutamatergic neurotransmission. Further search for antidepressant agents should take into account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might exert antidepressant effects by acting on serotonergic deficiency, glutamatergic hyperfunction and antagonizing neurotoxic effects of quinolinic acid. Molecular Psychiatry (2007) 12, 988-1000; doi:10.1038/sj.mp.4002006; published online 24 April 2007 Keywords: major depression; psychoneuroimmunology; IDO; glutamate; immune system; serotonin Glutamate in depressionGlutamatergic neurotransmission is involved in depression and interacts with the serotonergic and noradrenergic systems The common therapeutic mechanism of antidepressant drugs is the enhancement of serotonergic and/or noradrenergic neurotransmission. On the basis of this pharmacological profile of antidepressant drugs, neurochemical research on major depression ...

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IL-6 levels decrease with SSRI treatment in patients with major depression

Abstract: The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system.

Cited by 206 publications

References 24 publications

Vagus Nerve Stimulation, Depression, and Inflammation

Vagus Nerve Stimulation, Depression, and Inflammation

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

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